A Phase III Double-Blind, Adaptive Randomized Trial of Antenatal MMSPlus Versus UNIMAPP MMS and Postnatal MMSPlus Versus UNIMAPP MMS or IFA to Improve Infant Birth Outcomes and Growth at 6 Months
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 3,000
- 试验地点
- 1
- 主要终点
- Antenatal Phase: Composite Infant Health Score at 28 Days Post-Birth
研究概览
简要总结
This clinical trial aims to learn if MMS Plus improves infant health compared to standard MMS during pregnancy and the postnatal period in women living in peri-urban areas of Karachi, Pakistan. It will also evaluate how MMS Plus affects infant growth during the first 6 months of life.
The main questions it aims to answer are:
- Does MMS Plus during pregnancy reduce the risk of poor infant outcomes compared to standard MMS, as measured on a 5-point ordinal scale ranging from perinatal mortality to term birth with appropriate, small, or large-for-gestational-age infants?
- Does postnatal MMS Plus improve infant length velocity at 6 months of age among exclusively breastfed infants compared to standard MMS and iron/folic acid (IFA) supplementation?
Researchers will compare:
- MMS Plus versus standard MMS during pregnancy (antenatal phase)
- MMS Plus versus standard MMS versus IFA after birth (postnatal phase)
Participants will:
- Be randomly assigned to receive either MMS Plus or standard MMS during pregnancy
- Be re-randomized after delivery to receive either MMS Plus, standard MMS, or IFA supplements during the postnatal period
- Receive supplements under double-blind conditions
- Be followed through childbirth and until the infant is 6 months of age
- Attend regular clinic visits for health monitoring, infant assessments, and data collection.
This phase III adaptive randomized controlled trial will occur in three peri-urban catchment areas of Karachi, Pakistan.
详细描述
This is a two-phase, Phase III double-blind, adaptive randomized controlled trial designed to evaluate the effects of enhanced multiple micronutrient supplementation (MMS Plus) compared to standard UNIMMAP MMS and iron/folic acid (IFA) supplementation on maternal and infant health outcomes in peri-urban Karachi, Pakistan. The trial is being conducted by The Aga Khan University and is funded by the Bill Gates Foundation.
Study Phases and Design:
Antenatal Phase:
Pregnant women between 8-14 weeks of gestation will be enrolled and randomized (1:1) into one of two arms:
MMS Plus (enhanced formulation) Standard MMS (UNIMMAP formulation)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 15 Years 至 49 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Gestational age confirmed by ultrasound to be 8-14 weeks
- •Singleton and viable fetus on ultrasound
- •A resident of the catchment area for at least the last six months
- •Plans to stay within the catchment area during the pregnancy duration, during delivery and after birth of the baby.
- •Has provided voluntary written informed consent
排除标准
- •Women with known allergies or intolerance to any components of the MMS or MMS PLUS being studied
- •Women with pre-existing health conditions such as history of uncontrolled diabetes and hypertension or other chronic illnesses
- •Substance abuse, such as recreational drugs or smoking tobacco. Women chewing tobacco will not be excluded.
- •Postnatal Phase::
- •Inclusion Criteria:
- •Birth weight available within 72 hours
- •Intention to breastfeed for 6 months
- •Resides in the study area for the duration of the trial
- •Has provided voluntary written informed consent
- •Exclusion Criteria:
- •Congenital anomalies, birth defects, or severe neonatal complications
- •Infants who are already receiving supplemental formula feeding or other nutritional supplements (except pre-lacteal feeding, vitamins, and medications)
- •Infants whose mothers have conditions that significantly affect breastfeeding, such as severe postpartum depression, insufficient milk supply, or maternal use of medications that contraindicate breastfeeding
研究组 & 干预措施
MMS
Once daily dose of MMS sachet + Standard ANC and nutrition counseling
干预措施: MMS (Dietary Supplement)
IFA
Once daily dose of IFA sachet + Standard postnatal care (PNC) and nutrition counseling
干预措施: IFA (Dietary Supplement)
MMS Plus
One daily sachet of MMS PLUS + Standard ANC and nutrition counseling
干预措施: MMS Plus (Drug)
结局指标
主要结局
Antenatal Phase: Composite Infant Health Score at 28 Days Post-Birth
时间窗: 28 days after birth
Infant health will be assessed using a 5-point ordinal categorical scale, defined as follows: Stillbirth, miscarriage, or early neonatal death (0-6 days); Preterm birth with Small for Gestational Age (SGA) infant; Preterm birth with Appropriate or Large for Gestational Age (AGA or LGA) infant; Term birth with SGA infant; Term birth with AGA or LGA infant Method of Aggregation: Proportion of participants in each outcome category Analysis Metric: Ordinal regression (e.g., Bayesian cumulative logistic regression)
Postnatal Phase: Infant linear growth velocity at 6 months
时间窗: Birth to 6 months
Infant linear growth velocity, calculated as: Length Velocity (cm/month) = Length at 6 months - Length at birth / Age in days / 30.4 Only infants exclusively/predominantly breastfed through 6 months will be included in this analysis. Method of Aggregation: Mean length velocity per intervention group Analysis Metric: Continuous variable; analysed using ANOVA or regression models with pairwise comparisons
次要结局
- Birth Weight (gm)(Within 72 hours of birth)
- Birth length (cm)(within 72 hours of birth)
- Gestational Weight Gain (GWG)(At birth)
- Intrauterine Growth Restriction (IUGR)(GA 20 and 32 weeks)
- Gestational age at birth(Within 72 hours of birth)
- Head circumference (cm)(within 72 hours of birth)
- Infant MUAC (cm)(within 72 hours of birth)
- Neonatal Mortality(within the first 28 days of life)
- Infant weight velocity(1, 2, 4, 6, 12, 24 months of life)
- Length-for-age z-score (LAZ)(2, 4, 6, 12, 24 months of life)
- Global Scale for Early Development (GSED) Assessment(6, 12 and 24 months of life)
- Weight-for-age z-score (WAZ)(2, 4, 6, 12, 24 months of life)
- Stunting, wasting and underweight Stunting <-2 LAZ ( Length for age Z) scores; Wasting <-2 WHZ (Weight for height Z) scores; underweight <-2WAZ (Weight for age Z) scores(2, 4, 6, 12, 24 months of life)
- Infant Brain Morphology and Volume (MRI Assessment Using Hyperfine Portable MRI)(6, 12 and 24 months of life)