Ferric carboxymaltose with or without phosphate substitution in iron deficiency or iron deficiency anemia before elective surgery - The DeFICIT trial
- PMID: 39671753
- DOI: 10.1016/j.jclinane.2024.111727
Ferric carboxymaltose with or without phosphate substitution in iron deficiency or iron deficiency anemia before elective surgery - The DeFICIT trial
Abstract
Background: Iron deficiency anemia in the perioperative setting is treated predominantly with intravenous iron formulation, of which ferric carboxymaltose may induce hypophosphatemia by modulating fibroblast growth factor 23.
Methods: In this single-center, prospective, randomized, double-blind trial, we consented 92 adult patients scheduled for elective major abdominal or thoracic surgery. These patients either had isolated iron deficiency (plasma ferritin <100 ng/mL or transferrin saturation < 20 %) or iron deficiency anemia (hemoglobin (Hb) 100-130 g/L with plasma ferritin <100 ng/mL or transferrin saturation < 20 %). Preoperatively, participants received a single preoperative intravenous dose of ferric carboxymaltose and were then randomly assigned to receive either phosphate or placebo, administered orally three times a day for 30 days corresponding to an 18 mmol dose of daily phosphate supplementation in the intervention group. The primary endpoint was the minimum serum phosphate concentration during follow-up visits. The key secondary efficacy endpoint was mean perioperative hemoglobin concentration of postoperative days 0, 2 and 4, assessing the non-inferiority of additional phosphate supplementation.
Results: We randomly consented 46 patients in each group (mean ± SD age 56 ± 17 years, 57 % female). Minimal phosphate concentration was 0.49 ± 0.21 mmol/L in the treatment group and 0.42 ± 0.17 mmol/L in the placebo group (p = 0.12, two-sided p-value). Average mean hemoglobin was 110 ± 16 g/L in the treatment and 113 ± 13 g/L in the placebo group (p = 0.023, one-sided p-value for non-inferiority). Hypophosphatemia occurred in 32 patients (70 %) of the treatment group and in 39 patients (85 %) of the placebo group (odds ratio 0.15, 95 % CI from 0.02 to 0.77, p = 0.014). Secondary outcomes, such as rescue medication use, core muscle strength and MOCA test scores, did not differ between groups.
Conclusion: Co-administration of oral phosphate supplementation to ferric carboxymaltose cannot prevent hypophosphatemia. However, hypophosphatemia occurs in fewer patients. Phosphate co-administration did not impede the treatment of iron deficiency anemia with ferric carboxymaltose.
Keywords: Anemia; Ferric carboxymaltose; Hypophosphatemia; Iron deficiency; Phosphate substitution.
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Donat R. Spahn reports financial support was provided by CSL Vifor. Donat R. Spahn reports financial support was provided by Swiss Foundation for Anesthesia Research. Alexander Kaserer received lecture honoraria from Bayer AG (Switzerland), CSL Behring GmbH (Switzerland) and advisory honoraria from AstraZeneca AG (Switzerland) and Pharmacosmos (Switzerland). Julia Braun, Alexander Mair, Andreas Hülsmeier, Gergely Karsai, Julian Rössler, Samira Akbas, Greta Gasciauskaite, Heike A. Bischoff-Ferrari, Pierre-Alain Clavien and Matthias Turina have no conflicts of interest to declare. Dr. Gabriela H. Spahn received honoraria for lectures from CSL Vifor (Switzerland) Villars-sur-Glâne, Switzerland. Martin Schläpfer has no conflicts of interest related to this study but has obtained unrestricted research grants from Roche Diagnostics International (Rotkreuz, Switzerland) and Sedana Medical (Danderyd, Sweden) and has submitted one patent for mitigating the negative effects of surgery and anesthesia with O2/ CO2 mixtures and one for an injectable formula to attenuate the harmful effects of sepsis. Isabelle Opitz has no real conflicts of interest. The following could be perceived as such: Roche (Institutional Grant and Speakers Bureau), AstraZeneca (Advisory Board and Speakers Bureau), MSD (Advisory Board), BMS (Advisory Board), Medtronic (Institutional Grant and Advisory Board), Intuitive (Proctorship). Donat R. Spahn: Dr. Spahn's former academic department is receiving grant support from the Swiss National Science Foundation, Berne, Switzerland, the Swiss Society of Anesthesiology and Perioperative Medicine (SSAPM), Berne, Switzerland, the Swiss Foundation for Anesthesia Research, Zurich, Switzerland, and CSL Vifor (International) AG, St. Gallen, Switzerland. Donat R. Spahn is co-chair of the ABC-Trauma Faculty, sponsored by unrestricted educational grants from Alexion Pharma Germany GmbH, Munich, Germany, CSL Behring GmbH, Marburg, Germany, and LFB Biomédicaments, Courtaboeuf Cedex, France. Donat R. Spahn received honoraria / travel support for consulting or lecturing from: Alliance Rouge, Bern, Switzerland, Danube University of Krems, Austria, European Society of Anesthesiology and Intensive Care, Brussels, BE, International Foundation for Patient Blood Management, Basel, Switzerland, Korean Society of Anesthesiologists, Seoul, Korea, Network for the Advancement of Patient Blood Management, Haemostasis and Thrombosis, Paris, France, Society for the Advancement of Blood Management, Mount Royal NJ, Alexion Pharmaceuticals Inc., Boston, MA, AstraZeneca AG, Baar, Switzerland, Bayer AG, Zürich, Switzerland, B. Braun Melsungen AG, Melsungen, Germany, Baxter AG, Glattpark, Switzerland, CSL Behring GmbH, Hattersheim am Main, Germany and Berne, Switzerland, CSL Vifor (Switzerland) Villars-sur-Glâne, Switzerland, CSL Vifor (International), St. Gallen, Switzerland, Celgene International II Sàrl, Couvet, Switzerland, Daiichi Sankyo AG, Thalwil, Switzerland, Haemonetics, Braintree, MA, USA, iSEP, Nantes, France, LFB Biomédicaments, Courtaboeuf Cedex, France, Merck Sharp & Dohme, Kenilworth, New Jersey, USA, Novo Nordisk Health Care AG, Zurich, Switzerland, Octapharma AG, Lachen, Switzerland, Pharmacosmos A/S, Holbaek, Denmark, Pierre Fabre Pharma, Alschwil, Switzerland, Portola Schweiz GmbH, Aarau, Switzerland, Roche Diagnostics International Ltd., Reinach, Switzerland, Sarstedt AG & Co., Sevelen, Switzerland and Nümbrecht, Germany, Shire Switzerland GmbH, Zug, Switzerland, Takeda, Glattpark, Switzerland, Werfen, Bedford, MA, Zuellig Pharma Holdings, Singapore, Singapore. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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