Safe and Efficacious Iron for Children in Kenya

Anaemia Clinical Trial

— SEICK  

Official title:

Comparison of Home Fortification With Two Iron Formulations in Kenyan Children Protected Against Malaria by Artemisinin-based Combination Therapy: a Placebo-controlled Non-inferiority Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02073149
• Other study ID #: LSHTM-2542
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: February 25, 2014
• Last updated: April 9, 2015
• Start date: June 2014
• Est. completion date: December 2014

Study information

• Verified date: February 2014
• Source: London School of Hygiene and Tropical Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: Kenya: Ethical Review Committee
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 338
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 12 Months to 36 Months

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Anaemia

Intervention

Dietary Supplement:
• Low-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)
• Conventional 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)
• Placebo
Daily home fortification for 30 days with vitamin A (300 RE µg as retinyl palmitate) and 5 mg zinc (as gluconate)

Locations

Country	Name	City	State
Kenya	Maseno University	Maseno	Nyanza Province

Sponsors (2)

Lead Sponsor	Collaborator
London School of Hygiene and Tropical Medicine	Maseno University, Maseno, Kenya

Country where clinical trial is conducted

Kenya, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Haemoglobin concentration	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).	Single measurement between 30 and 100 days after randomisation	No
Primary	Hemoglobin concentration		End of the 30-day fortification period	No
Secondary	Iron status	Iron status will be assessed by plasma concentrations of ferritin and soluble transferrin receptor	End of the 30-day fortification period	No
Secondary	Serum concentration of non-transferrin bound iron		3 hours after ingesting the first fortificant dose	Yes
Secondary	Faecal calprotectin concentration	Faecal calprotectin concentration is used as an indicator of intestinal inflammation	End of the 30-day fortification period	Yes
Secondary	P. falciparum infection	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	End of the 30-day fortification period	Yes
Secondary	Adherence to intervention	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	End of the 30-day fortification period	No