Safe and Efficacious Iron for Children in Kenya

NCT ID: NCT02073149

Last Updated: 2015-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 338 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2014-12-31

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).

Conditions

Anaemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Low-dose iron as NaFeEDTA

Daily point-of-care fortification of (complementary) foods with 3 mg iron as NaFeEDTA.

Group Type: ACTIVE_COMPARATOR

Low-dose iron as NaFeEDTA

Intervention Type: DIETARY_SUPPLEMENT

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 point-of-care fortification of (complementary) foods with 12.5 mg iron as encapsulated ferrous fumarate.

Group Type: ACTIVE_COMPARATOR

Conventional dose iron as ferrous salt

Intervention Type: DIETARY_SUPPLEMENT

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 point-of-care fortification of (complementary) foods with placebo.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

Daily home fortification for 30 days with vitamin A (300 RE μg as retinyl palmitate) and 5 mg zinc (as gluconate)

Interventions

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)

Intervention Type: DIETARY_SUPPLEMENT

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)

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Daily home fortification for 30 days with vitamin A (300 RE μg as retinyl palmitate) and 5 mg zinc (as gluconate)

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

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).

• Minimum Eligible Age: 12 Months
• Maximum Eligible Age: 36 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Maseno University

OTHER

Sponsor Role: collaborator

London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hans Verhoef, PhD

Role: PRINCIPAL_INVESTIGATOR

London School of Hygiene and Tropical Medicine

Locations

Maseno University

Maseno, Nyanza Province, Kenya

Countries

Kenya

References

Teshome EM, Oriaro VS, Andango PEA, Prentice AM, Verhoef H. Adherence to home fortification with micronutrient powders in Kenyan pre-school children: self-reporting and sachet counts compared to an electronic monitoring device. BMC Public Health. 2018 Feb 1;18(1):205. doi: 10.1186/s12889-018-5097-2.

Reference Type: DERIVED

PMID: 29391008 (View on PubMed)

Teshome EM, Prentice AM, Demir AY, Andang'o PEA, Verhoef H. Diagnostic utility of zinc protoporphyrin to detect iron deficiency in Kenyan preschool children: a community-based survey. BMC Hematol. 2017 Jul 27;17:11. doi: 10.1186/s12878-017-0082-z. eCollection 2017.

Reference Type: DERIVED

PMID: 28770094 (View on PubMed)

Teshome EM, Andang'o PEA, Osoti V, Terwel SR, Otieno W, Demir AY, Prentice AM, Verhoef H. Daily home fortification with iron as ferrous fumarate versus NaFeEDTA: a randomised, placebo-controlled, non-inferiority trial in Kenyan children. BMC Med. 2017 Apr 28;15(1):89. doi: 10.1186/s12916-017-0839-z.

Reference Type: DERIVED

PMID: 28449690 (View on PubMed)

Other Identifiers

LSHTM-2542

Identifier Type: -

Identifier Source: org_study_id