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Review
. 2023 Mar 6;3(3):CD012349.
doi: 10.1002/14651858.CD012349.pub3.

Interventions for improving adherence to iron chelation therapy in people with sickle cell disease or thalassaemia

Louise J Geneen  1 , Carolyn Dorée  1 , Lise J Estcourt  2
Affiliations
Review

Interventions for improving adherence to iron chelation therapy in people with sickle cell disease or thalassaemia

Louise J Geneen et al. Cochrane Database Syst Rev. .

Abstract

Background: Regularly transfused people with sickle cell disease (SCD) and people with thalassaemia are at risk of iron overload. Iron overload can lead to iron toxicity in vulnerable organs such as the heart, liver and endocrine glands, which can be prevented and treated with iron-chelating agents. The intensive demands and uncomfortable side effects of therapy can have a negative impact on daily activities and wellbeing, which may affect adherence.

Objectives: To identify and assess the effectiveness of different types of interventions (psychological and psychosocial, educational, medication interventions, or multi-component interventions) and interventions specific to different age groups, to improve adherence to iron chelation therapy compared to another listed intervention, or standard care in people with SCD or thalassaemia.

Search methods: We searched CENTRAL (Cochrane Library), MEDLINE, PubMed, Embase, CINAHL, PsycINFO, ProQuest Dissertations & Global Theses, Web of Science & Social Sciences Conference Proceedings Indexes and ongoing trial databases (13 December 2021). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register (1 August 2022).

Selection criteria: For trials comparing medications or medication changes, only randomised controlled trials (RCTs) were eligible for inclusion. For studies including psychological and psychosocial interventions, educational interventions, or multi-component interventions, non-randomised studies of interventions (NRSIs), controlled before-after studies, and interrupted time series studies with adherence as a primary outcome were also eligible for inclusion.

Data collection and analysis: For this update, two authors independently assessed trial eligibility and risk of bias, and extracted data. We assessed the certainty of the evidence using GRADE.

Main results: We included 19 RCTs and one NRSI published between 1997 and 2021. One trial assessed medication management, one assessed an education intervention (NRSI) and 18 RCTs were of medication interventions. Medications assessed were subcutaneous deferoxamine, and two oral chelating agents, deferiprone and deferasirox. We rated the certainty of evidence as very low to low across all outcomes identified in this review. Four trials measured quality of life (QoL) with validated instruments, but provided no analysable data and reported no difference in QoL. We identified nine comparisons of interest. 1. Deferiprone versus deferoxamine We are uncertain whether or not deferiprone affects adherence to iron chelation therapy (four RCTs, unpooled, very low-certainty evidence), all-cause mortality (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.18 to 1.21; 3 RCTs, 376 participants; very low-certainty evidence), or serious adverse events (SAEs) (RR 1.43, 95% CI 0.83 to 2.46; 1 RCT, 228 participants; very low-certainty evidence). Adherence was reported as "good", "high" or "excellent" by all seven trials, though the data could not be analysed formally: adherence ranged from 69% to 95% (deferiprone, mean 86.6%), and 71% to 93% (deferoxamine, mean 78.8%), based on five trials (474 participants) only. 2. Deferasirox versus deferoxamine We are uncertain whether or not deferasirox affects adherence to iron chelation therapy (three RCTs, unpooled, very low-certainty evidence), although medication adherence was high in all trials. We are uncertain whether or not there is any difference between the drug therapies in serious adverse events (SAEs) (SCD or thalassaemia) or all-cause mortality (thalassaemia). 3. Deferiprone versus deferasirox We are uncertain if there is a difference between oral deferiprone and deferasirox based on a single trial in children (average age 9 to 10 years) with any hereditary haemoglobinopathy in adherence, SAEs and all-cause mortality. 4. Deferasirox film-coated tablet (FCT) versus deferasirox dispersible tablet (DT) One RCT compared deferasirox in different tablet forms. There may be a preference for FCTs, shown through a trend for greater adherence (RR 1.10, 95% CI 0.99 to 1.22; 1 RCT, 88 participants), although medication adherence was high in both groups (FCT 92.9%; DT 85.3%). We are uncertain if there is a benefit in chelation-related AEs with FCTs. We are uncertain if there is a difference in the incidence of SAEs, all-cause mortality or sustained adherence. 5. Deferiprone and deferoxamine combined versus deferiprone alone We are uncertain if there is a difference in adherence, though reporting was usually narrative as triallists report it was "excellent" in both groups (three RCTs, unpooled). We are uncertain if there is a difference in the incidence of SAEs and all-cause mortality. 6. Deferiprone and deferoxamine combined versus deferoxamine alone We are uncertain if there is a difference in adherence (four RCTs), SAEs (none reported in the trial period) and all-cause mortality (no deaths reported in the trial period). There was high adherence in all trials. 7. Deferiprone and deferoxamine combined versus deferiprone and deferasirox combined There may be a difference in favour of deferiprone and deferasirox (combined) in rates of adherence (RR 0.84, 95% CI 0.72 to 0.99) (one RCT), although it was high (> 80%) in both groups. We are uncertain if there is a difference in SAEs, and no deaths were reported in the trial, so we cannot draw conclusions based on these data (one RCT). 8. Medication management versus standard care We are uncertain if there is a difference in QoL (one RCT), and we could not assess adherence due to a lack of reporting in the control group. 9. Education versus standard care One quasi-experimental (NRSI) study could not be analysed due to the severe baseline confounding.

Authors' conclusions: The medication comparisons included in this review had higher than average adherence rates not accounted for by differences in medication administration or side effects, though often follow-up was not good (high dropout over longer trials), with adherence based on a per protocol analysis. Participants may have been selected based on higher adherence to trial medications at baseline. Also, within the clinical trial context, there is increased attention and involvement of clinicians, thus high adherence rates may be an artefact of trial participation. Real-world, pragmatic trials in community and clinic settings are needed that examine both confirmed or unconfirmed adherence strategies that may increase adherence to iron chelation therapy. Due to lack of evidence this review cannot comment on intervention strategies for different age groups.

PubMed Disclaimer

Conflict of interest statement

Louise Geneen: none to declare.

Carolyn Doree: none to declare.

Lise Estcourt: declares her employment as a healthcare professional by NHS Blood and Transplant.

