MMS-MAP: Multiple Micronutrient Supplementation for Maternal Anemia Prevention in Tanzania

Sponsor

George Washington University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06079918

Collaborator

Ifakara Health Institute (Other), Harvard School of Public Health (HSPH) (Other), Muhimbili University of Health and Allied Sciences (Other), Africa Academy for Public Health (Other), Columbia University (Other)

6,381

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This is an individually randomized controlled trial to assess the effect of multiple micronutrient supplements (MMS) containing 60 and 45 mg iron as compared to MMS containing 30 mg of iron (standard UNIMMAP formulation) on maternal moderate or severe anemia. This study will help inform countries like Tanzania that currently use IFA containing 60 mg of iron regarding the dose of iron to use in MMS.

Condition or Disease	Intervention/Treatment	Phase
Pregnancy Related	Dietary Supplement: Multiple Micronutrient Supplements with 30 mg of elemental iron Dietary Supplement: Multiple Micronutrient Supplements with 45 mg of elemental iron Dietary Supplement: Multiple Micronutrient Supplements with 60 mg of elemental iron	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

6381 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

The trial is quadruple blind with all trial participants, outcome assessors (research staff and care providers), investigators, and trials statistician and data analysts being unable to determine the allocated trial arm for any trial participant or identify trial participants who are on the same trial regimen.

Primary Purpose:

Prevention

Official Title:

Randomized Trial of Higher-dose Iron (60 mg, 45 mg) Compared to Low-dose Iron (30 mg) in Multiple Micronutrient Supplements in Pregnancy on Moderate and Severe Maternal Anemia

Anticipated Study Start Date :

Nov 1, 2023

Anticipated Primary Completion Date :

Jun 1, 2025

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: MMS with 30 mg iron MMS with standard UNIMMAP formulation of 15 micronutrients, including 30 mg of iron	Dietary Supplement: Multiple Micronutrient Supplements with 30 mg of elemental iron MMS with 30 mg iron is the active comparator group. The standard UNIMMAP MMS formulation includes 30 mg of iron which will be taken orally once daily from the time of randomization until delivery.
Experimental: MMS with 45 mg iron MMS with 45 mg of iron plus standard UNIMMAP formulation for other 14 micronutrients	Dietary Supplement: Multiple Micronutrient Supplements with 45 mg of elemental iron MMS with 45 mg iron is an intervention group. MMS with 45 mg of iron plus standard UNIMMAP formulation for other 14 micronutrients will be taken orally once daily from the time of randomization until delivery.
Experimental: MMS with 60 mg iron MMS with 60 mg of iron plus standard UNIMMAP formulation for other 14 micronutrients	Dietary Supplement: Multiple Micronutrient Supplements with 60 mg of elemental iron MMS with 60 mg iron is an intervention group. MMS with 60 mg of iron plus standard UNIMMAP formulation for other 14 micronutrients will be taken orally once daily from the time of randomization until delivery.

Arm

Intervention/Treatment

Active Comparator: MMS with 30 mg iron

MMS with standard UNIMMAP formulation of 15 micronutrients, including 30 mg of iron

Dietary Supplement: Multiple Micronutrient Supplements with 30 mg of elemental iron

MMS with 30 mg iron is the active comparator group. The standard UNIMMAP MMS formulation includes 30 mg of iron which will be taken orally once daily from the time of randomization until delivery.

Experimental: MMS with 45 mg iron

MMS with 45 mg of iron plus standard UNIMMAP formulation for other 14 micronutrients

Dietary Supplement: Multiple Micronutrient Supplements with 45 mg of elemental iron

MMS with 45 mg iron is an intervention group. MMS with 45 mg of iron plus standard UNIMMAP formulation for other 14 micronutrients will be taken orally once daily from the time of randomization until delivery.

Experimental: MMS with 60 mg iron

MMS with 60 mg of iron plus standard UNIMMAP formulation for other 14 micronutrients

Dietary Supplement: Multiple Micronutrient Supplements with 60 mg of elemental iron

MMS with 60 mg iron is an intervention group. MMS with 60 mg of iron plus standard UNIMMAP formulation for other 14 micronutrients will be taken orally once daily from the time of randomization until delivery.

Outcome Measures

Primary Outcome Measures

Proportion of pregnant women with third-trimester moderate or severe anemia [3rd trimester (weeks 27-42 of pregnancy)]
Defined as a hemoglobin concentration <10 g/dL.

