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: Active, not recruiting
• Conditions: Supplementation
• 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)?
5. What is the validity of women's recall of the amount of MMS/IFA received and of adherence to MMS/IFA compared to a gold standard?

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-, delivery (180-) and 45-days post-partum (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 pregnant women who health workers identify as meeting study criteria and who provide verbal informed consent to be study participants. When a woman reports for antenatal care to a health facility that is part of the RCT, the health worker will identify whether she is at least 18 years and no more than 35 years of age. If so, the health work will start to complete an enrollment log (Annex 4) to document the pregnant woman's details such as name, phone number, other household members' phone number(s), and house location details. This enrollment log also includes the study eligibility criteria (specified below) to help the health worker know if the woman could participate 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 detailed information on supplementation including its timing, benefits, and potential side effects. The enrollment log thus will generate a record of all pregnant women considered for the study, those excluded by each of the study inclusion criteria, and the refusal rate for the study, based on the health worker's initial screening. The health worker will share information for each pregnant woman deemed to meet study inclusion criteria and who agrees to participate in the study with the enumerator assigned to that particular health facility, following a communication protocol (Annex 5). The enumerator will, in turn, enter the woman's data into his/her electronic enrolment log, visit the woman at her home to verify her eligibility based on the inclusion/exclusion criteria, and obtain her written informed consent. For those women who are confirmed to meet study inclusion/exclusion criteria and provide their written informed consent to participate, the enumerator will then administer the enrollment survey. Pregnant women enrolled in the study who continue to provide consent and remain in the study will be further interviewed at 30 and 90-days post enrollment, as well as at delivery (approximately 180-days post enrollment) and 45-days post-partum (approximately 225-days post enrollment)

The recruitment of pregnant women will continue in each health center facility on a rolling basis until the targeted number of women (2,640) total are enrolled. Recruitment is anticipated to take approximately 8 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 . Additional delays in recruitment may occur due to adverse weather, greater clarity on pregnancy rates once enrollment starts, and other factors

