Benefits and safety of IRon supplementation with MAlaria chemoprevention to children in Malawi (IRMA) - A randomised controlled trial
College of Medicine, University of Malawi
2,168 participants
Apr 13, 2020
Interventional
Conditions
Summary
Hypothesis: Cognitive development at the end of intervention in children receiving iron syrup plus DP, or iron-containing MNPs plus DP, is superior to that of children receiving DP alone, or DP alone is superior to placebo. The primary objective for this study is to deterimine if iron supplements or iron-containing MNPs given under DP cover is superior to DP alone or DP alone is superior to placebo on child cognitive development at the end of intervention. Methods: This will be a four-arm parallel-group, double blinded, placebo controlled, triple dummy, individually randomised trial. The study will compare the effects of: a) no intervention, b) DP alone, c) MNP+DP, and d) iron supplements +DP after both 6-months intervention and 6 months follow-up post-intervention to evaluate both immediate and medium-term effects. 2168 six months (+/- 14 days) old children (542 in each arm) will be recruited. Eligible children will include those with Hb>=7.0g/dL while those with gross developmental delay, congenital anomalies and severe infective illness will be excluded. Expected findings: In this study, we will measure childs’s cognitive, motor and language development after iron supplementation and DP cover as measured on Bayley-III, child’s behaviour measured on Wolke’s rating scales, temperament, quality of home stimulation using family care indicators. The safety of iron supplements and MNPs will be measured though morbidity assessment.
Eligibility
Inclusion Criteria2
- Infants aged 6 months (+/- 14 days) at the time of randomisation
- Has a legally acceptable guardian/representative capable of understanding the informed consent document and providing consent on the participant’s behalf
Exclusion Criteria9
- Severe anaemia (Hb<7g/dL) or
- Current infective illness with fever (respiratory infection, diarrhoea, malaria); however, children will be screened again after recovery and recruited as long as they meet the age eligibility criteria at second screening
- Severe malnutrition (weight-for-length z-score<-3);
- Established diagnosis of haemoglobinopathy (e.g. sickle cell disease, beta thalassaemia major, HbE-beta thalassaemia).
- Legal guardian unwilling or unable to provide written informed consent
- Known congenital anomaly, developmental disorder or severe developmental delay
- Children with physical or behavioural problems that will make it impossible to test the child
- Children of multiple birth e.g. twin, triplets etc.
- Currently consuming MNPs e.g. from the National MNP programme
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Interventions
Combinations of three drugs will be administered to participants: 1. DP 20mg dihydroartemisinin/ 160mg piperaquine tablets) orally, three consecutive days every 4 weeks for 6 months DP will be dosed by weight according to WHO recommendations: <8kg 1 tablet/d for 3d; 8-<11kg 1.5 tablets/d for 3d; 11-<17kg 2 tablets/d for 3d 2. Multiple Micronutrient Powders: sprinkled over food or dissolved in breastmilk Composition per one gram sachet: • Iron 10 mg (as coated Ferrous fumerate, NaFe EDTA*or Ferrous bisglycinate) • Zinc 4.1. mg (as Zinc sulphate, or gluconate) • Vitamin A 400 µg (as dry CWS vitamin A acetate or palmitate beadlets) Vitamin C 30 mg (as sodium or calcium ascorbate) • Vitamin D 5 µg (200IU) (as dry CWS Cholecalciferol) • Vitamin E 5 mg TE (as CWS d or dl-alpha tocopheryl acetate) • Vitamin B1 0.5 mg (as Thiamine mononitrate) • Vitamin B2 0.5. mg (Riboflavin or riboflavin -5-phosphate) • Vitamin B3 6 mg (as Nicotinamide) • Vitamin B6 0.5. mg (as Pyridoxine hydrochloride) • Vitamin B12 0.9 µg (1% or 0.1% Cyanocobalamin on a carrier ) • Folic acid 90 µg (anhydrous) • Copper 0.56 mg (as Copper gluconate or sulphate) • Selenium 17 µg (as Sodium selenate or selenite or selenomethionine) • Iodine 90 µg (as Potassium iodide, or potassium iodate) • Maltodextrin as vehicle for micronutrients 3. Iron syrup: Elemental Iron 10mg as ferrous sulfate, provided as 1.3mL of of 8mg/mL solution. There will be four groups in this trial: 1) Placebo DP plus placebo MNPs plus placebo iron syrup (No intervention): Placebo MNPs (maltodextrin vehicle only) daily for 6 months plus placebo DP (tablets) three consecutive days every 4 weeks for 6 months plus placebo iron syrup daily. 2) Active DP plus placebo MNPs plus placebo iron syrup (DP alone): Active DP (20mg dihydroartemisinin/ 180mg piperaquine tablets) dosed by body weight, three consecutive days every 4 weeks plus daily placebo MNPs (maltodextrin) daily, plus daily placebo iron syrup, for 6 months 3) Active DP plus active MNPs plus placebo iron syrup (DP+MNP): Active DP as above, plus daily active MNPs containing 10.0mg iron and other micronutrients (see below), plus placebo iron syrup daily for 6 months 4) Active DP plus placebo MNPs plus active iron syrup (DP+iron syrup): Active DP as above, plus placebo MNPs as above, plus active iron syrup containing 10.0mg ferrous sulfate daily. Adherence will be monitored by direct questioning of parents/ guardians at fortnightly home visits. Based on the National Health Sciences Research Committee's guidance, a pandemic rationalisation plan was developed in 2020 to preemptively minimise any impacts of the pandemic on the health of the participants and staff involved in the trial. Once the pandemic rationalisation plan was active, the fortnightly monitoring home visits of parents/guardians were reduced to a monthly visit instead. The pandemic rationalisation plan received ethics approval in Malawi and Australia.
Locations(1)
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ACTRN12620000386932