Anaemia
Conditions
Keywords
Iron, Anemia, Sodium Fe(III)-ethylenediaminetetraacetic acid (NaFeEDTA), Ferrous compounds, Child, preschool, Kenya
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).
Interventions
DIETARY_SUPPLEMENTLow-dose iron as NaFeEDTA
Daily home fortification for 30 days with 3 mg iron as NaFeEDTA, vitamin A (300 RE μg as retinyl palmitate) and 5 mg zinc (as gluconate)
DIETARY_SUPPLEMENTConventional dose iron as ferrous salt
Daily home fortification for 30 days with 12.5 mg iron as encapsulated ferrous fumarate, vitamin A (300 RE μg as retinyl palmitate) and 5 mg zinc (as gluconate)
DIETARY_SUPPLEMENTPlacebo
Daily home fortification for 30 days with vitamin A (300 RE μg as retinyl palmitate) and 5 mg zinc (as gluconate)
Sponsors
Maseno University
London School of Hygiene and Tropical Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Months to 36 Months
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Hemoglobin concentration | End of the 30-day fortification period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Iron status | End of the 30-day fortification period | Iron status will be assessed by plasma concentrations of ferritin and soluble transferrin receptor |
Other
| Measure | Time frame | Description |
|---|---|---|
| Haemoglobin concentration | Single measurement between 30 and 100 days after randomisation | At various time points in the post-intervention period, we will sample children without replacement to measure their haemoglobin concentration. Taking into account our wish to restrict phlebotomies during the post-intervention period to a single occasion per child, we will withdraw the child from further study. These measurements should allow us to estimate the time point when ≥10% of children has developed severe anaemia (haemoglobin concentration \<70 g/L). |
Countries
Kenya
Outcome results
None listed