Figures

1
1
CFGD trials register: Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1: DFP versus DFO, Outcome 1: Adherence to iron chelation therapy (%, SD)
1.2
1.2. Analysis
Comparison 1: DFP versus DFO, Outcome 2: Total SAEs (from therapy, disease, non‐adherence)
1.3
1.3. Analysis
Comparison 1: DFP versus DFO, Outcome 3: Other SAEs (from therapy, disease, non‐adherence)
1.4
1.4. Analysis
Comparison 1: DFP versus DFO, Outcome 4: All‐cause mortality
1.5
1.5. Analysis
Comparison 1: DFP versus DFO, Outcome 5: Iron overload: defined as proportion of participants with serum ferritin ≥ 800 (µg/L)
1.6
1.6. Analysis
Comparison 1: DFP versus DFO, Outcome 6: Organ damage
1.7
1.7. Analysis
Comparison 1: DFP versus DFO, Outcome 7: AEs related to iron chelation
2.1
2.1. Analysis
Comparison 2: DFX versus DFO, Outcome 1: Adherence to iron chelation therapy (%, SD)
2.2
2.2. Analysis
Comparison 2: DFX versus DFO, Outcome 2: SAEs (thalassaemia)
2.3
2.3. Analysis
Comparison 2: DFX versus DFO, Outcome 3: SAEs (sickle cell disease)
2.4
2.4. Analysis
Comparison 2: DFX versus DFO, Outcome 4: All‐cause mortality (thalassaemia)
2.5
2.5. Analysis
Comparison 2: DFX versus DFO, Outcome 5: Proportion of participants with iron overload (thalassaemia)
2.6
2.6. Analysis
Comparison 2: DFX versus DFO, Outcome 6: Total AEs related to iron chelation ‐ (thalassaemia)
2.7
2.7. Analysis
Comparison 2: DFX versus DFO, Outcome 7: Other AEs related to iron chelation ‐ (thalassaemia)
2.8
2.8. Analysis
Comparison 2: DFX versus DFO, Outcome 8: Total AEs (thalassaemia)
2.9
2.9. Analysis
Comparison 2: DFX versus DFO, Outcome 9: Other AEs related to iron chelation (SCD)
3.1
3.1. Analysis
Comparison 3: DFP versus DFX, Outcome 1: Adherence to iron chelation (%, SD)
3.2
3.2. Analysis
Comparison 3: DFP versus DFX, Outcome 2: Total SAEs
3.3
3.3. Analysis
Comparison 3: DFP versus DFX, Outcome 3: SAE (chelation‐related) (n/N)
3.4
3.4. Analysis
Comparison 3: DFP versus DFX, Outcome 4: All‐cause mortality (n/N)
4.1
4.1. Analysis
Comparison 4: DFX film‐coated tablet versus DFX dispersible tablet, Outcome 1: Adherence to iron chelation therapy (n/N)
4.2
4.2. Analysis
Comparison 4: DFX film‐coated tablet versus DFX dispersible tablet, Outcome 2: Adherence to iron chelation therapy (%, SD)
4.3
4.3. Analysis
Comparison 4: DFX film‐coated tablet versus DFX dispersible tablet, Outcome 3: Incidence of SAEs
4.4
4.4. Analysis
Comparison 4: DFX film‐coated tablet versus DFX dispersible tablet, Outcome 4: All‐cause mortality
4.5
4.5. Analysis
Comparison 4: DFX film‐coated tablet versus DFX dispersible tablet, Outcome 5: Incidence of organ damage
4.6
4.6. Analysis
Comparison 4: DFX film‐coated tablet versus DFX dispersible tablet, Outcome 6: Total AEs related to iron chelation
4.7
4.7. Analysis
Comparison 4: DFX film‐coated tablet versus DFX dispersible tablet, Outcome 7: Other AEs related to iron chelation
5.1
5.1. Analysis
Comparison 5: DFP and DFO versus DFP, Outcome 1: Incidence of SAEs
5.2
5.2. Analysis
Comparison 5: DFP and DFO versus DFP, Outcome 2: All‐cause mortality
5.3
5.3. Analysis
Comparison 5: DFP and DFO versus DFP, Outcome 3: Incidence of chelation therapy‐related AEs
6.1
6.1. Analysis
Comparison 6: DFP and DFO versus DFO, Outcome 1: Other AEs related to iron chelation
7.1
7.1. Analysis
Comparison 7: DFP and DFX versus DFP and DFO, Outcome 1: Adherence to iron chelation therapy rates
7.2
7.2. Analysis
Comparison 7: DFP and DFX versus DFP and DFO, Outcome 2: Incidence of SAE
7.3
7.3. Analysis
Comparison 7: DFP and DFX versus DFP and DFO, Outcome 3: All‐cause mortality
7.4
7.4. Analysis
Comparison 7: DFP and DFX versus DFP and DFO, Outcome 4: Organ damage (serum creatinine (≥ 33%) above baseline on 2 consecutive occasions)
7.5
7.5. Analysis
Comparison 7: DFP and DFX versus DFP and DFO, Outcome 5: Total AEs related to iron chelation
7.6
7.6. Analysis
Comparison 7: DFP and DFX versus DFP and DFO, Outcome 6: Other AEs related to iron chelation
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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Maggio 2020 {published data only}
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Tanner 2007 {published data only}
    1. Tanner MA, Galanello R, Dessi C, Agus A, Smith GC, Westwood MA, et al. Improved endothelial function combined chelation therapy in thalassaemia major. Blood 2006;108(11):Abstract no. 1770.
    1. Tanner MA, Galanello R, Dessi C, Smith GC, Westwood MA, Agus A, et al. A randomized, placebo-controlled, double-blind trial of the effect of combined therapy with deferoxamine and deferiprone on myocardial iron in thalassemia major using cardiovascular magnetic resonance. Circulation 2007;115(14):1876-84. - PubMed
    1. Tanner MA, Galanello R, Dessi C, Smith GC, Westwood MA, Agus A, et al. The effect of combined therapy with deferoxamine and deferiprone on myocardial iron and endothelial function in thalassaemia major: a randomized controlled trials using cardiovascular magnetic resonance. Haematologica 2006;91(Suppl 1):191.
    1. Tanner MA, Galanello R, Dessi C, Westwood MA, Smith GC, Khan M, et al. A randomized, placebo controlled, double blind trial of the effect of combined therapy with deferoxamine and deferiprone on myocardial iron in thalassaemia major using cardiovascular magnetic resonance. Blood 2005;106(11 Pt 1):Abstract no. 3655. - PubMed
Vichinsky 2007 {published data only}
    1. Vichinsky E, Bernaudin F, Forni GL, Gardner R, Hassell K, Heeney MM, et al. Long-term safety and efficacy of deferasirox (Exjade) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease. British Journal of Haematology 2011;154(3):387-97. - PMC - PubMed
    1. Vichinsky E, Bernaudin F, Forni GL, Gardner R, Hassell KL, Heeney MM, et al. Long-term safety and efficacy of deferasirox (Exjade®) in transfused patients with sickle cell disease treated for up to 5 years. Blood 2011;118(21):Abstract no. 845. - PMC - PubMed
    1. Vichinsky E, Coates T, Thompson A, Bernaudin F, Lagrone D, Dong V, et al. Safety and efficacy of iron chelation therapy with deferasirox in patients with sickle cell disease (SCD): 3.5-year follow-up. In: 14th Congress of the European Haematology Association; Jun 4-7; Berlin, Germany. 2009.
    1. Vichinsky E, Coates T, Thompson AA, Bernaudin F, Rodriguez M, Rojkjaer L, et al. Deferasirox (Exjade®), the once-daily oral iron chelator, demonstrates safety and efficacy in patients with sickle cell disease (SCD): 3.5-year follow-up. Blood 2008;112(11):Abstract no. 1420.
    1. Vichinsky E, Coates T, Thompson AA, Bernaudin F, Rodriguez M, Rojkjaer L, et al. Deferasorix (Exjade®), the once-daily oral iron chelator, demonstrates safety and efficacy in patients with sickle cell disease (SCD): 3.5-year follow-up. In: 3rd Annual Sickle Cell Disease Research and Educational Symposium and Annual Sickle Cell Disease Scientific Meeting; Feb 18-20; Florida, USA. 2009. [ABSTRACT NO.: 225]

