Protocol for a randomised, multicentre, four-arm, double-blinded, placebo-controlled trial to assess the benefits and safety of iron supplementation with malaria chemoprevention to children in Malawi: IRMA trial

Martin N Mwangi; Glory Mzembe; Chikondi C Ngwira; Maclean Vokhiwa; Mayamiko D Kapulula; Leila M Larson; Sabine Braat; Rebecca Harding; Alistair R D McLean; Jena D Hamadani; Beverley-Ann Biggs; Ricardo Ataíde; Kamija S Phiri; Sant-Rayn Pasricha

doi:10.1136/bmjopen-2022-069011

Protocol for a randomised, multicentre, four-arm, double-blinded, placebo-controlled trial to assess the benefits and safety of iron supplementation with malaria chemoprevention to children in Malawi: IRMA trial

BMJ Open. 2023 Oct 13;13(10):e069011. doi: 10.1136/bmjopen-2022-069011.

Authors

Martin N Mwangi^{1

2}, Glory Mzembe^{3

4}, Chikondi C Ngwira³, Maclean Vokhiwa^{3

4}, Mayamiko D Kapulula³, Leila M Larson⁵, Sabine Braat^{6

7

8}, Rebecca Harding⁸, Alistair R D McLean^{7

8}, Jena D Hamadani⁹, Beverley-Ann Biggs^{6

10}, Ricardo Ataíde^{6

8}, Kamija S Phiri^{3

4}, Sant-Rayn Pasricha^{8

10

11}

Affiliations

¹ Training and Research Unit of Excellence (TRUE), Blantyre, Malawi mmwangi@true.mw.
² The Micronutrient Forum, Healthy Mothers Healthy Babies Consortium, Washington DC, Washington, USA.
³ Training and Research Unit of Excellence (TRUE), Blantyre, Malawi.
⁴ Department of Public Health, Kamuzu University of Health Sciences, Blantyre, Malawi.
⁵ Department of Health Promotion, Education, and Behaviour, University of South Carolina Arnold School of Public Health, Columbia, South Carolina, USA.
⁶ Department of Infectious Diseases at the Peter Doherty Institute of Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia.
⁷ Centre for Epidemiology and Biostatistics, University of Melbourne School of Population and Global Health, Carlton, Victoria, Australia.
⁸ Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
⁹ International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
¹⁰ Diagnostic Haematology, The Royal Melbourne Hospital; and Clinical Haematology, Melbourne, Victoria, Australia.
¹¹ Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia.

Abstract

Introduction: Approximately 40% of children aged 6-59 months worldwide are anaemic. Iron-containing multiple micronutrient powders (MNPs) and iron supplements (syrup/drops) are used to combat anaemia in children in different parts of the world. However, evidence for functional benefits of iron supplementation in children is scarce, and potential risks remain poorly defined, particularly concerning diarrhoea and malaria. This trial aims to determine if: (1) the efficacy of iron supplements or MNPs (containing iron) given with malaria chemoprevention is superior to malaria chemoprevention alone, or (2) if the efficacy of malaria chemoprevention alone is superior to placebo on child cognitive development.

Methods and analysis: IRMA is a four-arm, parallel-group, double-blinded, placebo-controlled, triple-dummy, randomised trial in Southern Malawi. The study recruits 2168 infants aged 6 months, with an intervention period of 6 months and a post-intervention period of a further 6 months. Children are randomised into four arms: (1) No intervention (placebo); (2) malaria chemoprevention only; (3) MNPs and malaria chemoprevention; and (4) iron syrup and malaria chemoprevention. The primary outcome, cognitive development (Cognitive Composite Score (CogCS)), is measured at the end of the 6 months intervention. Secondary outcomes include CogCS at a further 6 months post-intervention, motor, language and behavioural development, physical growth and prevalence of anaemia and iron deficiency. Safety outcomes include incidence of malaria and other infections, and prevalence of malaria parasitaemia during and post-intervention period.

Ethics and dissemination: The trial is approved by the National Health Sciences Research Committee (#19/01/2213) (Malawi) and the Human Research Ethics Committee (WEHI: 19/012) (Australia). Written informed consent in the local language is obtained from each participant before conducting any study-related procedure. Results will be shared with the local community and internationally with academic and policy stakeholders.

Trial registration number: ACTRN12620000386932.

Keywords: Anaemia; Infection control; Nutrition; PUBLIC HEALTH.

Publication types

Clinical Trial Protocol
Research Support, Non-U.S. Gov't

MeSH terms

Anemia* / drug therapy
Chemoprevention
Child
Dietary Supplements
Humans
Infant
Iron / therapeutic use
Malaria* / drug therapy
Malaria* / prevention & control
Malawi / epidemiology
Multicenter Studies as Topic
Randomized Controlled Trials as Topic

Substances

Iron