Maternal Adherence to MMS in Nepal (NAMASTE MMS)

Non-inferiority Assessment of Maternal Adherence to Supplementation: A Trial on the Effects of MMS

Although clinical studies highlight the value of MMS for pregnant and lactating women, implementation research studies are necessary to understand adherence and acceptability to the product and to uncover potential obstacles to implementation in specific contexts. For Nepal, it is crucial to establish whether adherence to MMS supplementation is non-inferior to the existing IFA supplementation for 180 tablets, which has a high (65%) adherence rate. It is also important to investigate how whether providing MMS in bottles (containing a substantial quantity, such as 90 count bottles twice during pregnancy) might impact ANC utilization, particularly in terms of ensuring that pregnant women attend at least eight ANC visits. Furthermore, assessment of MMS acceptability, including pill taste, smell, size, swallowability, side effects, benefits as well as aspects such as product labeling and packaging, among end users in Nepal, is needed to understand acceptability of MMS vs. IFA. Finally, implementation issues within the health system, including the need of trainings for healthcare workers' and, female community health volunteers (FCHVs)' training needs; and government stakeholders' interest and barriers;; community s Social and behavioral change communication needs, and issues around supply chain issues should be well-understood and documented to inform prior to scale-up to support a smooth transition of MMS. Thus, Helen Keller International, in collaboration with Nepal's Ministry of Health and Population (MoHP) and the Eleanor Crook Foundation (ECF), will conduct a set of four mixed-methods studies to generate evidence and insights that inform the development of an MMS supplementation strategy. This trial in one province of Nepal is the first study that will be complemented by one additional quantitative study and two qualitative studies to generate evidence on the topics mentioned.

Study Overview

• Status: Not yet recruiting
• Conditions: Pregnancy Related; Supplementation; Postnatal Related
• Intervention / Treatment: Drug: Iron Folic Acid Blister; Drug: Multiple Micronutrient Supplement Blister; Drug: Multiple Micronutrient Supplement Bottle

Detailed Description

The primary and secondary research questions for the randomized controlled trial named "Non-inferiority Assessment of Maternal Adherence to Supplementation: A Trial of the Effects of MMS" (NAMASTE MMS) are detailed below:

Primary:

1. Is adherence to the full prescription of 180 MMS (-blister) during pregnancy non-inferior to adherence to the full prescription of 180 IFA-blister during pregnancy (arm 2 vs arm 1)?
2. Is adherence to the full prescription of 180 MMS (-bottle) during pregnancy non-inferior to adherence to the full prescription of 180 IFA-blister during pregnancy (arm 3 vs arm 1)?

Secondary:

1. Is the level of adherence to MMS-blister and MMS-bottle non-inferior to the level of adherence to IFA-blister at different points during pregnancy and lactation (i.e. 30 days, 90 days, and 45 days postpartum from start of supplementation) (arm 2 vs. arm 1 and arm 3 vs arm 1)?
2. Is there a difference in adherence to 180 MMS during pregnancy from blister packaging vs bottle packaging of MMS (arm 2 vs arm 3?
3. Is there a difference in adherence to ANC visits during pregnancy from blister packaging vs bottle packaging of MMS (arm 2 vs arm 3)?
4. What is the level of acceptability of IFA and MMS at different stages of pregnancy (i.e. 30 days, 90 days, 180 days, and 45 days postpartum) (arms 1, 2 and 3)?

This c-RCT will be conducted among pregnant women assigned to one of three trial arms (as described below in the section on interventional description). Data will be collected via in-person surveys at their home over a period of 12 months, including immediately following the 30-, 90-, 180- and 225-day points post-enrollment at the pregnant woman's first antenatal care visit.

The c-RCT will be conducted in Lumbini Province of Nepal, which was purposely selected among the four provinces that cover all three agro-ecological regions in Nepal: mountains, hills, and the terai (plains) due to ease of implementation. The random sampling of health facilities (clusters) will be as proportional to the population as possible - i.e., 10% from mountains, 40% from hills, and 50% from terai. The required facilities (n=120) will be randomly selected and assigned to one of the three c-RCT arms using from the list of government health facilities (primary health care centers (PHCCs), and health posts (HPs) only).

A total of 120 health facilities will be randomly assigned to one of the three arms. Forty (40) health facilities will receive IFA in blister packs (current standard of care), 40 health facilities will receive MMS in blister packs, and 40 will receive MMS in bottles, and 40 will receive IFA in blister packs. These supplements will be distributed to study participants only. When a pregnant woman reports for her first antenatal care visit to a health facility that is part of the RCT, the health worker will use eligibility criteria (specified below)gestational age of not more than 14 weeks at time of enrollment; pregnancy without any complications at first ANC visit; not classified as a high-risk pregnancy - not having the following conditions: diabetes, polycystic ovary syndrome, thyroid disease, kidney diseases, fibroids) to assess her eligibility for inclusion in the study. If she is deemed eligible, the health worker will inform her about the study and the opportunity to participate including the research objectives and processes and share, a detailed brief information onf supplementationMMS includingand its timing, benefits, and potential side effects, and a summary of the evidence on its effectiveness. The record of all pregnant women considered for the study and of the eligible women for inclusion in the study will be maintained in an enrolment log (Annex - 4). If theFor each womaen who expresses her willingness to participate in the study, the health worker will document her extra details in the separateregister her details in the study enrollment log, i provided by the study team, including her name, phone number, other household members' phone number(s), and house location details. This information will be shared with enumerators assigned to that health centerfacility . These enumerators will then contact visit the woman at her home to verify her eligibility based on the inclusion/exclusion criteria, . Enumerators will then visit the pregnant women at their respective houses, obtain written informed consent, and administer the enrollment questionssurvey. Subsequently, each pregnant woman will be revisited at their home at 30, 90, 180, and 225 -days post-enrollment for data collection.