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

Contacts and Locations

Study Locations

• Nepal
  • Lumbini Province
    • Arghakhanchi, Lumbini Province, Nepal
      • Thada primary health care centre
    • Banke, Lumbini Province, Nepal
      • Banakatawa primary health care centre
    • Banke, Lumbini Province, Nepal
      • Banakatti health post
    • Banke, Lumbini Province, Nepal
      • Basudevapur health post
    • Banke, Lumbini Province, Nepal
      • Bejapur health post
    • Banke, Lumbini Province, Nepal
      • Belahari health post
    • Banke, Lumbini Province, Nepal
      • Betahani health post
    • Banke, Lumbini Province, Nepal
      • Chisapani health post
    • Banke, Lumbini Province, Nepal
      • Ganapur health post
    • Banke, Lumbini Province, Nepal
      • Gangapur health post
    • Banke, Lumbini Province, Nepal
      • Hirminiya health post
    • Banke, Lumbini Province, Nepal
      • Holiya health post
    • Banke, Lumbini Province, Nepal
      • Indrapur health post
    • Banke, Lumbini Province, Nepal
      • Jaispur health post
    • Banke, Lumbini Province, Nepal
      • Kalaphata health post
    • Banke, Lumbini Province, Nepal
      • Kathkuiya health post
    • Banke, Lumbini Province, Nepal
      • Khajura primary health care centre
    • Banke, Lumbini Province, Nepal
      • Khaskarkado health post
    • Banke, Lumbini Province, Nepal
      • Laxmanpur primary health care centre
    • Banke, Lumbini Province, Nepal
      • Matahiya health post
    • Banke, Lumbini Province, Nepal
      • Narainapur health post
    • Banke, Lumbini Province, Nepal
      • Phattepur health post
    • Banke, Lumbini Province, Nepal
      • Puraina health post
    • Banke, Lumbini Province, Nepal
      • Puraini health post
    • Banke, Lumbini Province, Nepal
      • Rainyapur health post
    • Banke, Lumbini Province, Nepal
      • Saigaun Health Post
    • Banke, Lumbini Province, Nepal
      • Sonpur health post
    • Banke, Lumbini Province, Nepal
      • Titihiriya health post
    • Banke, Lumbini Province, Nepal
      • Udarapur health post
    • Banke, Lumbini Province, Nepal
      • Udayapur health post
    • Bardiya, Lumbini Province, Nepal
      • Khairapur health post
    • Bardiya, Lumbini Province, Nepal
      • Mathura haridwar health post
    • Bardiya, Lumbini Province, Nepal
      • Motipur health post
    • Bardiya, Lumbini Province, Nepal
      • Neulapur health Post
    • Bardiya, Lumbini Province, Nepal
      • Sanoshree health post
    • Dang, Lumbini Province, Nepal
      • Gadhawa Health Post
    • Dang, Lumbini Province, Nepal
      • Hapur Health Post
    • Dang, Lumbini Province, Nepal
      • Lalmatiya Health Post
    • Dang, Lumbini Province, Nepal
      • Laxmipur Health Post
    • Dang, Lumbini Province, Nepal
      • Satbariya Health Post
    • Dang, Lumbini Province, Nepal
      • Shantinagar Health Post
    • Dang, Lumbini Province, Nepal
      • Sisahaniya Health Post
    • Kapilvastu, Lumbini Province, Nepal
      • Baskhor health post
    • Kapilvastu, Lumbini Province, Nepal
      • Birpur health post
    • Kapilvastu, Lumbini Province, Nepal
      • Chanai Health Post
    • Kapilvastu, Lumbini Province, Nepal
      • Ganeshpur health post
    • Kapilvastu, Lumbini Province, Nepal
      • Gugauli health post
    • Kapilvastu, Lumbini Province, Nepal
      • Haranampur primary health care centre
    • Kapilvastu, Lumbini Province, Nepal
      • Hariharpur healthpost
    • Kapilvastu, Lumbini Province, Nepal
      • Jahadi health post
    • Kapilvastu, Lumbini Province, Nepal
      • Krishnanagar health post
    • Kapilvastu, Lumbini Province, Nepal
      • Labani health post
    • Kapilvastu, Lumbini Province, Nepal
      • Maharajgunj primary health care centre
    • Kapilvastu, Lumbini Province, Nepal
      • Motipur health post
    • Kapilvastu, Lumbini Province, Nepal
      • Pakadi health post
    • Kapilvastu, Lumbini Province, Nepal
      • Patariya health post
    • Kapilvastu, Lumbini Province, Nepal
      • Pathardeiya health post