References to studies excluded from this review

Abu 2015 {published data only}
    1. Abu SO, Auda W, Kamhawy H, Al-Tonbary Y. Impact of educational programme regarding chelation therapy on the quality of life for B-thalassemia major children. Hematology 2015;20(5):297-303. - PubMed
Adibi 2012 {published data only}
    1. Adibi A, Shayganfar A, Moayedi BS, Gharagozloo M, Maraashi SM, Maracy M, et al. Therapeutic effects of deferoxamine and silymarin versus deferoxamine alone in beta-thalassemia major based on findings of liver MRI. Journal of Research in Medical Sciences 2012;17(1 Suppl 1):S73-8. [CFGD REGISTER: TH226]
Aftab 2017 {published data only}
    1. Aftab S, Kamran A, Hanif S, Murtaza G, Fatima N, Masqati NU. Comparison of the mean serum ferritin levels in thalassaemia major patients after giving deferasirox and deferoxamine. Annals Abbasi Shaheed Hospital & Karachi Medical & Dental College 2017;22(4):243-8.
Al Kloub 2014 {published data only}
    1. Al-Kloub MI, A Bed MA, Al Khawaldeh OA, Al Tawarah YM, Froelicher ES. Predictors of non-adherence to follow-up visits and deferasirox chelation therapy among Jordanian adolescents with thalassemia major. Pediatric Hematology and Oncology 2014;31(7):624-37. - PubMed
Al Kloub 2014a {published data only}
    1. Al-Kloub MI, Salameh TN, Froelicher ES. Impact of psychosocial status and disease knowledge on deferoxamine adherence among thalassaemia major adolescents. International Journal of Nursing Practice 2014;20(3):265-74. - PubMed
Allemang 2016 {published data only}
    1. Allemang B, Allan K, Johnson C, Cheong M, Cheung P, Odame I, et al. Comprehensive structured transition program with dedicated transition navigator reduced lost to follow-up and improved medication adherence in adolescents and young adults with sickle cell disease and thalassemia. Journal of Adolescent Health 2017;60(Suppl 1):S40-1. [DOI: 10.1016/j.jadohealth.2016.10.263] - DOI
    1. Allemang B, Allan K, Johnson C, Cheong M, Cheung P, Odame I, et al. Comprehensive structured transition program with dedicated transition navigator reduced lost to follow-up and improved medication adherence in sickle cell disease and thalassemia adolescents and young adults . Blood 2016;128(22):317.
Al‐Momen 2020 {published data only}
    1. Al-Momen H, Hussein HK, Al-Attar Z, Hussein MJ. Green tea influence on iron overload in thalassemia intermedia patients: a randomized controlled trial. F1000research 2020;9:1136. [CFGD REGISTER: TH222] - PMC - PubMed
Al Refaie 1995 {published data only}
    1. Al-Refaie FN, Hershko C, Hoffbrand AV, Kosaryan M, Olivier NF, Tondury P, et al. Results of long-term deferiprone (L1) therapy: a report by the International Study Group on Oral Iron Chelators. British Journal of Haematology 1995;91(1):224-9. - PubMed
Alvarez 2009 {published data only}
    1. Alvarez O, Rodriguez-Cortes H, Robinson N, Lewis N, Pow Sang CD, Lopez-Mitnik G, et al. Adherence to deferasirox in children and adolescents with sickle cell disease during 1-year of therapy. Journal of Pediatric Hematology/Oncology 2009;31(10):739-44. - PubMed
Anderson 2017 {published data only}
    1. Anderson LM. Adherence and Quality of Life in Pediatric Sickle Cell Disease: A Pilot Mobile Health Intervention [PhD thesis]. Vol. 10188954. Ann Arbor, Michigan, USA: ProQuest LLC, 2017.
Anderson 2018 {published data only}
    1. Anderson LM, Leonard S, Jonassaint J, Lunyera J, Bonner M, Shah N. Mobile health intervention for youth with sickle cell disease: Impact on adherence, disease knowledge, and quality of life. Pediatric Blood & Cancer 2018;65(8):e27081. [DOI: 10.1002/pbc.27081] - DOI - PubMed
Angelucci 2005 {published data only}
    1. Angelucci E, Turlin B, Canatan D, Mangiagli A, De Sanctis V, Meddeb B, et al. Iron chelation therapy with deferasirox (Exjade (R), ICL670) or deferoxamine is effective in reducing iron overload in patients with advanced fibrosis and cirrhosis. Blood 2005;106(11 Pt 1):Abstract no: 2696. [CFGD REGISTER: TH73hh]
Ansari 2017 {published data only}
    1. Ansari S, Azarkeivan A, Miri-Aliabad G, Yousefian S, Rostami T. Comparison of iron chelation effects of deferoxamine, deferasirox, and combination of deferoxamine and deferiprone on liver and cardiac T2* MRI in thalassemia maior. Caspian Journal of Internal Medicine 2017;8(3):159-64. [CENTRAL: CN-01994996] [CFGD REGISTER: TH189] [EMBASE: 617257760] [PMID: ] - PMC - PubMed
Arian 2018 {published data only}
    1. Arian M, Memarian R, Oghazian MB, Vakilian F, Badiee Z. The effect of a holistic care program on the reduction of iron over load in patients with beta-thalassemia major: a randomized clinical trial. Iranian Red Crescent Medical Journal 2018;20(4):e60820. [DOI: 10.5812/ircmj.60820] - DOI
Armstrong 2011 {published data only}
    1. Armstrong EP, Skrepnek GH, Ballas SK, Kwok P, Snodgrass S, Sasane M. Costs, persistence, and hospitalizations associated with the use of iron-chelating therapies in sickle cell disease in medicaid patients. Blood 2011;118(21):3152. [DOI: 10.1182/blood.V118.21.3152.3152] - DOI
Aydinok 2016 {published data only}
    1. Aydinok Y, Delebe M, Basol G, Bayraktaroglu S, Karadas N, Barutcuoglu B, et al. A randomised 1 year study evaluating the impact of vitamin c supplementation on systemic iron parameters of iron overload in thalassemia major patients on long-term treatment with deferasirox. Blood 2016;128(22):Poster. [CENTRAL: CN-01335047] [CFGD REGISTER: TH174] [DOI: ] [EMBASE: 614248108]
Aziz 2021 {published data only}
    1. Aziz RA, Al Rafay S, Matter RM, El Hassan S. Impact of lifestyle modification module on adherence to therapeutic regimen of children and adolescents with beta thalassemia major. Medico-Legal Update 2021;21(2):956-65.
Bala 2014 {published data only}
    1. Bala J, Sarin J. Treatment adherence and quality of life of thalassemic children. International Journal of Nursing Education 2014;6(2):151-2.
Bartin Gooden 2015 {published data only}
    1. Barton-Gooden A, Grindley M, Knight-Madden J. Short-term impact of educational interventions on disease knowledge, illness perception and quality of life among Jamaican adolescents with sickle cell disease. West Indian Medical Journal 2015;64 (Suppl 2):Abstract no: 56.
Bazpour 2019 {published data only}
    1. Bazpour M, Gheibizadeh M, Malehi AS, Keikhaei B. The effect of a training program based on the PRECEDE-PROCEED model on lifestyle of adolescents with beta-thalassemia: a randomized controlled clinical trial. International Journal of Hematology-Oncology and Stem Cell Research 2019;13(1):12-9. [DOI: 10.18502/ijhoscr.v13i1.320] - DOI - PMC - PubMed
Belgrave 1989 {published data only}
    1. Belgrave FZ, Gilbert SK. Health care adherence of persons with sickle cell disease. The role of social support. Annals of the New York Academy of Sciences 1989;565:369-70.
Bellanti 2017 {published data only}
    1. Bellanti F, Del Vecchio GC, Putti MC, Maggio A, Filosa A, Cosmi C, et al. Population pharmacokinetics and dosing recommendations for the use of deferiprone in children younger than 6 years. British Journal of Clinical Pharmacology 2017;83(3):593-602. [CENTRAL: CN-01244545] [CFGD REGISTER: TH177a] [EMBASE: 613367569] - PMC - PubMed
Bellanti 2017a {published data only}
    1. Bellanti F, Di Iorio VL, Danhof M, Della Pasqua O. Sampling optimization in pharmacokinetic bridging studies: example of the use of deferiprone in children with beta-thalassemia. Journal of Clinical Pharmacology 2016;56(9):1094-103. [CENTRAL: CN-01402223] [CFGD REGISTER: TH177b] [PMID: ] - PubMed
Berkovitch 1995 {published data only}
    1. Berkovitch M, Davis S, Matsui D, Donsky J, Koren G, Olivieri NF. Use of a eutectic mixture of local anesthetics for prolonged subcutaneous drug administration. Journal of Clinical Pharmacology 1995;35(3):295-7. - PubMed
Biabani 2020 {published data only}
