Safe and Efficacious Iron for Children in Kenya

Phase 2

Completed

• Conditions: Anaemia
• Interventions: Dietary Supplement: Low-dose iron as NaFeEDTA; Dietary Supplement: Placebo; Dietary Supplement: Conventional dose iron as ferrous salt

• Registration Number: NCT02073149
• Lead Sponsor: London School of Hygiene and Tropical Medicine

Brief Summary

This study will determine whether the haemoglobin response to daily home fortification for 30 days with 3mg iron as NaFeEDTA is non-inferior to 12.5 mg iron as encapsulated ferrous fumarate.

Detailed Description

Background: Fortification of local complementary foods and supplementation with micronutrient powders including iron has been shown to prevent anaemia. Iron can cause complaints (diarrhoea, constipation, etc.) related to oxidative stress in the intestine, however, and at doses conventionally used for daily supplementation, iron can increase rates of malaria and diarrhoea. A lower dose of iron (3mg/day) as NaFEEDTA can reduce these adverse effects whilst having similar or superior efficacy in improving iron status as conventional-dose iron (12.5mg) as ferrous salts.

Objective: The primary aim is to compare daily home fortification with 3mg iron as NaFeEDTA versus 12.5 mg iron as encapsulated ferrous fumarate regarding haemoglobin concentration at the end of the 30-day fortification period.

Methods: Rural children aged 12-36 months (n=324) will receive albendazole and praziquantel against helminth infections, and preventive chemotherapy against malaria with dihydroartemisinin-piperaquine. They will subsequently be randomised to daily home fortification for 30 days with sachets containing either a) 3 mg iron as NaFeEDTA; b) 12.5 mg iron as encapsulated ferrous fumarate; or c) placebo. Parents or guardians will be instructed to mix the contents of the sachets with solid or semi-solid, ready-prepared foods. Adherence will be assessed by an electronic monitoring and time-recording device in the cap of a dispensing bottle containing the sachets. At the end of the 30-day fortification period, a venous blood sample will be collected to measure indicators of iron status and inflammation. Children who received iron will continue to be followed for a maximum of 120 days after randomisation to estimate the time point when ≥10% of children has developed severe anaemia (haemoglobin concentration \<70 g/L).

Study Timeline

• Status Verified: 2014-02
• Study First Submitted: 2014-02-25
• Study First Submitted QC: 2014-02-25
• Study First Posted: 2014-02-27
• Study Start: 2014-06
• Primary Completion: 2014-12
• Study Completion: 2014-12
• Last Update Submitted: 2015-04-09
• Last Update Posted: 2015-04-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 338

Inclusion Criteria

1. Aged 12-36 months;
2. Residing in the study area;
3. Planning to be in the area for the duration of the intervention and follow-up;
4. Study protocol accepted and informed consent given by at least one parent or guardian

Exclusion Criteria

1. Known or reported allergy to dihydroartemisinin, piperaquine, benzimidazole drugs or praziquantel;
2. A sibling from the same household already randomised to intervention;
3. Severely malnourished (weight-for-height z-score < -3 SD) (for ethical reasons);
4. Presence of fever (axillary temperature ≥ 37.5 ºC) (to avoid inflammation-induced effects on iron status markers);
5. Presence of reported or suspected systemic disorder (e.g. HIV infection, sickle cell disease) (to avoid inflammation-induced effects on iron status markers and to avoid attrition);
6. Missed one or several doses of the 3-day course of dihydroartemisinin-piperaquine (to ensure that participants are protected against malaria for the duration of the iron intervention);
7. No blood sample collected, or blood volume collected < 5 mL;
8. Haemoglobin concentration < 70 g/L (to prevent severe anaemia).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low-dose iron as NaFeEDTA	Low-dose iron as NaFeEDTA	Daily point-of-care fortification of (complementary) foods with 3 mg iron as NaFeEDTA.
Placebo	Placebo	Daily point-of-care fortification of (complementary) foods with placebo.
Conventional dose iron as ferrous salt	Conventional dose iron as ferrous salt	Daily point-of-care fortification of (complementary) foods with 12.5 mg iron as encapsulated ferrous fumarate.

Primary Outcome Measures

Name	Time	Method
Hemoglobin concentration	End of the 30-day fortification period

Secondary Outcome Measures

Name	Time	Method
Iron status	End of the 30-day fortification period	Iron status will be assessed by plasma concentrations of ferritin and soluble transferrin receptor
Serum concentration of non-transferrin bound iron	3 hours after ingesting the first fortificant dose
Faecal calprotectin concentration	End of the 30-day fortification period	Faecal calprotectin concentration is used as an indicator of intestinal inflammation
P. falciparum infection	End of the 30-day fortification period	P. falciparum infection will be defined as the presence of either asexual parasites in blood smears or parasite antigens (either histidine-rich protein-2, or Plasmodium lactate dehydrogenase) in whole blood
Adherence to intervention	End of the 30-day fortification period	Adherence will be defined for each individual as the number of days that the dispensing bottle has been opened during the 30-day intervention period

Trial Locations

Locations (1)

Maseno University; 🇰🇪 Maseno, Nyanza Province, Kenya