Clinical trial NCT06327646: Maternal Adherence to MMS in Nepal
Official title: Non-inferiority Assessment of Maternal Adherence to Supplementation: a Trial on the Effects of MMS
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Supplementation
Keywords: Multiple Micronutrient Supplementation
Iron Folic Acid
Pregnancy
Lactation
Lead sponsor: Helen Keller International
Sponsor class: OTHER
Collaborators: name: Eleanor Crook Foundation
name: Johns Hopkins University
First posted: 2024-03-25
Enrollment: 2640
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: 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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: Pregnancy supplementation for 180 days: binary
timeFrame: Delivery
measure: Pregnancy supplementation for 180 days: continuous
timeFrame: Delivery
Secondary outcomes:
measure: Full pregnancy supplementation: binary
timeFrame: Delivery
measure: Full pregnancy supplementation: continuous
timeFrame: Delivery
measure: MMS supplementation for 180 days: Binary
timeFrame: Delivery
measure: MMS supplementation for 180 days: continuous
timeFrame: Delivery
measure: Antenatal Care Utilization: binary
timeFrame: Delivery
measure: Antenatal Care Utilization: continuous
timeFrame: Delivery
Other outcomes:
measure: Pregnancy supplementation for 30 days: binary
timeFrame: 30 days post enrollment/pill eligibility
measure: Pregnancy supplementation for 90 days: binary
timeFrame: 90 days post enrollment/pill eligibility
measure: Postpartum supplementation for 45 days: binary
timeFrame: 45 days post delivery
measure: Pregnancy supplementation for 30 days: continuous
timeFrame: 30 days post enrollment/pill eligibility
measure: Pregnancy supplementation for 90 days: continuous
timeFrame: 90 days post enrollment/pill eligibility
measure: Postpartum supplementation for 45 days: continuous
timeFrame: 45 days post delivery
measure: Supplement acceptability at 30-days: continuous
timeFrame: 30-days post enrollment
measure: Supplement acceptability at 90-days: continuous
timeFrame: 90-days post enrollment
measure: Supplement acceptability at 180-days: continuous
timeFrame: Delivery
measure: Supplement acceptability at 45-days post-partum: continuous
timeFrame: 45-days post partum
Locations:
city: Arghakhanchi
country: Nepal
facility: Thada primary health care centre
state: Lumbini Province
city: Banke
country: Nepal
facility: Banakatawa primary health care centre
state: Lumbini Province
city: Banke
country: Nepal
facility: Banakatti health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Basudevapur health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Bejapur health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Belahari health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Betahani health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Chisapani health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Ganapur health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Gangapur health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Hirminiya health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Holiya health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Indrapur health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Jaispur health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Kalaphata health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Kathkuiya health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Khajura primary health care centre
state: Lumbini Province
city: Banke
country: Nepal
facility: Khaskarkado health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Laxmanpur primary health care centre
state: Lumbini Province
city: Banke
country: Nepal
facility: Matahiya health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Narainapur health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Phattepur health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Puraina health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Puraini health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Rainyapur health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Saigaun Health Post
state: Lumbini Province
city: Banke
country: Nepal
facility: Sonpur health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Titihiriya health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Udarapur health post
state: Lumbini Province
city: Banke
country: Nepal
facility: Udayapur health post
state: Lumbini Province
city: Bardiya
country: Nepal
facility: Khairapur health post
state: Lumbini Province
city: Bardiya
country: Nepal
facility: Mathura haridwar health post
state: Lumbini Province
city: Bardiya
country: Nepal
facility: Motipur health post
state: Lumbini Province
city: Bardiya
country: Nepal
facility: Neulapur health Post
state: Lumbini Province
city: Bardiya
country: Nepal
facility: Sanoshree health post
state: Lumbini Province
city: Dang
country: Nepal
facility: Gadhawa Health Post
state: Lumbini Province
city: Dang
country: Nepal
facility: Hapur Health Post
state: Lumbini Province
city: Dang
country: Nepal
facility: Lalmatiya Health Post
state: Lumbini Province
city: Dang
country: Nepal
facility: Laxmipur Health Post
state: Lumbini Province
city: Dang
country: Nepal
facility: Satbariya Health Post
state: Lumbini Province
city: Dang
country: Nepal
facility: Shantinagar Health Post
state: Lumbini Province
city: Dang
country: Nepal
facility: Sisahaniya Health Post
state: Lumbini Province
city: Kapilvastu
country: Nepal
facility: Baskhor health post
state: Lumbini Province
city: Kapilvastu
country: Nepal
facility: Birpur health post
state: Lumbini Province
city: Kapilvastu
country: Nepal
facility: Chanai Health Post
state: Lumbini Province
city: Kapilvastu
country: Nepal