    1. Biabani A, Kermansaravi F, Navidian A. The effect of group education on adaptive behaviors and caregiver burden in mothers of children with thalassemia major: a trial clinical study. Medical-Surgical Nursing Journal 2020;9(1):1-8. [DOI: 10.5812/msnj.101560] - DOI
Bin Ahmed 2018 {published data only}
    1. Bin Ahmed H, Mehar SM, Rafi H. Comparison of thalassemia major adolescent cases when treated with deferasirox and deferoxamine in terms of mean level of ferritin serum. Indo American Journal of Pharmaceutical Sciences 2018;5(7):6627-32.
Canatan 2004 {published data only}
    1. Canatan D, Karadogan C, Balta N, Oguz N, Cosan R, Cengiz O, et al. Different desferrioxamine usage in the patients with thalassemia major: a cost-effect analysis. Turkish Journal of Haematology 2004;21(4):173-6. [CENTRAL: CN-01601124] [CFGD REGISTER: TH178] - PubMed
Cappellini 2005b {published data only}
    1. Cappellini MD, Bejaoui M, Agaoglu L, Canatan D, Capra M, Cohen A, et al. Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: efficacy and safety during 5 years' follow-up. Blood 2011;118(4):884-93. [CENTRAL: CN-00799637] [CFGD REGISTER: TH73ff] [PMID: ] - PubMed
Cappellini 2017 {published data only}
    1. Cappellini MD, Quebe-Fehling E, Pallaud C, Dieterle F, Porter JB. Exploring the clinical utility of renal safety biomarkers during iron chelation therapy in patients with beta-thalassemia and other anemias. In: Blood. Vol. 130. 2017:Suppl 1. [CFGD REGISTER: TH73kk] [DOI: ]
Chakrabarti 2013 {published data only}
    1. Chakrabarti P, Bohara V, Ray S, Sankar Ray S, Kumar, NU, Chaudhuri U. Can the availability of unrestricted financial support improve the quality of care of thalassemics in a center with limited resources? A single center study from India. Thalassemia Reports 2013;3(1):6-10.
Chaudhary 2021 {published data only}
    1. Chaudhary JL, Rathi SG, Shah S, Patel JT, Vaghela S. Deferiprone (Ferriprox) as newer iron chelator in thalassaemia major patients. Research Journal of Pharmacy and Technology 2021;14(2):1041-4.
Cheesman 2018 {published data only}
    1. Cheesman S, Shah R, Trompeter S, Eleftheriou P, Hylton B, Garbowski MW, et al. Real-world experience of switching from deferasirox dispersible to film-coated tablets: impact on adherence to chelation therapy, iron overload and renal function. Blood 2018;132(Suppl 1):132. [DOI: 10.1182/blood-2018-99-119030] - DOI
Daar 2010 {published data only}
    1. Daar S, Al, Salmi F, Ableen V, Jacob W, Jabeen Z, Pathare A. T2*MRI - An effective tool to increase chelation compliance in thalassemia major. Haematologica 2010;(95):698.
Darvishi‐Khezri 2017 {published data only}
    1. Darvishi-Khezri H, Salehifar E, Kosaryan M, Karami H, Alipour A, Shaki F, et al. The impact of silymarin on antioxidant and oxidative status in patients with beta-thalassemia major: a crossover, randomized controlled trial. Complementary Therapies in Medicine 2017;35:25-32. [CENTRAL: CN-01457968] [CFGD REGISTER: TH169a] [EMBASE: 618247195] [PMID: ] - PubMed
    1. Darvishi-Khezri H, Salehifar E, Kosaryan M, Karami H, Mahdavi M, Alipour A, et al. Iron-chelating effect of silymarin in patients with β-thalassemia major: a crossover randomised control trial. Phytotherapy Research : PTR 2018;32(3):496-503. [CENTRAL: CN-01603812] [CFGD REGISTER: TH169b] [EMBASE: 621031595] [PMID: ] - PubMed
Deugnier 2005 {published data only}
    1. Deugnier Y, Turlin B, Ropert M, Bejaoui M, Athanassiou-Metaxa M, Cario H, et al. Semi-quantitative assessment of hemosiderin distribution accurately reflects reductions in liver iron concentration following therapy with deferasirox (Exjade (R), ICL670) or deferoxamine in patients with transfusion-dependent anemia. Blood 2005;106(11 Pt 1):761A. [CFGD REGISTER: TH73ii]
Deugnier 2010 {published data only}
    1. Deugnier Y, Turlin B, Dong V, Giannone V, Zhang Y, Griffel L, Brissot P. Deferasirox improves liver pathology in beta-thalassemia patients with transfusional iron overload. Blood 2010;116(21):1734-5. [CFGD REGISTER: TH73gg]
Ding 2017 {published data only}
    1. Ding K. The Relationship between Adherence Behaviors and Health-related Quality of Life in Youth with Sickle Cell Disease: Does Cognitive and Academic Functioning Moderate This Relationship? [Masters thesis]. Ann Arbor, Michigan, USA: ProQuest Dissertations Publishing, 2017.
Elalfy 2016 {published data only}
    1. Elalfy M, Adly AA, Ismail E, Elalfy O. Efficacy and safety of vitamin C as an adjuvant to iron chelation therapy in young patients with b-thalassemia major: a randomized prospective trial. Haematologica 2015;100(Suppl 1):131. [ABSTRACT NO.: P376]
    1. Elalfy MS, Saber M, Adly A, Ismail E, Tarif M, Ibrahim F, Elalfy O. Role of vitamin C as an adjuvant therapy with different iron chelators in young beta-thalassemia major patients: safety and efficacy in relation to tissue Iron overload. Blood 2014;124(21):4046. [CFGD REGISTER: TH151c] - PubMed
    1. Elalfy MS, Saber MM, Adly AA, Ismail EA, Tarif M, Ibrahim F, et al. Role of vitamin C as an adjuvant therapy to different iron chelators in young beta-thalassemia major patients: efficacy and safety in relation to tissue iron overload. European Journal of Haematology 2016;96(3):318-26. [DOI: 10.1111/ejh.12594] - DOI - PubMed
Elalfy 2018 {published data only}
    1. Elalfy M, Helal B, Berdoukas V, Tricta F, Tarif M, Awad H, Adly A. Safety and efficacy of early start with suboptimal dose of deferiprone in minimally transfused infants with transfusion dependent thalassemia: a randomized trial. Haematologica 2017;102(138). [CFGD REGISTER: TH176c]
    1. Elalfy MS, Adly A, Awad H, Tarif Salam M, Berdoukas V, Tricta F. Safety and efficacy of early start of iron chelation therapy with deferiprone in young children newly diagnosed with transfusion-dependent thalassemia: a randomized controlled trial. American Journal of Hematology 2018;93(2):262-8. [DOI: 10.1002/ajh.24966] - DOI - PubMed
    1. Elalfy MS, Berdoukas V, Tricta F, Adly A, Hazza N, Awed H, et al. A randomized trial on the safety and efficacy of early start of iron chelation therapy with deferiprone in newly diagnosed children with transfusion dependent thalassemia. Blood 2016;128(22). [CENTRAL: CN-01335064] [CFGD REGISTER: TH176a] [EMBASE: 614248035]
    1. NCT02173951. An algorithm to start iron chelation in minimally transfused young beta-thalassemia major patients. clinicaltrials.gov/ct2/show/NCT02173951 (first received 25 June 2014).
Emami Zeydi 2018 {published data only}
    1. Emami Zeydi A, Karimi Moonaghi H, Heydari A. Psychological therapies: the missing link in improving treatment adherence in patients with beta-thalassemia major. Iranian Journal of Blood and Cancer (Iranian Pediatric Hematology and Oncology Society) 2018;9(4):130-1.
Eshghi 2018 {published data only}
    1. Eshghi P, Amin Asnafi A, Shamshiri A, Alavi S, Molavi M, Tamaddoni A, et al. The comparison of efficacy of original brand deferoxamine with generic iranian made deferoxamine in urinary iron excretion in patients with thalassemia major. Iranian Journal of Blood and Cancer (Iranian Pediatric Hematology and Oncology Society) 2018;9(4):108-11.
EUCTR 2007‐000766‐20‐IT {published data only}
    1. EUCTR 2007-000766-20-IT. A multicenter, randomized, open-label phase II trial evaluating deferasirox compared with deferoxamine in patients with cardiac iron overload due to chronic blood transfusions - ND. EUCTR2007-000766-20-IT (first received 11 April 2008).
EUCTR 2007‐004008‐10 {published data only}
    1. EUCTR 2007-004008-10. Evaluating the efficacy of Exjade® (deferasirox) in transfusion dependent chronic anaemias (myelodysplasia syndrome, beta-thalassaemia major patients) with chronic iron overload. clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-00... (first received 17 October 2007).
EUCTR 2015‐003225‐33‐GR {published data only}
    1. EUCTR 2015-003225-33-GR. A study to evaluate the benefit and safety of Luspatercept (ACE-536) in adults with beta-thalassemia who do not require regular red blood cell tranfusions. EUCTR2015-003225-33-GR (first received 27 October 2017).
Farhady 2020 {published data only}
    1. Farhady S, Sepehri MM, Pourfathollah AA. Evaluation of effective factors in the acceptance of mobile health technology using the unified theory of acceptance and use of technology (UTAUT), case study: blood transfusion complications in thalassemia patients. Medical Journal of the Islamic Republic of Iran 2020;34:83. - PMC - PubMed
Galanello 2006b {published data only}
    1. Galanello R, Piga A, Forni G L, Bertrand Y, Foschini M L, Bordone E, et al. Phase II clinical evaluation of deferasirox, a once-daily oral chelating agent, in pediatric patients with beta-thalassemia major. Haematologica 2006;91(10):1343-51. [URL: https://www.haematologica.org/article/view/4176] - PubMed
Gallo 2014 {published data only}
    1. Gallo AM, Wilkie DJ, Wang E, Labotka RJ, Molokie RE, Stahl C, et al. Evaluation of the SCKnowIQ tool and reproductive CHOICES intervention among young adults with sickle cell disease or sickle cell trait. Clinical Nursing Research 2014;23(4):421-41. [DOI: 10.1177/1054773813479377] - DOI - PMC - PubMed
Gomber 2004 {published data only}
    1. Gomber S, Saxena R, Madan N. Comparative efficacy of desferrioxamine, deferiprone and in combination on iron chelation in thalassemic children. Indian Pediatrics 2004;41(1):21-7. - PubMed
Gordon 2018 {published data only}
    1. Gordon P, Nagasubramanian R, Parker A, Clark L, Balmer H, Gordon C, et al. Novel multidisciplinary comprehensive clinic program improves patient compliance, patient satisfaction and health maintainance outcomes in the outpatient setting for patients with severe sickle cell disease. Blood 2018;132(Suppl 1):4937. [DOI: 10.1182/blood-2018-99-110112] - DOI
Habibian 2014 {published data only}
    1. Habibian N. Comparision of therapeutic effect of osveral & desferal in patients with thalassemia (Bahonar Hospital in Karaj 2012-2013). Iranian Journal of Pediatrics (Tehran University of Medical Sciences) 2014;24(S2):1.
Hagag 2013 {published data only}
    1. Hagag AA, Elfaragy MS, Elrifaey SM, Abd El-Lateef AE. Therapeutic value of combined therapy with deferiprone and silymarin as iron chelators in Egyptian children with beta thalassemia major. Infectious Disorders Drug Targets 2015;15(3):189-95. [CENTRAL: CN-01259022] [CFGD REGISTER: TH131b] [EMBASE: 2015510006] [PMID: ] - PubMed
Hamed 2020 {published data only}
    1. Hamed EM, Meabed MH, Hussein RRS, Aly UF. Recent insight on improving the iron chelation efficacy of deferasirox by adjuvant therapy in transfusion dependent beta thalassemia children with sluggish response. Expert Opinion on Drug Metabolism & Toxicology 2020;16(3):179-93. [CFGD REGISTER: TH223] - PubMed
Hankins 2020 {published data only}
    1. Hankins JS, Shah N. Tackling adherence in sickle cell disease with mHealth. Lancet Haematology 2020;7(10):e713-4. [DOI: 10.1016/S2352-3026(20)30299-4] - DOI - PubMed
Hankins 2021 {published data only}
    1. Hankins JS, Klesges LM. Bridging the implementation gap in medication adherence. If you build it, will they come? British Journal of Haematology 2021;196(1):17-8. [DOI: 10.1111/bjh.17953] - DOI - PubMed
Inusa 2022 {published data only}
    1. Inusa B, Hamdy M, El-Beshlawy A, Ebeid F, Kwiatkowski J, Kanter J, et al. Long-term efficacy and safety of deferiprone for patients with sickle cell disease or other anemias. Hemasphere 2022;6(1):8. [CFGD REGISTER: HM15b]
    1. Verissimo MP, Elalfy MS, Hamdy M, El-Beshlawy A, Ebeid F, Kanter J, et al. Long-term safety and efficacy of deferiprone for the treatment of chronically transfused, iron-overloaded patients with sickle cell disease or other anemias. Hematology, Transfusion and Cell Therapy 2021;43:S23-4. [CFGD REGISTER: HM15a]
IRCT 2009 0813002342N9 (Rafati 2022) {published data only}
    1. IRCT 2009 0813002342N9. The comparison of the efficacy of Iranian Deferasirox (Osveral®) and Exjade® on serum ferritin in patients with major beta-thalassemia. en.irct.ir/trial/33699 (first received 23 October 2018).
    1. Rafati M, Karami H, Lashtoo-Aghaee B, Lashtoo-Aghaee B, Dabirian M, Avan R. Two trade names of deferasirox (Osveral® and Exjade®) in reduction of iron overload parameters in major betathalassemia patients: a randomized open labeled clinical trial. Caspian Journal of Internal Medicine 2022;13(1):61-9. [CFGD REGISTER: TH225] - PMC - PubMed
IRCT 2015 012914504N3 {published data only}
    1. IRCT2015012914504N3. Effect of storytelling on social, excited and education self-efficacy in children 7-12 years old with thalassemia in Mashhad. trialsearch.who.int/Trial2.aspx?TrialID=IRCT2015012914504N3 (first received 23 February 2015).
IRCT 2016 041627412N1 {published data only}
    1. IRCT2016041627412N1. Treatment of iron overload in thalassemia patients: comparison of combined therapy with deferoxamine and deferiprone versus monotherapy with deferoxamine or deferiprone in iron overloaded thalassemia patients. www.irct.ir/trial/22446 (first received 4 May 2016).
IRCT 2017 0512033932N5 {published data only}
    1. IRCT20170512033932N5. The effect of positive thinking education on parents of adolescents with thalassemia. www.irct.ir/trial/32127 (first received 2 September 2018).
IRCT 2018 0207038655N1 {published data only}
    1. IRCT20180207038655N1 . The effect of mobile phone-based education on patients with thalassemia. https://www.irct.ir/trial/30609 (first received 15 May 2018).
Jhinger 2018 {published data only}
    1. Jhinger P, Sobti PC, Kaushal S, Kakkar S. Combination of two oral iron chelators in patients with thalassemia major. Pediatric Hematology Oncology Journal (Pediatric Hematology Oncology Chapter of Indian Academy of Pediatrics) 2018;3(3):55-8. [DOI: 10.1016/j.phoj.2018.08.001] - DOI
Kattamis 2018 {published data only}
    1. Kattamis A, Aydinok Y, Taher A. Optimising management of deferasirox therapy for patients with transfusion-dependent thalassaemia and lower-risk myelodysplastic syndromes. European Journal of Haematology 2018;101(3):272-82. [DOI: 10.1111/ejh.13111] - DOI - PubMed
Kattamis 2021 {published data only}
    1. Kattamis A, Badawy S, Ezzat H, Zhao F, Tricta F, Sheth S, et al. A multicenter open-label study on the safety and acceptability of twice-daily deferiprone tablets among patients with transfusion-dependent thalassemia and systemic iron overload. HemaSphere 2021;5(Suppl 2):634.
Kejriwal 2020 {published data only}
    1. Kejriwal SS. Establishing initial data and assessing the feasibility of a community collaborative to improve adherence to essential management in beta-thalassemia patients in Pune, India [PhD thesis]. Vol. 27832201. Ann Arbor, Michigan, USA: ProQuest Dissertations Publishing, 2020.
Kidson Gerber 2008 {published data only}
    1. Kidson-Gerber G, Lindeman R. Adherence to desferrioxamine and deferiprone and the impact of deferiprone co-prescription in thalassaemia major patients. Does the addition of deferiprone improve adherence? British Journal of Haematology 2008;142(4):679-80. - PubMed
Kolnagou 2008 {published data only}
    1. Kolnagou A, Economides C, Eracleous E, Kontoghiorghes GJ. Long term comparative studies in thalassemia patients treated with deferoxamine or a deferoxamine/deferiprone combination. Identification of effective chelation therapy protocols. Hemoglobin 2008;32(1-2):41-7. - PubMed
Kompany 2009 {published data only}
    1. Kompany F, Mohammadi S, Sigari N, Hadizadeh N, Rezaie N, Gharibi FS. Comparative efficacy of deferrioxamin and combination of deferiprone and deferrioxamine on echocardiographic indices in beta thalassemic patients. Scientific Journal of Kurdistan University of Medical Sciences 2009;14(2):21-30. [CENTRAL: CN-00802957] [CFGD REGISTER: TH190] [EMBASE: 359846802]