    • Kapilvastu, Lumbini Province, Nepal
      • Shivapur health post
    • Kapilvastu, Lumbini Province, Nepal
      • Sisawa health post
    • Kapilvastu, Lumbini Province, Nepal
      • Tilaurakot health post
    • Nawalparasi west, Lumbini Province, Nepal
      • Jagnnathpur Primary Health Care Centre
    • Nawalparasi west, Lumbini Province, Nepal
      • Paklihawa health post
    • Pyuthan, Lumbini Province, Nepal
      • Arkha Health Post
    • Pyuthan, Lumbini Province, Nepal
      • Bangeshal Health Post
    • Pyuthan, Lumbini Province, Nepal
      • Bhingri Primary Health Care Centre
    • Pyuthan, Lumbini Province, Nepal
      • Damri Health Post
    • Pyuthan, Lumbini Province, Nepal
      • Devisthan Health Post
    • Pyuthan, Lumbini Province, Nepal
      • Okharkot Health Post
    • Pyuthan, Lumbini Province, Nepal
      • Phopli Health Post
    • Pyuthan, Lumbini Province, Nepal
      • Rajwara Health Post
    • Pyuthan, Lumbini Province, Nepal
      • Sapdanda Health Post
    • Pyuthan, Lumbini Province, Nepal
      • Syauliwang Health Post
    • Rolpa, Lumbini Province, Nepal
      • Aresh Health Post
    • Rolpa, Lumbini Province, Nepal
      • Holeri Phc
    • Rolpa, Lumbini Province, Nepal
      • Liwang Health Post
    • Rolpa, Lumbini Province, Nepal
      • Nerpa Health Post
    • Rolpa, Lumbini Province, Nepal
      • Nuwagaun Health Post
    • Rolpa, Lumbini Province, Nepal
      • Pakhapani Health Post
    • Rolpa, Lumbini Province, Nepal
      • Pang Health Post
    • Rolpa, Lumbini Province, Nepal
      • Rank Health Post
    • Rolpa, Lumbini Province, Nepal
      • Sirpa Health Post
    • Rolpa, Lumbini Province, Nepal
      • Sulichaur Phc
    • Rukum east, Lumbini Province, Nepal
      • Hukam Health Post
    • Rukum east, Lumbini Province, Nepal
      • Kankri Health Post
    • Rukum east, Lumbini Province, Nepal
      • Pokhara Health Post
    • Rukum east, Lumbini Province, Nepal
      • Sisne Health Post
    • Rukum east, Lumbini Province, Nepal
      • Taksera Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Aama Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Amuwa (Paschhim) Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Asurena Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Bhagawanpur Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Bodabar Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Chhapiya Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Dhakadhai Primary Health Care Centre
    • Rupandehi, Lumbini Province, Nepal
      • Dhamauli Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Ekala Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Farena Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Gajedi Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Gonaha Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Harnaiya Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Jogada Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Kamahariya Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Karmahawa Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Khudabagar Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Lumbini Primary Health Care Centre
    • Rupandehi, Lumbini Province, Nepal
      • Majhagawa Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Manmateriya Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Masina Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Motipur primary health care centre
    • Rupandehi, Lumbini Province, Nepal
      • Parroha Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Roinihawa Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Rudrapur Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Sadi Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Sakraun Pakadi Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Semara Bazar Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Shankarnagar Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Sikatahan Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Sipawa Health Post
    • Rupandehi, Lumbini Province, Nepal
      • Tenuhawa Health Post