facility: Ganeshpur health post
state: Lumbini Province
city: Kapilvastu
country: Nepal
facility: Gugauli health post
state: Lumbini Province
city: Kapilvastu
country: Nepal
facility: Haranampur primary health care centre
state: Lumbini Province
city: Kapilvastu
country: Nepal
facility: Hariharpur healthpost
state: Lumbini Province
city: Kapilvastu
country: Nepal
facility: Jahadi health post
state: Lumbini Province
city: Kapilvastu
country: Nepal
facility: Krishnanagar health post
state: Lumbini Province
city: Kapilvastu
country: Nepal
facility: Labani health post
state: Lumbini Province
city: Kapilvastu
country: Nepal
facility: Maharajgunj primary health care centre
state: Lumbini Province
city: Kapilvastu
country: Nepal
facility: Motipur health post
state: Lumbini Province
city: Kapilvastu
country: Nepal
facility: Pakadi health post
state: Lumbini Province
city: Kapilvastu
country: Nepal
facility: Patariya health post
state: Lumbini Province
city: Kapilvastu
country: Nepal
facility: Pathardeiya health post
state: Lumbini Province
city: Kapilvastu
country: Nepal
facility: Shivapur health post
state: Lumbini Province
city: Kapilvastu
country: Nepal
facility: Sisawa health post
state: Lumbini Province
city: Kapilvastu
country: Nepal
facility: Tilaurakot health post
state: Lumbini Province
city: Nawalparasi west
country: Nepal
facility: Jagnnathpur Primary Health Care Centre
state: Lumbini Province
city: Nawalparasi west
country: Nepal
facility: Paklihawa health post
state: Lumbini Province
city: Pyuthan
country: Nepal
facility: Arkha Health Post
state: Lumbini Province
city: Pyuthan
country: Nepal
facility: Bangeshal Health Post
state: Lumbini Province
city: Pyuthan
country: Nepal
facility: Bhingri Primary Health Care Centre
state: Lumbini Province
city: Pyuthan
country: Nepal
facility: Damri Health Post
state: Lumbini Province
city: Pyuthan
country: Nepal
facility: Devisthan Health Post
state: Lumbini Province
city: Pyuthan
country: Nepal
facility: Okharkot Health Post
state: Lumbini Province
city: Pyuthan
country: Nepal
facility: Phopli Health Post
state: Lumbini Province
city: Pyuthan
country: Nepal
facility: Rajwara Health Post
state: Lumbini Province
city: Pyuthan
country: Nepal
facility: Sapdanda Health Post
state: Lumbini Province
city: Pyuthan
country: Nepal
facility: Syauliwang Health Post
state: Lumbini Province
city: Rolpa
country: Nepal
facility: Aresh Health Post
state: Lumbini Province
city: Rolpa
country: Nepal
facility: Holeri Phc
state: Lumbini Province
city: Rolpa
country: Nepal
facility: Liwang Health Post
state: Lumbini Province
city: Rolpa
country: Nepal
facility: Nerpa Health Post
state: Lumbini Province
city: Rolpa
country: Nepal
facility: Nuwagaun Health Post
state: Lumbini Province
city: Rolpa
country: Nepal
facility: Pakhapani Health Post
state: Lumbini Province
city: Rolpa
country: Nepal
facility: Pang Health Post
state: Lumbini Province
city: Rolpa
country: Nepal
facility: Rank Health Post
state: Lumbini Province
city: Rolpa
country: Nepal
facility: Sirpa Health Post
state: Lumbini Province
city: Rolpa
country: Nepal
facility: Sulichaur Phc
state: Lumbini Province
city: Rukum east
country: Nepal
facility: Hukam Health Post
state: Lumbini Province
city: Rukum east
country: Nepal
facility: Kankri Health Post
state: Lumbini Province
city: Rukum east
country: Nepal
facility: Pokhara Health Post
state: Lumbini Province
city: Rukum east
country: Nepal
facility: Sisne Health Post
state: Lumbini Province
city: Rukum east
country: Nepal
facility: Taksera Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Aama Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Amuwa (Paschhim) Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Asurena Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Bhagawanpur Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Bodabar Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Chhapiya Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Dhakadhai Primary Health Care Centre
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Dhamauli Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Ekala Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Farena Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Gajedi Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Gonaha Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Harnaiya Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Jogada Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Kamahariya Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Karmahawa Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Khudabagar Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Lumbini Primary Health Care Centre
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Majhagawa Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Manmateriya Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Masina Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Motipur primary health care centre
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Parroha Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Roinihawa Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Rudrapur Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Sadi Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Sakraun Pakadi Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Semara Bazar Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Shankarnagar Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Sikatahan Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Sipawa Health Post
state: Lumbini Province
city: Rupandehi
country: Nepal
facility: Tenuhawa Health Post
state: Lumbini Province
Study officials:
affiliation: Helen Keller International
name: Rolf Klemm, PhD
role: STUDY_DIRECTOR
References: