Clinical trial NCT02073149: Safe and Efficacious Iron for Children in Kenya
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Anaemia
Keywords: Iron
Anemia
Sodium Fe(III)-ethylenediaminetetraacetic acid (NaFeEDTA)
Ferrous compounds
Child, preschool
Kenya
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: Maseno University
First posted: 2014-02-27
Enrollment: 338
Sex: ALL
Minimum age (years): 12
Maximum age (years): 36
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

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).

Primary outcomes:
measure: Hemoglobin concentration
timeFrame: End of the 30-day fortification period
Secondary outcomes:
measure: Iron status
timeFrame: End of the 30-day fortification period
measure: Serum concentration of non-transferrin bound iron
timeFrame: 3 hours after ingesting the first fortificant dose
measure: Faecal calprotectin concentration
timeFrame: End of the 30-day fortification period
measure: P. falciparum infection
timeFrame: End of the 30-day fortification period
measure: Adherence to intervention
timeFrame: End of the 30-day fortification period
Other outcomes:
measure: Haemoglobin concentration
timeFrame: Single measurement between 30 and 100 days after randomisation
Locations:
city: Maseno
country: Kenya
facility: Maseno University
state: Nyanza Province
Study officials:
affiliation: London School of Hygiene and Tropical Medicine
name: Hans Verhoef, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.