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria

To be eligible for the study, health facilities must meet four criteria:

1. public/government-run;
2. either a PHCC or HP at point of randomization;
3. implement the standard ANC package of care; and
4. have the top 50% average monthly caseloads for newly enrolled pregnant women (i.e. first ANC) for that specific agro-ecological zone (mountains - at least 5/month; hill - at least 8/month; and terai - at least 15/month) based on health management information system (HMIS) ANC data (July 16, 2021, to July 15, 2022).

To be eligible for the study, pregnant women must meet multiple criteria, at the point of enrollment:

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 at least 12 but not yet 14 weeks at time of health facility enrollment, estimated based on her last menstrual period (LMP) with exact calendar calculation confirmed during visit by enumerator;
4. pregnancy without any complications; not classified as severe anemic as well as high-risk pregnancy (i.e. not having the following conditions: diabetes, polycystic ovary syndrome, thyroid disease, kidney diseases, fibroids and severe mental/physical conditions that prevent study participation including unable to speak, attend ANC/PNC, take supplements or mental/cognitive impairment);
5. provides written informed consent to participate in the study; and
6. agrees to have 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
Pregnancy supplementation for 180 days: binary	Consumed at least 180 supplement tablets between study enrollment and delivery (MMS-blister vs IFA-blister; MMS-bottle vs. IFA blister)	Delivery
Pregnancy supplementation for 180 days: continuous	Number of supplements consumed between study enrollment and delivery (MMS-blister vs IFA-blister; MMS-bottle vs. IFA blister)	Delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Full pregnancy supplementation: binary	Consumed at least the maximum number of supplement tablets eligible to consume between study enrollment and delivery (MMS-blister vs IFA-blister; MMS-bottle vs. IFA blister; MMS-bottle vs MMS-blister)	Delivery
Full pregnancy supplementation: continuous	Number of supplements consumed between study enrollment and delivery (MMS-blister vs IFA-blister; MMS-bottle vs. IFA blister; MMS-bottle vs MMS-blister)	Delivery
MMS supplementation for 180 days: Binary	Consumed at least 180 supplement tablets between study enrollment and delivery (MMS-blister vs MMS-bottle)	Delivery
MMS supplementation for 180 days: continuous	Number of supplements consumed between study enrollment and delivery (MMS-blister vs. MMS-bottle)	Delivery
Antenatal Care Utilization: binary	Received the recommended 8 ANC visits during pregnancy or not (MMS-blister vs MMS-bottle)	Delivery
Antenatal Care Utilization: continuous	Number of ANC visits during pregnancy (MMS-blister vs. MMS-bottle)	Delivery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pregnancy supplementation for 30 days: binary	Consumed at least 30 supplement tablets between study enrollment and 30 days later during pregnancy (IFA-blister vs MMS-blister; IFA-blister vs MMS-bottle; MMS-blister vs MMS-bottle)	30 days post enrollment/pill eligibility
Pregnancy supplementation for 90 days: binary	Consumed at least 90 supplement tablets between study enrollment and 30 day follow-up visit during pregnancy (IFA-blister vs MMS-blister; IFA-blister vs MMS-bottle; MMS-blister vs MMS-bottle)	90 days post enrollment/pill eligibility
Postpartum supplementation for 45 days: binary	Consumed at least 45 supplement tablets between delivery and 45 days later (IFA-blister vs MMS-blister; IFA-blister vs MMS-bottle; MMS-blister vs MMS-bottle)	45 days post delivery
Pregnancy supplementation for 30 days: continuous	Number of supplements consumed between study enrollment and 30 days later (IFA-blister vs MMS-blister; IFA-blister vs MMS-bottle; MMS-blister vs MMS-bottle)	30 days post enrollment/pill eligibility
Pregnancy supplementation for 90 days: continuous	Number of supplements consumed between study enrollment and 90 days later (IFA-blister vs MMS-blister; IFA-blister vs MMS-bottle; MMS-blister vs MMS-bottle)	90 days post enrollment/pill eligibility
Postpartum supplementation for 45 days: continuous	Number of supplements consumed between delivery and 45 days later (IFA-blister vs MMS-blister; IFA-blister vs MMS-bottle; MMS-blister vs MMS-bottle)	45 days post delivery
Supplement acceptability at 30-days: continuous	Degree of acceptability of supplements measured as a sum (0-25) from a 5-point likert scale for each property (taste, color, swallowability, odor, and frequency) 30-days post-enrollment (IFA-blister vs MMS-blister; IFA-blister vs MMS-bottle; MMS-blister vs MMS-bottle)	30-days post enrollment
Supplement acceptability at 90-days: continuous	Degree of acceptability of supplements measured as a sum (0-25) from a 5-point likert scale for each property (taste, color, swallowability, odor, and frequency) 90-days post-enrollment (IFA-blister vs MMS-blister; IFA-blister vs MMS-bottle; MMS-blister vs MMS-bottle)	90-days post enrollment
Supplement acceptability at 180-days: continuous	Degree of acceptability of supplements measured as a sum (0-25) from a 5-point likert scale for each property (taste, color, swallowability, odor, and frequency) after delivery (IFA-blister vs MMS-blister; IFA-blister vs MMS-bottle; MMS-blister vs MMS-bottle)	Delivery
Supplement acceptability at 45-days post-partum: continuous	Degree of acceptability of supplements measured as a sum (0-25) from a 5-point likert scale for each property (taste, color, swallowability, odor, and frequency), at 45 days post-partum (IFA-blister vs MMS-blister; IFA-blister vs MMS-bottle; MMS-blister vs MMS-bottle)	45-days post partum

Collaborators and Investigators

• Sponsor: Helen Keller International
• Collaborators: Johns Hopkins University; Eleanor Crook Foundation
• Investigators: Study Director: Rolf Klemm, PhD, Helen Keller International

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2024
• Primary Completion (Estimated): July 24, 2025
• Study Completion (Estimated): September 1, 2025

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, 2025
• Last Update Submitted That Met QC Criteria: January 27, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Pregnancy; Lactation; Multiple Micronutrient Supplementation; Iron Folic Acid
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Vitamin B Complex; Vitamins; Hematinics; Folic Acid; Micronutrients; Trace Elements
• 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
• product manufactured in and exported from the U.S.: No