Secondary Outcome Measures

Maternal hemoglobin concentration [3rd trimester (weeks 27-42 of pregnancy)]
Continuous hemoglobin concentration measured from venous blood by complete blood count
Maternal hemoglobin concentration [6 weeks postpartum]
Continuous hemoglobin concentration measured from venous blood by complete blood count
Proportion of pregnant women with anemia [3rd trimester (weeks 27-42 of pregnancy)]
Hb concentration < 11 g/dL
Proportion of postpartum women with anemia [6 weeks postpartum]
Hb concentration < 12 g/dL
Maternal serum ferritin [3rd trimester (weeks 27-42 of pregnancy)]
Continuous Inflammation-adjusted serum ferritin
Proportion of pregnant women with iron deficiency [3rd trimester (weeks 27-42 of pregnancy)]
Inflammation-adjusted serum ferritin < 15 ug/L
Proportion of pregnant women with iron deficiency anemia [3rd trimester (weeks 27-42 of pregnancy)]
Anemia (Hb < 10 g/dL) and iron deficiency (inflammation-adjusted serum ferritin < 15 ug/L)
Proportion of women with preeclampsia [From 20 weeks gestation through 42 days post delivery]
Gestational hypertension and gestational proteinuria among participants without chronic hypertension or gestational proteinuria among participants with chronic hypertension (superimposed preeclampsia) or clinical diagnosis of preeclampsia by managing clinical team or development of severe features of preeclampsia even in the absence of proteinuria
Proportion of women with antepartum bleeding [From 24 weeks gestation through delivery]
Self-reported or clinical diagnosis of bleeding from or into the genital tract
Proportion of women with postpartum hemorrhage [From 24 weeks gestation through 42 days post delivery]
Clinical diagnosis of postpartum hemorrhage or use of critical interventions to treat postpartum hemorrhage
Proportion of women with peripartum infection [During pregnancy through 42 days postpartum]
Infection in the peripartum period
Proportion of women with pregnancy-related death [During pregnancy through 42 days after pregnancy end]
Death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the cause of death
Proportion of women with symptoms consistent with depression [3rd trimester (weeks 27-42 of pregnancy)]
Patient Health Questionnaire-9 (PHQ-9) score ranging from 0 to 27, with higher number is consistent with depression and anxiety
Proportion of women with symptoms consistent with depression [6 weeks postpartum]
Patient Health Questionnaire-9 (PHQ-9) score ranging from 0 to 27, with higher number is consistent with depression and anxiety
Proportion of women with malaria infection [Pregnancy through 42 days postpartum]
Based on HRP2 biomarker and rapid-diagnostic tests (RDTs)
Proportion of fetal deaths [At pregnancy termination (weeks 1-40 of pregnancy)]
A product of human conception, irrespective of the duration of the pregnancy, which, after expulsion or extraction, does not breath or show any other evidence of life such as beating of the heart, pulsation of the umbilical cord, or definite movement of voluntary muscles, whether or not the umbilical cord has been cut or the placenta is attached
Proportion of stillbirths [At pregnancy termination (weeks 1-40 of pregnancy)]
Fetal death ≥ 28 weeks gestation
Birthweight [At birth]
Continuous birthweight among live births
Proportion of live birth with low birthweight [At birth]
Live birth with birthweight < 2500 g
Gestational age at birth [At birth]
Duration of gestation in weeks as a continuous measure among live births based on best obstetric estimate among live births
Proportion of preterm live births [At birth]
Live birth <37 weeks gestation (based on best obstetric estimate)
Birthweight for gestational age [At birth]
Continuous centile based on INTERGROWTH-21st standard birth centile among live births
Proportion of small-for-gestational age live births (<10th percentile) [At birth]
Size-for-gestational age <10th on the INTERGROWTH-21st standard among live births
Proportion of small-for-gestational age live births (<3rd percentile) [At birth]
Size-for-gestational age <3rd percentile on the INTERGROWTH-21st standard among live births
Infant hemoglobin concentration [At 6 weeks of age]
Continuous Hb concentration measured from capillary blood by complete blood count
Infant serum ferritin [At 6 weeks of age]
Continuous inflammation adjusted serum ferritin
Proportion of neonatal deaths [From birth to 28 days of age]
Death of liveborn infant during the first 28 completed days of life
Proportion of infant deaths < 42 days [From birth to 42 days of age]
Death of a live born infant during the first 42 completed days of life

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Attending first ANC visit at study clinics
Pregnant women < 20 weeks gestation (up to 19 weeks and 6 days) by last menstrual period (LMP)
Aged ≥ 18 years old
Intending to stay in Dar es Salaam until 6 weeks post delivery
Provides informed consent

Exclusion Criteria:

Severe anemia (defined as hemoglobin < 8.5 g/dL per Tanzania standard of care)
Sickle cell disease
Concurrently enrolled in another nutritional clinical trial

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

George Washington University
Ifakara Health Institute
Harvard School of Public Health (HSPH)
Muhimbili University of Health and Allied Sciences
Africa Academy for Public Health
Columbia University

Investigators

Principal Investigator: Blair Wylie, MD, MPH, Columbia University
Principal Investigator: Honorati Masanja, PhD, Ifakara Health Institute
Principal Investigator: Alfa Muhihi, PhD, Africa Academy for Public Health
Principal Investigator: Andreas Pembe, MD, MMed, PhD, FCOG, Muhimbili University of Health and Allied Sciences
Principal Investigator: Emily R Smith, ScD, MPH, The Goerge Washington University
Principal Investigator: Christopher R Sudfeld, ScD, ScM, Harvard University