Clinical trial NCT01210040: Long-term Iron Supplements and Malaria Risk in Early Pregnancy: a Randomized Controlled Trial
Official title: Malaria Risk Prior to and During Early Pregnancy in Nulliparous Women Receiving Long-term Weekly Iron and Folic Acid Supplementation (WIFS): a Non-inferiority Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Malaria
Keywords: Pregnancy
Iron deficiency
Iron supplementation
Burkina Faso
Lead sponsor: Liverpool School of Tropical Medicine
Sponsor class: OTHER
Collaborators: name: Institute of Tropical Medicine, Belgium
name: University of Manchester
name: Institut de Recherche en Sciences de la Sante-Direction Regionale de l'Ouest
name: Centre Muraz
name: National Institutes of Health (NIH)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2010-09-28
Enrollment: 1959
Sex: FEMALE
Minimum age (years): 15
Maximum age (years): 24
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: A randomized double-blind controlled trial will be carried out in which young, nulliparous (having never given birth) women will be randomly assigned to receive weekly supplementation with either iron and folic acid or folic acid alone. Women will be followed-up weekly up to 18 months. Women who become pregnant will be followed-up until delivery. Malaria risk in both groups will be compared by assessing the prevalence of peripheral parasitaemia at the first antenatal clinic visit for pregnant women and at the end of the first malaria transmission season for non-pregnant women. The incidence of clinical malaria will be assessed by active and passive case detection throughout the follow-up period.


Eligibility criteria: Inclusion Criteria:

* Female
* At least 15 and less than 25 years old at enrolment
* Never given birth
* Resident within the Demographic Surveillance System (DSS) area
* Willing to adhere to the study requirements (including weekly observed drug intake)
* Provision of written informed consent (if non emancipated minor by guardian/parent with minor's assent

Exclusion Criteria:

* No menses for \>3 months and/or palpable uterus or positive pregnancy test if history unclear
* Concurrent enrolment in another study
* Intention to move out of the study area for more than 2 months within the next 18 months
* Any significant illness at the time of screening that requires hospitalization, including clinical signs of severe anaemia (conjunctival or mucosal pallor, tachycardia, respiratory distress)
* History or presence of major clinical disease likely to influence pregnancy outcome (sickle cell disease, diabetes mellitus, severe renal or heart disease, open tuberculosis, epilepsy)

