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Randomized Controlled Trial
. 2018 Sep 21;18(1):476.
doi: 10.1186/s12879-018-3379-z.

Methods for conducting a double-blind randomized controlled clinical trial of three days versus five days of amoxicillin dispersible tablets for chest indrawing childhood pneumonia among children two to 59 months of age in Lilongwe, Malawi: a study protocol

Amy Sarah Ginsburg  1 , Susanne J May  2 , Evangelyn Nkwopara  3 , Gwen Ambler  4 , Eric D McCollum  5 , Tisungane Mvalo  6 , Ajib Phiri  7 , Norman Lufesi  8 , Salim Sadruddin  9
Affiliations
Randomized Controlled Trial

Methods for conducting a double-blind randomized controlled clinical trial of three days versus five days of amoxicillin dispersible tablets for chest indrawing childhood pneumonia among children two to 59 months of age in Lilongwe, Malawi: a study protocol

Amy Sarah Ginsburg et al. BMC Infect Dis. .

Abstract

Background: Pneumonia is the leading infectious cause of death in children under 5 years of age around the globe. In addition to preventing pneumonia, there is a critical need to provide greater access to appropriate and effective treatment. Studies in Asia have evaluated the effectiveness of 3 days of oral amoxicillin for the treatment of fast-breathing pneumonia; however, further evidence is needed to determine if 3 days of oral amoxicillin is also effective for the treatment of chest indrawing pneumonia.

Methods: This is a double-blind, randomized, non-inferiority trial with the objective to assess the effectiveness of shorter duration amoxicillin dispersible tablet (DT) treatment of chest indrawing childhood pneumonia in a malaria-endemic region of Malawi. The primary objective of this study is to determine whether 3 days of treatment with oral amoxicillin DT in HIV-uninfected Malawian children two to 59 months of age with chest indrawing pneumonia is as effective as 5 days of treatment. The study will enroll 2000 children presenting to Kamuzu Central or Bwaila District Hospitals in Lilongwe, Malawi. Each child will be randomized to either 3 days of amoxicillin DT followed by 2 days of placebo DT or 5 days of amoxicillin DT. Children in the study will be hospitalized for 48 h after enrollment and will have scheduled study visits at Days 2, 4, 6 and 14. Treatment failure by Day 6 is the primary outcome. We hypothesize that the rates of treatment failure will be similar in both arms and that 3 days of treatment will be non-inferior to 5 days of amoxicillin DT for chest indrawing pneumonia using a relative non-inferiority margin of 1.5. This trial was approved by the Western Institutional Review Board and Malawi College of Medicine Research and Ethics Committee.

Discussion: Given the paucity of data from Africa, African-based research is necessary to establish appropriate duration of treatment with amoxicillin DT for chest indrawing childhood pneumonia in malaria-endemic settings in the region. An expanded evidence base will contribute to future iterations of World Health Organization Integrated Management of Childhood Illness guidelines.

Trial registration: NCT02678195 : Pre-results. Date registered February 9, 2016.

Keywords: Africa; Amoxicillin; Chest indrawing; Childhood pneumonia; Treatment failure.

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Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the Western Institutional Review Board in the state of Washington, USA; the Malawi College of Medicine Research and Ethics Committee, Blantyre, Malawi; and the Malawi Pharmacy, Medicines and Poisons Board. Written informed consent is obtained by trained study staff from all eligible children’s caregivers prior to enrollment.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Map of study area in Lilongwe, Malawi
Fig. 2
Fig. 2
Schedule of enrollment, intervention, and assessment
Fig. 3
Fig. 3
Framework to ensure child safety in the study
See this image and copyright information in PMC

References

    1. Liu L, Oza S, Hogan D, Perin J, Rudan I, Lawn JE, et al. Global, regional, and national causes of child mortality in 2000–13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet. 2015;385(9966):430–440. doi: 10.1016/S0140-6736(14)61698-6. - DOI - PubMed
    1. Pakistan Multicentre Amoxycillin Short Course Therapy pneumonia study g Clinical efficacy of 3 days versus 5 days of oral amoxicillin for treatment of childhood pneumonia: a multicentre double-blind trial. Lancet. 2002;360(9336):835–841. doi: 10.1016/S0140-6736(02)09994-4. - DOI - PubMed
    1. Agarwal G, Awasthi S, Kabra SK, Kaul A, Singhi S, Walter SD, et al. Three day versus five day treatment with amoxicillin for non-severe pneumonia in young children: a multicentre randomised controlled trial. BMJ. 2004;328(7443):791. doi: 10.1136/bmj.38049.490255.DE. - DOI - PMC - PubMed
    1. Hazir T, Nisar YB, Abbasi S, Ashraf YP, Khurshid J, Tariq P, et al. Comparison of oral amoxicillin with placebo for the treatment of world health organization-defined nonsevere pneumonia in children aged 2-59 months: a multicenter, double-blind, randomized, placebo-controlled trial in Pakistan. Clin Infect Dis. 2011;52(3):293–300. doi: 10.1093/cid/ciq142. - DOI - PubMed
    1. WHO . Revised WHO classification and treatment of pneumonia in children at health facilities: evidence summaries. Geneva: World Health Organization; 2014. - PubMed

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