The recruitment of pregnant women will continue in each health center facility on a rolling basis until the targeted number of women are enrolled. Recruitment is anticipated to take approximately 3 months, with quicker data collection in the plains given a larger number of pregnant women using services from these facilities and progressively slower data collection in the hills and mountains, due to lower population and in turn, less frequent pregnancies, and service usage .

• Study Type: Interventional
• Enrollment (Estimated): 2640
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. be 18 - 35 completed years of age at health facility enrollment;
2. not planning to move/migrate for at least nine months after enrollment ;
3. gestational age of not more than 14 weeks at time of health facility enrollment, estimated based on her last menstrual period (LMP);
4. pregnancy without any complications at first ANC visit; not classified as a high-risk pregnancy (i.e. not having the following conditions: diabetes, polycystic ovary syndrome, thyroid disease, kidney diseases, fibroids);
5. provides written informed consent to participate in the study; and
6. is willing to have data collectorsenumerators visit the home at different data collection points.

Exclusion Criteria:

1. younger than 18 or older than 35 completed years of age at health facility enrollment;
2. planning to move/migrate for at least nine months after enrollment ;
3. gestational age of more than 14 weeks at time of health facility enrollment, estimated based on her last menstrual period (LMP);
4. pregnancy with complications at first ANC visit; classified as a high-risk pregnancy (i.e. having any of the following conditions: diabetes, polycystic ovary syndrome, thyroid disease, kidney diseases, fibroids; anemia);
5. does not provide written informed consent to participate in the study; and
6. is not willing to have data collectors/enumerators visit the home at different data collection points.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: IFA-180 (Blister)	Drug: Iron Folic Acid Blister; Standard of Care - IFA in a blister pack along with related job aids, counselling during ANC, etc.
Experimental: MMS-180 (Blister)	Drug: Multiple Micronutrient Supplement Blister; MMS in a blister pack along with related job aids, counselling during ANC, etc.
Experimental: MMS-180 (Bottle)	Drug: Multiple Micronutrient Supplement Bottle; MMS in bottles along with related job aids, counselling during ANC, etc.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
180 days adherence: MMS (2 types) vs. IFA	Measured in two ways: 1) the percentage of tablets (IFA or MMS) consumed at the end of pregnancy divided by 180 (total eligible during pregnancy), for all three groups arms and 2) the percentage of tablets (IFA or MMS) consumed at the end of pregnancy divided by the number of tables (IFA or MMS) eligible to receive based on first ANC visit, LMP date, and early delivery and similar factors, for all three groups . For generating the number of pills consumed, we will count the total number of tablets. We will generate the average adherence rate for each arm, by adding up the individual adherence rates for all participants in each arm and dividing by the total number of participants.	180 days post enrollment/pill eligibility

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30, 90, and 225 days adherence	Measured in two ways: 1) the percentage of tablets (IFA or MMS) consumed at the time point (30, 90, and 225 days), divided by the total eligible during that time point (30, 90, and 225) for all three groups arms and 2) the percentage of tablets (IFA or MMS) consumed at each time point (30, 90, and 225 days) divided by the number of tables (IFA or MMS) received for that period, for all three groups . For generating the number of pills consumed, we will count the total number of tablets. We will generate the average adherence rate for each arm, by adding up the individual adherence rates for all participants in each arm and dividing by the total number of participants.	30, 90 and 225 days post enrollment/pill eligibility
180 adherence: MMS blister vs MMS bottle	Measured as the percentage of tablets (MMS) consumed at the end of pregnancy (180 days), for both MMS blister and MMS bottle arms. For this, we will count the total number of tablets each woman consumed and divide this count by the number of pills the woman was eligible to take at the time of the survey, generating an individual adherence rate per woman. We will generate the average adherence rate for each arm, by adding up these rates for all participants in each arm and dividing by the total participants. Based on these rates, we'll set thresholds for low, middle, and high adherence levels.	180 days post enrollment/eligibility
MMS acceptability	Measured using a 5- point Likert scale on longitudinal organoleptic surveys on five dimensions, (taste, color, swallowability, odor, and dosing frequency) , and other information such as information such as packaging, location, and size of information, with women in all three study arms at 30-, 90-, 180-and 225 days. An analysis will look at changes in acceptability over time in each arm and assess differences in acceptability between the three arms	30, 90, 180 and 225 days post enrollment/eligibility
Antenatal Care Utilization at 180 days	Measured in two ways: 1) as the mean number of visits to any health center for obtaining ANC checkups and 2) the prevalence of receiving the recommended 8 ANC contacts. This will be assessed by recording the information about ANC visits from the individual's antenatal careANC card. We will generate the mean utilization and prevalence of ANC utilization for each arm, by compiling data from all study participants in each arm and, for prevalence, dividing by the number of participants per arm and reporting a percentage of complete ANC utilization.	180 days post enrollment/eligibility

Collaborators and Investigators

• Sponsor: Helen Keller International
• Collaborators: Eleanor Crook Foundation

Study record dates

Study Major Dates

• Study Start (Estimated): April 20, 2024
• Primary Completion (Estimated): July 20, 2024
• Study Completion (Estimated): July 20, 2024

Study Registration Dates

• First Submitted: March 18, 2024
• First Submitted That Met QC Criteria: March 18, 2024
• First Posted (Actual): March 25, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Pregnancy; Lactation; Multiple Micronutrient Supplementation; Iron Folic Acid
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Vitamins; Vitamin B Complex; Hematinics; Micronutrients; Trace Elements; Folic Acid
• Other Study ID Numbers: 66677

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No