Leonard 2014 {published data only}
    1. Leonard S, Jonassaint J, Anderson L, Shah N. The use of mobile technology for intensive training in medication management in the pediatric population. Blood 2014;124(21).
Loiselle 2015 {published data only}
    1. Loiselle K, Lee JL, Szulczewski L, Drake S, Crosby LE, Pai AL. Systematic and meta-analytic review: medication adherence among pediatric patients with sickle cell disease. Journal of Pediatric Psychology 2015;41(4):406-18. [DOI: 10.1093/jpepsy/jsv084] - DOI - PMC - PubMed
Loiselle 2016 {published data only}
    1. Loiselle K, Lee JL, Szulczewski L, Drake S, Crosby LE, Pai AL. Systematic and meta-analytic review: medication adherence among pediatric patients with sickle cell disease. Journal of Pediatric Psychology 2016;41(4):406-18. - PMC - PubMed
Madmoli 2019 {published data only}
    1. Madmoli Y, Salimi M, Madmoli M, Maraghi E, Pelarak F, Korkini N, et al. The effect of Orem self-care model on health-related quality of life of patients with thalassemia major. Journal of Research in Medical and Dental Science 2019;7(2):170-6.
Matti 2013 {published data only}
    1. Matti M. Study on comparison of efficacy and adverse effects of deferasirox vs deferiprone in treatment of iron overload in thalassemia [PhD thesis]. Bengaluru, India: Rajiv Gandhi University of Health Sciences, 2013.
Mazzone 2009 {published data only}
    1. Mazzone L, Battaglia L, Andreozzi F, Romeo MA, Mazzone D. Emotional impact in beta-thalassaemia major children following cognitive-behavioural family therapy and quality of life of caregiving mothers. Clinical Practice and Epidemiology in Mental Health 2009;5(5):Online. [DOI: 10.1186/1745-0179-5-5] - DOI - PMC - PubMed
Mohamed Al Nasiri 2018 {published data only}
    1. Mohamed Al Nasiri YS. Parent Educational Intervention Program (PEIP) for Improving Parental Knowledge, Self-Efficacy, & Parent Perception of Health Related Quality of Life in Children with Sickle Cell Disease Using Smartphone Technology [PhD thesis]. Los Angeles, California, USA: UCLA Electronic Theses and Dissertations, 2018.
Mohammadi 2018 {published data only}
    1. Mohammadi E, Tamaddoni A, Qujeq D, Nasseri E, Zayeri F, Zand H, et al. An investigation of the effects of curcumin on iron overload, hepcidin level, and liver function in beta-thalassemia major patients: a double-blind randomized controlled clinical trial. Phytotherapy Research : PTR 2018;32(9):1828-35. [CENTRAL: CN-01655783] [CFGD REGISTER: TH181] [EMBASE: 622380786] [PMID: ] - PubMed
    1. Nasseri E, Mohammadi E, Tamaddoni A, Qujeq D, Zayeri F, Zand H. Benefits of curcumin supplementation on antioxidant status in beta-thalassemia major patients: a double-blind randomized controlled clinical trial. Annals of Nutrition & Metabolism 2017;71(3-4):136-44. [CFGD REGISTER: TH181b] - PubMed
Molavi 2013 {published data only}
    1. Molavi MA, Doozandeh H, Nazemi A, Evazi R, Mansoori F. Comparison of therapeutic response and complications of oral Osveral and injection Desfereal chelating agent in patient with thalassemia major. Asian Journal of Medical and Pharmaceutical Researches 2013;3(3):93-7.
Molavi 2014 {published data only}
    1. Molavi MA, Poor ST, Malesksabet M. Combined desferrioxamine (Desferal) and deferasirox in children. Advances in Biological Research 2014;8(4):171-5. [DOI: 10.5829/idosi.abr.2014.8.4.8546] - DOI
Molazem 2016 {published data only}
    1. Molazem Z, Noormohammadi R, Dokouhaki R, Zakerinia M, Bagheri Z. The effects of nutrition, exercise, and a praying program on reducing iron overload in patients with beta-thalassemia major: a randomized clinical trial. Iranian Journal of Pediatrics 2016;26(5):e3869. [DOI: 10.5812/ijp.3869] - DOI - PMC - PubMed
NCT00061750 {published data only}
    1. Cappellini MD, Cohen A, Piga A, Bejaoui M, Perrotta S, Agaoglu L, et al. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with β-thalassemia. Blood 2006;107(9):3455-62. [DOI: ] - PubMed
    1. Cohen AR, Glimm E, Porter JB. Effect of transfusional iron intake on response to chelation therapy in β-thalassemia major. Blood 2008;111(2):583-7. [DOI: ] - PubMed
    1. NCT00061750. Safety & efficacy of ICL670 vs. deferoxamine in beta-thalassemia patients with iron overload due to blood transfusions. https://clinicaltrials.gov/ct2/show/study/NCT00061750 First received 4 June 2003 (retrospective).
NCT01709032 {published data only}
    1. NCT01709032. Combination deferasirox and deferiprone for severe iron overload in thalassemia. clinicaltrials.gov/ct2/show/NCT01709032 (first received 17 October 2012).
NCT02133560 {published data only}
    1. NCT02133560. Use of mobile technology for intensive training in medication management. clinicaltrials.gov/ct2/show/NCT02133560 (first received 8 May 2014).
NCT02466555 {published data only}
    1. NCT02466555. Music therapy in sickle cell transition study. clinicaltrials.gov/ct2/show/NCT02466555 (first registered 9 June 2015).
NCT03233269 {published data only}
    1. NCT03233269. BEATS 2: music therapy in sickle cell. clinicaltrials.gov/ct2/show/NCT03233269 (first received 28 July 2017).
NCT03342404 {published data only}
    1. NCT03342404. A study to determine the efficacy and safety of luspatercept in adults with non transfusion dependent beta (β)-thalassemia. clinicaltrials.gov/show/NCT03342404 (first received 17 November 2017).
NCT03381833 {published data only}
    1. NCT03381833. A study with LJPC-401 for the treatment of myocardial iron overload in adult patients with transfusion-dependent beta thalassemia. clinicaltrials.gov/ct2/show/NCT03381833 (first received 22 December 2017).
NCT03591575 {published data only}
    1. Elalfy M, El-Beshlawy A, Adly A, Ebeid F, Fradette C, Lee D, et al. Safety and efficacy of early-start deferiprone in infants and young children with beta-thalassemia (START study). Hemasphere 2022;6(1):12-3. [CFGD REGISTER: TH224d]
    1. Elalfy MS, Adly A, Ebeid FS, El-Beshlawy A, Salama N, Hamdy M. A prospective randomized multicenter trial using either deferiprone or deferasirox after an early start of deferiprone or placebo in young children newly diagnosed with transfusion-dependent beta-thalassemia. Blood 2021;138:3071. [CFGD REGISTER: TH224b]
    1. Elalfy MS, El-Beshlawy A, Adly A, Ebeid FS, Fradette C, Lee D, et al. Safety and efficacy of early-start deferiprone in infants and young children with beta-thalassemia (START study). Blood 2021;138:3070. [CFGD REGISTER: TH224c]
    1. NCT03591575. Safety and efficacy of early treatment with deferiprone in infants and young children. clinicaltrials.gov/ct2/show/NCT03591575 (first received 19 July 2018).
NCT03637556 {published data only}
    1. NCT03637556. Pilot study to assess the safety, pk and iron chelating activity of DST-0509 (deferasirox) in thalassemia patients refractory to chelation. clinicaltrials.gov/ct2/show/NCT03637556 (first received 20 August 2018).
NCT04092205 {published data only}
    1. NCT04092205. Phase 2a pilot study of NBMI treatment in patients with beta thalassemia major, requiring iron chelation. clinicaltrials.gov/ct2/show/NCT04092205 (first received 17 September 2019).
NCT04292314 {published data only}
    1. NCT04292314. Hydroxy urea, omega 3, nigella sativa, honey on oxidative stress and iron chelation in pediatric major thalassemia. clinicaltrials.gov/ct2/show/NCT04292314 (first received 3 March 2020).
NCT04541875 {published data only}
    1. NCT04541875. Medication adherence and non-adherence in adults with rare disease. clinicaltrials.gov/ct2/show/NCT04541875 (first received 9 September 2020).
NCT04688411 {published data only}
    1. NCT04688411. An mHealth strategy to improve medication adherence in adolescents with sickle cell disease. clinicaltrials.gov/ct2/show/NCT04688411 (first received 24 December 2020).
Pakbaz 2005 {published data only}
    1. Pakbaz Z, Fischer R, Gamino R, Quirolo K, Yamashita R, Treadwell M, et al. Assessing compliance to iron chelation therapy in patients with thalassemia. Blood 2004;104(11):33B. [DOI: ]
    1. Pakbaz ZR, Fischer M, Treadwell R, Yamashita EB, Fung L, Calvell K, et al. A simple model to assess and improve adherence to iron chelation therapy with deferoxamine in patients with thalassemia. Annals of the New York Academy of Sciences 2005;1054:486-91. [DOI: ] [PMID: ] - PubMed
Pantalone 2011a {published data only}
    1. Vitrano A, Ruffo GB, Pepe A, D'Ascola DG, Caruso V, Filosa A, et al. Long-term sequential deferiprone and deferasirox therapy in transfusion-dependent thalassaemia patients: a prospective clinical trial. British Journal of Haematology 2019;186(6):e209-11. [CENTRAL: CN-02091994] [CFGD REGISTER: TH100j] [EMBASE: 628850981] [PMID: ] - PubMed
Patalia Abishek 2014 {published data only}
    1. Patalia Abishek Y, Kori VK, Patel KS, Rajagopala S. Efficacy of triphaladi avaleha on beejadushtijanya pandu (thalassemia). Ayu 2014;35(1):15-21. [CENTRAL: CN-01092429] [CFGD REGISTER: TH175] - PMC - PubMed
Peng 2013 {published data only}
    1. Peng P, Long LL, Huang ZK, Zhang L, Li XH, Feng X, et al. Comparison of deferasirox and deferoxamine treatment in iron-overloaded patients: liver iron concentration determined by quantitative MRI-R2*. Chinese Journal of Radiology 2013;47(1):55-9.
Porter 2012 {published data only}
    1. Porter J, Bowden DK, Economou M, Troncy J, Ganser A, Habr D, et al. Health- related quality of life, treatment satisfaction, adherence and persistence in beta-thalassemia and myelodysplastic syndrome patients with iron overload receiving deferasirox: results from the epic clinical trial. Anemia 2012;297:641. [DOI: ] - PMC - PubMed
    1. Porter JB, Athanasiou-Metaxa M, Bowden DK, Troncy J, Habr D, Domokos G, et al. Improved patient satisfaction, adherence and health-related quality of life with deferasirox (Exjade) in beta-thalassemia patients previously receiving other iron chelation therapies. Blood 2009;114(22):poster 2486. [DOI: ]
Safaei 2019 {published data only}
    1. Safaei S, Abedi H, Parand S, Karimi M. Evaluation of the effect of support-training system of peer group on promotion of self-care in beta-thalassemia major patients in Southern Iran. Hemoglobin 2019;43(3):198-203. [DOI: 10.1080/03630269.2019.1651331] - DOI - PubMed
Sanjeeva 2015 {published data only}
    1. Sanjeeva GN, Nijaguna N, Matt M, Chebbi PG. Efficacy and safety of deferasirox when compared to deferiprone as oral iron chelating agent: a randomized control trial. Journal of Evolution of Medical and Dental Sciences 2015;4(24):4718-85.
Sebastian 2020 {published data only}
    1. Panachiyil GM, Babu T, Sebastian J, Ravi MD. Efficacy and tolerability of twice-daily dosing schedule of deferasirox in transfusion-dependent paediatric beta-thalassaemia patients: a randomized controlled study. Journal of Pharmacy Practice 2022;online:1-7. [CFGD REGISTER: TH220c] [DOI: 10.1177/08971900211038301] - DOI - PubMed
    1. Sebastian J, Babu T, Panachiyil GM, Ravi MD. Assessment of clinical outcome of twice daily dosing schedule of deferasirox in transfusion dependent paediatric beta thalassemia patients a randomized controlled study. Pharmacoepidemiology and Drug Safety 2020;29(Suppl 3):106. [CFGD REGISTER: TH220a]
    1. Sebastian J, Babu T, Panachiyil GM, Ravi MD. Efficacy, tolerability and medication adherence of twice-daily dosing schedule of deferasirox in transfusion-dependent paediatric beta thalassemia patients: a randomized controlled study. Value in Health Regional Issues 2020;22(S47):PIH17. [DOI: 10.1016/j.vhri.2020.07.244] - DOI
Shah 2021 {published data only}
    1. Shah S, Chaudhary Z, Rahman MU, Saadullah M, Aslam A, Abbas G, et al. Iron chelation therapy in beta-thalassemia major showing non-inferiority of oral chelator over parenteral chelator. Latin American Journal of Pharmacy 2021;40(4):655-62.
Shih 2020 {published data only}
    1. Shih S, Cohen LL. A systematic review of medication adherence interventions in pediatric sickle cell disease. Journal of Pediatric Psychology 2020;45(6):593-606. [DOI: 10.1093/jpepsy/jsaa031] - DOI - PubMed
Sidhu 2021 {published data only}
    1. Sidhu S, Kakkar S, Dewan P, Bansal N, Sobti PC. Adherence to iron chelation therapy and its determinants. International Journal of Hematology Oncology & Stem Cell Research 2021;15(1):27-34. - PMC - PubMed
Smith 2017 {published data only}
    1. Smith AW. Parent and adolescent factors related to adherence and health outcomes in sickle cell disease [PhD thesis]. Columbus, Ohio, USA: Electronic Theses & Dissertations Center, 2016.
Souran 2019 {published data only}
    1. Souran HM, Sanagouyemoharer GR, Shirazi M. Acceptance and commitment therapy improves psychological flexibility of students with thalassemia major: a randomized controlled trial. Journal of Practice in Clinical Psychology 2019;7(2):107-16.
Tripathy 2021 {published data only}
    1. Tripathy I, Panja A, Dolai TK, Mallick AK. Comparative efficacy and safety between deferiprone and deferasirox with special reference to serum ferritin level and cardiac function in Bengali beta-thalassemia major children. Hemoglobin (International Journal for Hemoglobin Research) 2021;45(5):296-302. [DOI: 10.1080/03630269.2021.1999258] - DOI - PubMed
UMIN 000007644 {published data only}
    1. UMIN000007644. A prospective study of treatment continuation rate with early low-dose iron chelation therapy for patients with transfusion-induced iron overload. center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009016 (first received 3 April 2012).
Vichinsky 2008 {published data only}
    1. Vichinsky E, Fischer R, Pakbaz Z, Onyekwere O, Porte, J, Swerdlow P, et al. Satisfaction and convenience of chelation therapy in patients with sickle cell disease (SCD): comparison between deferasirox (Exjade®, ICL670) and deferoxamine (DFO). Blood 2005;106(11 Pt 1):Abstract no. 2334. [DOI: ]
    1. Vichinsky E, Pakbaz Z, Onyekwere O, Porter J, Swerdlow P, Coates T, et al. Patient-reported outcomes of deferasirox (Exjade, ICL670) versus deferoxamine in sickle cell disease patients with transfusional hemosiderosis. Substudy of a randomized open-label phase II trial. Acta Haematologica 2008;119(3):133-41. [DOI: ] [PMID: ] - PubMed
Viola 2020 {published data only}
    1. Viola AS. The feasibility of a medical student mentoring program to improve transition of care among young adults with sickle cell disease [PhD thesis]. New Brunswick, New Jersey, USA: Rutgers University Community Repository, 2020.
Vlachodimitropoulou Koumoutsea 2017 {published data only}
    1. Vlachodimitropoulou Koumoutsea E. Novel approaches to iron chelation therapy: novel combinations and novel compounds [PhD thesis]. London, UK: University College London, 2017.
Waheed 2014 {published data only}
    1. Waheed N, Ali S, Butt MA. Comparison of deferiprone and deferrioxamine for the treatment of transfusional iron overload in children with beta thalassemia major. Journal of Ayub Medical College, Abbottabad: JAMC 2014;26(3):297-300. - PubMed
Walsh 2014 {published data only}
    1. Walsh KE, Cutrona SL, Kavanagh PL, Crosby LE, Malone C, Lobner K, et al. Medication adherence among pediatric patients with sickle cell disease: a systematic review. Pediatrics 2014;134(6):1175-83. - PMC - PubMed
Wilson 2017 {published data only}
    1. Wilson SM. Relationship between executive functioning and adherence in youth with sickle cell disease [PhD thesis]. Columbus, Ohio, USA: Electronic Theses & Dissertations Center, 2016.
Yarali 2006 {published data only}
    1. Yarali N, Fisgin T, Duru F, Kara A, Ecin N, Fitoz S, Erden I. Subcutaneous bolus injection of deferoxamine is an alternative method to subcutaneous continuous infusion. Journal of Pediatric Hematology/Oncology 2006;28(1):11-6. - PubMed

References to studies awaiting assessment

Bhojak 2020 {published data only}
    1. Bhojak R, Gohil J, Gosai M, Varghese B. Efficacy of once a month single dose intravenous (deferoxamine) versus daily oral (deferasirox) iron chelator in thalassemia major: an open label randomized parallel group active control interventional trial. International Journal of Scientific Research 2020;9(1):47-9. [DOI: 10.36106/ijsr] [URL: http://www.worldwidejournals.org/index.php/ijsr/article/view/1379] - DOI
    1. Bhojak RD, Gohil JR, Varghese B. Deferoxamine intravenous once a month injection single dose versus deferasirox oral daily: iron chelator in thalassemia major: an open label randomized parallel group active control interventional trial. Indian Journal of Hematology & Blood Transfusion 2020;36(1 Suppl):S65. [CFGD REGISTER: TH221]
    1. CTRI/2017/08/009441. A comparative trial to assess the efficacy of tablet deferasirox versus injection deferoxamine by reduction in serum ferritin level in pediatric thalassemia major patient in tertiary care hospital by prospective study [A study to compare effectiveness amongst two drugs,one is injection desferoxamine with tablet deferasirox as a chelator in thalassemia patients ]. ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19387&EncHid=&u... (first received 22 August 2017).
Crosby 2019 {published data only}
    1. Crosby LE, Kidwell KM, Hildenbrand AK, Quinn CT, McGrady ME. Feasibility of electronic monitoring of daily oral medications in adolescents with sickle cell disease. Blood 2019;134(Suppl 1):4701. [DOI: 10.1182/blood-2019-125875] - DOI
CTRI/2020/07/026771 {published data only}
    1. Efficacy of combination therapy with oral iron chelators in children with transfusion dependant beta-thalassemia major on assessing cardiac function by echocardiography and tissue doppler imaging- a hospital based open labelled randomised controlled trial [Effect of combination therapy with oral iron chelators on Heart function]. trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2020/07/026771 (first received 24 July 2020).
Eghbali 2019 {published data only}
    1. Eghbali A, Shokri P, Afzal RR, Bagheri B. A 1-year randomized trial of deferasirox alone versus deferasirox and deferoxamine combination for the treatment of iron overload in thalassemia major. Transfusion and Apheresis Science 2019;58(4):429-33. [CFGD REGISTER: TH208] - PubMed
    1. IRCT 20150119020715N4. The effect of Exjade and its combination therapy with Desferal is compared with the reduction of ferritin in patients with thalassemia major. www.en.irct.ir/trial/18313 (first received 17 December 2017) (retrospective).
EUCTR 2017‐003777‐34‐NL {published data only}EUCTR2017‐003777‐34‐NL
    1. 2017-003777-34. Clinical Trial Results: Proton pump inhibition for secondary hemochromatosis in hereditary anemia, a phase III placebo controlled randomized cross-over clinical trial. https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-003777-34/re... (first received 21 May 2022). - PMC - PubMed
    1. EUCTR2017-003777-34-NL. PPI in secondary hemochromatosis. trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2017-003777-34-NL (first received 22 February 2018).
EX‐PAT 2013 {published data only}
    1. Antmen B, Organ K, Sasmaz I, Berktas M, Kilinc Y. A cohort study to assess the contribution of patient compliance program on persistence to deferasirox in patients with chronic iron overload in Turkey (ex-pat program). Haematologica/the Hematology Journal 2013;98:713-4.
IRCT 2013 042213092N1 {published data only}IRCT2013042213092N1
    1. IRCT2013042213092N1. The effect of education base on empowering model on major thalassemia patients. en.irct.ir/trial/13021 (first received 3 February 2014).
IRCT 2016 0310026998N7 {published data only}
    1. IRCT 2016 0310026998N7. Comparison of the effect of deferasirox and deferiprone combination and defroxamine/deferiprone regimen among patients with beta-thalassemia. en.irct.ir/trial/22246 (first received 5 May 2018).
IRCT 2019 0106042262N1 {published data only}
    1. IRCT20190106042262N1. Compare the efficacy of combination deferasirox and deferiprone with deferoxamine and deferiprone in reducing heart and liver iron load in patients with transfusion-dpendent β-thalassemia. www.irct.ir/trial/36668 (first received 2 March 2019).
IRCT 2019 0827044634N1 {published data only}
    1. IRCT20190827044634N1. The effect of group hope therapy on hope and adherence to treatment in adolescents with β-thalassemia major. www.irct.ir/trial/41787 (first registered 1 November 2019).
IRCT 2020 0126046270N1 {published data only}
    1. IRCT20200126046270N1. The influence of education FRIENDS on anxiety and loneliness in children with major thalassemia (8-18 Years Old) in Golestan province in 2019. en.irct.ir/trial/45400 (first received 25 February 2020).
IRCT 2020 0606047670N2021 {published data only}
    1. IRCT20200606047670N2021. Investigating the effect of religious education in thalassemia [Investigating if the effect of religious care education on spiritual health and life expectancy in adolescents with thalassemia major]. en.irct.ir/trial/52675 (first received 8 January 2021).
NCT00004982 {published data only}
    1. NCT00004982. Combination iron chelation therapy. clinicaltrials.gov/ct2/show/NCT00004982 (first received 14 March 2000).

References to ongoing studies

CALYPSO {published data only}
    1. EUCTR 2013-004739-55-HU. Study to evaluate treatment compliance, efficacy and safety of an improved deferasirox formulation (granules) in pediatric patients (2-<18 years old) with iron overload. clinicaltrialsregister.eu/ctr-search/trial/2013-004739-55/HU (first received 25 July 2016).
    1. NCT02435212. Study to evaluate treatment compliance, efficacy and safety of an improved deferasirox formulation (granules) in pediatric patients (2-<18 years old) with iron overload. clinicaltrials.gov/ct2/show/NCT02435212 (first received 6 May 2015).
    1. Taher AT, Wali Y, Cruz MC, Charoenkwan P, Bachir J, Aushev A, et al. Compliance and clinical benefit of deferasirox granule formulation vs dispersible tablets in pediatric patients with transfusional iron overload: results from the phase II CALYPSO study. In: library.ehaweb.org/eha/2019/24th/266299/ali.t.taher.compliance.and.clini... European Hematology Association (EHA24); online conference; 2019 Jun 14. 2019. [ABSTRACT NO.: PF499]
IRCT 2015 101218603N2 {published data only}
    1. IRCT2015101218603N2. To assess compliance, efficacy and satisfaction with two different formulation of deferasirox in patients with transfusion-dependent beta-thalassemia. en.irct.ir/trial/16826 (first received 21 December 2015).
Madderom 2016 (TEAM study) {published data only}
    1. Madderom MJ, Heijdra J, Utens EM, Polinder S, Rijneveld AW, Cnossen MH. A randomized controlled trial studying the effectiveness of group medical appointments on self-efficacy and adherence in sickle cell disease (TEAM study): study protocol. BMC Hematology 2016;16(21):6. - PMC - PubMed
    1. NTR4750. A randomized trial evaluaTing the Effects of group medical AppointMents on self-efficacy and adherence in Sickle Cell Disease (TEAM study) [Effecten van GroepsconsulTen op zElfmAnageMent en therapietrouw in sikkelcelziekte (TEAM studie)]. trialsearch.who.int/Trial2.aspx?TrialID=NTR4750 (first received 13 August 2014).
NCT04877054 {published data only}
    1. NCT04877054. Pilot evaluation of a motivational interviewing intervention targeting adherence behaviors in youth with sickle cell disease. https://clinicaltrials.gov/ct2/show/NCT04877054 (first received 7 May 2021).

Additional references

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Aydinok 2014
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Deeks 2022
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EPOC 2015
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Fisher 2013
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Higgins 2017
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Higgins 2022
    1. Higgins JP, Eldridge S, Li T, editor(s) . Chapter 23: Including variants on randomized trials. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.3 (updated February 2022). Cochrane, 2022. Available from www.training.cochrane.org/handbook.
Lefebvre 2022
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