Primary outcomes:
measure: Prevalence of peripheral parasitaemia at first antenatal clinic visit (13-16 weeks gestation)
timeFrame: Nov 2013
Secondary outcomes:
measure: a) In the pregnant cohort: Prevalence of iron deficiency at first antenatal visit
timeFrame: Sept 2013
measure: a) In the pregnant cohort: Prevalence of anaemia at first antenatal clinic visit
timeFrame: Sept 2013
measure: a) In the pregnant cohort: Incidence of clinical malaria during the first and subsequent trimesters
timeFrame: Jan 2014
measure: a) In the pregnant cohort: Incidence of adverse pregnancy outcomes
timeFrame: Jan 2014
measure: a) In the pregnant cohort: Mean birth weight and prevalence of low birth weight (<2500g)
timeFrame: Jan 2014
measure: a) In the pregnant cohort: Mean gestational age at delivery
timeFrame: Jan 2014
measure: a) In the pregnant cohort: Prevalence of placental malaria
timeFrame: Jan 2014
measure: a) In the non-pregnant cohort: Prevalence of peripheral parasitaemia during the first rainy season after at least six months of supplementation
timeFrame: Nov 2012
measure: a) In the non-pregnant cohort: Incidence of clinical malaria
timeFrame: Nov 2013
measure: a) In the non-pregnant cohort: Incidence of gastrointestinal adverse events
timeFrame: Nov 2013
measure: a) In the non-pregnant cohort: Prevalence of iron deficiency after at least 18 months supplementation
timeFrame: Nov 2013
measure: a) In the non-pregnant cohort: Prevalence of anaemia after at least 18 months supplementation
timeFrame: Nov 2013
measure: a) In the non-pregnant cohort: Adherence to supplementation
timeFrame: Nov 2013
measure: a) In the non-pregnant cohort: Acceptability of weekly supplementation
timeFrame: June 2013
measure: In the non-pregnant cohort: Prevalence of bacterial vaginosis at end assessment
timeFrame: Nov 2013
measure: a) In the non-pregnant cohort: Prevalence of bacterial vaginosis at end assessment
timeFrame: Nov 2013
measure: a) In the non-pregnant cohort: Prevalence of bacterial vaginosis at first antenatal visit
timeFrame: Nov 2013
measure: a) In the non-pregnant cohort: Prevalence of iron deficiency at key study visits
timeFrame: Nov 2013
measure: a) In the non-pregnant cohort: Prevalence of peripheral parasitaemia at end assessment
timeFrame: Nov 2013
Other outcomes:
Locations:
city: Bobo-Dioulasso 01
country: Burkina Faso
facility: Institute de Recherche en Sciences de la Sante, Direction Regionale de l'Ouest (IRSS-DRO) - / Centre Muraz
Study officials:
affiliation: Liverpool School of Tropical Medicine
name: Bernard J BRABIN, Professor
role: STUDY_DIRECTOR
affiliation: Clinical Research Unit Nanoro (CRUN)
name: Sabine GIES, MD, MTropMed, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brabin B, Tinto H, Roberts SA. Testing an infection model to explain excess risk of preterm birth with long-term iron supplementation in a malaria endemic area. Malar J. 2019 Nov 26;18(1):374. doi: 10.1186/s12936-019-3013-6.
citation: Brabin B, Gies S, Roberts SA, Diallo S, Lompo OM, Kazienga A, Brabin L, Ouedraogo S, Tinto H. Excess risk of preterm birth with periconceptional iron supplementation in a malaria endemic area: analysis of secondary data on birth outcomes in a double blind randomized controlled safety trial in Burkina Faso. Malar J. 2019 May 6;18(1):161. doi: 10.1186/s12936-019-2797-8.
citation: Diallo S, Roberts SA, Gies S, Rouamba T, Swinkels DW, Geurts-Moespot AJ, Ouedraogo S, Ouedraogo GA, Tinto H, Brabin BJ. Malaria early in the first pregnancy: Potential impact of iron status. Clin Nutr. 2020 Jan;39(1):204-214. doi: 10.1016/j.clnu.2019.01.016. Epub 2019 Jan 26.
citation: Gies S, Diallo S, Roberts SA, Kazienga A, Powney M, Brabin L, Ouedraogo S, Swinkels DW, Geurts-Moespot AJ, Claeys Y, D'Alessandro U, Tinto H, Faragher B, Brabin B. Effects of Weekly Iron and Folic Acid Supplements on Malaria Risk in Nulliparous Women in Burkina Faso: A Periconceptional, Double-Blind, Randomized Controlled Noninferiority Trial. J Infect Dis. 2018 Aug 24;218(7):1099-1109. doi: 10.1093/infdis/jiy257.
citation: Compaore A, Gies S, Brabin B, Tinto H, Brabin L. Community approval required for periconceptional adolescent adherence to weekly iron and/or folic acid supplementation: a qualitative study in rural Burkina Faso. Reprod Health. 2018 Mar 14;15(1):48. doi: 10.1186/s12978-018-0490-y.
citation: Brabin L, Roberts SA, Gies S, Nelson A, Diallo S, Stewart CJ, Kazienga A, Birtles J, Ouedraogo S, Claeys Y, Tinto H, d'Alessandro U, Faragher EB, Brabin B. Effects of long-term weekly iron and folic acid supplementation on lower genital tract infection - a double blind, randomised controlled trial in Burkina Faso. BMC Med. 2017 Nov 23;15(1):206. doi: 10.1186/s12916-017-0967-5.