search
Back to results

Calcium Aspirin Multiple Micronutrients (CAMMS) to Reduce Preterm Birth (CAMMS)

Primary Purpose

Preterm Labor, Small for Gestational Age at Delivery, Hypertensive Disorder of Pregnancy

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Calcium aspirin multiple micronutrients
Iron-folic Acid
Sponsored by
Johns Hopkins Bloomberg School of Public Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Preterm Labor

Eligibility Criteria

15 Years - undefined (Child, Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Woman, confirmed pregnant by urinary pregnancy test 6<20 weeks' gestation determined by fetal ultrasound exam; Pregnancy must be intrauterine; multiple fetus pregnancies are eligible. Women must be willing and able to give informed consent; willing to receive antenatal visits at one of the study clinics. In Burkina Faso, women must be willing to take monthly sulfadoxine-pyrimethamine. Exclusion Criteria: Pregnant women who are currently taking aspirin, calcium, or MMS; have a history of peptic ulcer or have any other contraindications to any of the study drugs; have acute or chronic condition that might interfere with the study as judged by the research clinician including severe anemia defined as Hb<5 g/dL; have other reasons which, at the study research physician's discretion, mean that receipt of the study drugs or participation in the trial would not be advisable. NOTE: Women who have been started on IFA by MoH or private health care provider but are willing discontinue the IFA dispensed by MoH and to be randomized to IFA or CAMMS will not be excluded.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Calcium aspirin multiple micronutrients

    Iron folic acid

    Arm Description

    500 mg elemental calcium (as 1250 mg calcium carbonate) 81 mg aspirin 1 tablet United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP) formula, which is a Multiple Micronutrient Supplement (MMS) for pregnant women

    60 mg iron + 400 μg folic acid given as a combined tablet

    Outcomes

    Primary Outcome Measures

    Total preterm birth
    Gestational age at birth < 37 weeks, stratified by spontaneous and indicated.

    Secondary Outcome Measures

    Total very early preterm birth
    gestational age at birth ≥20 and <28 weeks, stratified by spontaneous and indicated.
    Total early preterm birth
    gestational age ≥28 and <34 weeks, stratified by spontaneous and indicated.
    Low birth weight
    <2500 g
    Very low birth weigh
    <1500 g
    Small for gestational age
    <10th percentile weight for gestational age using INTERGROWTH 21st Reference standards
    Stillbirth
    fetal loss > 20 gestational weeks
    Neonatal death
    death of a live-born infant <28 completed days of life
    Miscarriage
    fetal loss <20 gestational weeks
    Live-or-stillbirth-preterm-deliveries
    stillbirths delivered <37 weeks' gestation + preterm births
    Hypertensive disorder of pregnancy
    Maternal Systolic BP>140 and/or Diastolic BP>90 between enrollment and 42 days postpartum
    Maternal anemia
    Hb<110 g/L during the third trimester of pregnancy
    Maternal death
    death of a woman between enrollment at 6<20 weeks gestation and 42 days postpartum
    Perinatal mortality
    Stillbirths + neonatal deaths
    Birth weight
    infant weight (g) ≤ 72 h of birth
    Gestational age at birth
    Completed days of gestation at birth
    Weight-for-gestational-age-Z-score at birth
    WAZ, using INTERGROWTH 21st Reference standards

    Full Information

    First Posted
    November 3, 2022
    Last Updated
    October 12, 2023
    Sponsor
    Johns Hopkins Bloomberg School of Public Health
    Collaborators
    Aga Khan University, Institut Africain de Santé Publique (IASP), Ouagadougou, Burkina Faso, Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe, Cristiana Health Care, Newark, DE, Columbia University
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT05612984
    Brief Title
    Calcium Aspirin Multiple Micronutrients (CAMMS) to Reduce Preterm Birth
    Acronym
    CAMMS
    Official Title
    Calcium Aspirin Multiple Micronutrients (CAMMS) or Iron-folic Acid (IFA) to Reduce Preterm Birth
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    April 1, 2024 (Anticipated)
    Primary Completion Date
    June 30, 2026 (Anticipated)
    Study Completion Date
    December 31, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Johns Hopkins Bloomberg School of Public Health
    Collaborators
    Aga Khan University, Institut Africain de Santé Publique (IASP), Ouagadougou, Burkina Faso, Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe, Cristiana Health Care, Newark, DE, Columbia University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This trial will evaluate the impact of an integrated intervention of daily maternal calcium, aspirin, and multiple micronutrients (CAMMS) compared to iron-folic acid (IFA) during pregnancy on preterm birth and other adverse birth outcomes. Both interventions will be delivered through existing antenatal service platforms using context-specific strategies informed by formative research incorporating human-centered design processes to achieve high acceptability and high adherence, in three low-income countries with diverse contexts: Burkina Faso, Pakistan, and Zimbabwe.
    Detailed Description
    The CAMMS trial is an individually randomized, unblinded, phase III trial comparing aspirin, calcium and multiple micronutrients (intervention) versus iron-folic acid (control) among 10,000 pregnant women. The primary outcome is total preterm birth, stratified by spontaneous and indicated. Eligible pregnant women will be enrolled from antenatal clinics in three study populations in Burkina Faso, Pakistan, and Zimbabwe following written informed consent. All women attending antenatal care (ANC) who are positive on a urine pregnancy test and have a fetal ultrasound examination confirming fetal heartbeat, intrauterine pregnancy, and gestational age 6<20 weeks' will be eligible for enrollment. Women who are <6 weeks will be rescheduled for 2-3 weeks later. Baseline data and clinical assessments will be conducted, and women will be randomized to daily ingestion of CAMMS or IFA until delivery. In Burkina Faso, for women randomized to CAMMS, the aspirin will be withheld until 13 weeks' gestation when it can be initiated concurrently with sulfadoxine-pyrimethamine. Women will receive context-specific adherence promotion interventions designed during formative research incorporating Human-Centered Design (HCD) processes in each country. Mothers will be followed up at 4-weekly intervals throughout pregnancy plus an additional study contact (by visit, phone call, WhatsApp, or text message) at 1-2 weeks after starting the study drug to check for tolerance and adherence. Women may also be seen at closer intervals in the third trimester by the Ministry of Health clinics. Women will be encouraged to deliver in a health institution. Between baseline and delivery, research procedures will be undertaken by research staff based at antenatal clinics during mothers' routine antenatal visits to reduce time burden on participants. Depending on gestational age at recruitment, women will receive 7-11 research visits. One additional visit or contact by text-message (SMS) or phone call will occur one-two weeks after randomization to check that the women is tolerating and correctly taking the interventions. At delivery, infant weight and gestational age will be measured/determined by research staff based at delivery clinics or, for home deliveries, during home visits conducted within 72 hours of delivery. For infants born outside the study area or who are not reached by research staff within 72 hours, date of birth and birth weight will be transcribed from the infant's health record with source of information noted. In unusual situations where the mother and infant cannot be reached in person before 180 days postpartum but can be reached by telephone, WhatsApp, or Text message, maternal report of data of birth and birth weight will be recorded with the source of information noted. For all infants reached by a research staff member within 72 hours of birth, birth length and head circumference will be measured by standardized research staff with high quality equipment (length measured to nearest 0.1cm with infant length board and Shorr insert-tape (Weigh & Measure LLC., Olney, MD, USA). Mothers and infants will be followed to 42 days post-partum for vital status and post-partum maternal Adverse Events (AEs) and Serious Adverse Events (SAEs). This visit may be conducted in person, by telephone, WhatsApp or text message with the source of information recorded.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Preterm Labor, Small for Gestational Age at Delivery, Hypertensive Disorder of Pregnancy, Low Birth Weight, Neonatal Death

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Model Description
    Pregnant women will be individually randomized to daily CAMMS or IFA from recruitment (at 6<20 weeks gestation) to delivery.
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    10000 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Calcium aspirin multiple micronutrients
    Arm Type
    Experimental
    Arm Description
    500 mg elemental calcium (as 1250 mg calcium carbonate) 81 mg aspirin 1 tablet United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP) formula, which is a Multiple Micronutrient Supplement (MMS) for pregnant women
    Arm Title
    Iron folic acid
    Arm Type
    Active Comparator
    Arm Description
    60 mg iron + 400 μg folic acid given as a combined tablet
    Intervention Type
    Combination Product
    Intervention Name(s)
    Calcium aspirin multiple micronutrients
    Other Intervention Name(s)
    CAMMS
    Intervention Description
    Women randomized to CAMMS will receive weekly blister cards containing all 3 components: 1 81 mg aspirin tablet, 1 UNIMMAP MMS, and 1 500-mg elemental calcium tablets. Blister packages will be labeled with times of day and days of week when tablets are to be taken. 4 weekly blister cards will be packaged in one unit box.
    Intervention Type
    Dietary Supplement
    Intervention Name(s)
    Iron-folic Acid
    Other Intervention Name(s)
    IFA
    Intervention Description
    Women randomized to IFA will receive monthly (28-day) blister cards containing containing 1 combined IFA tablet to be taken each day. 1 4-weekly blister card will be packaged in one unit box.
    Primary Outcome Measure Information:
    Title
    Total preterm birth
    Description
    Gestational age at birth < 37 weeks, stratified by spontaneous and indicated.
    Time Frame
    At birth
    Secondary Outcome Measure Information:
    Title
    Total very early preterm birth
    Description
    gestational age at birth ≥20 and <28 weeks, stratified by spontaneous and indicated.
    Time Frame
    At birth
    Title
    Total early preterm birth
    Description
    gestational age ≥28 and <34 weeks, stratified by spontaneous and indicated.
    Time Frame
    At birth
    Title
    Low birth weight
    Description
    <2500 g
    Time Frame
    At birth
    Title
    Very low birth weigh
    Description
    <1500 g
    Time Frame
    At birth
    Title
    Small for gestational age
    Description
    <10th percentile weight for gestational age using INTERGROWTH 21st Reference standards
    Time Frame
    At birth
    Title
    Stillbirth
    Description
    fetal loss > 20 gestational weeks
    Time Frame
    Day of fetal loss from > 20 weeks gestation to birth
    Title
    Neonatal death
    Description
    death of a live-born infant <28 completed days of life
    Time Frame
    Day of death, between birth and <28 completed days of life
    Title
    Miscarriage
    Description
    fetal loss <20 gestational weeks
    Time Frame
    Day of fetal loss, up to < 20 weeks gestation
    Title
    Live-or-stillbirth-preterm-deliveries
    Description
    stillbirths delivered <37 weeks' gestation + preterm births
    Time Frame
    Day of fetal loss or birth, up to < 37 weeks gestation
    Title
    Hypertensive disorder of pregnancy
    Description
    Maternal Systolic BP>140 and/or Diastolic BP>90 between enrollment and 42 days postpartum
    Time Frame
    From enrollment at 6<20 weeks gestation through 42 days postpartum
    Title
    Maternal anemia
    Description
    Hb<110 g/L during the third trimester of pregnancy
    Time Frame
    30 weeks' gestation
    Title
    Maternal death
    Description
    death of a woman between enrollment at 6<20 weeks gestation and 42 days postpartum
    Time Frame
    day of woman's death between enrollment at 6<20 weeks gestation up to 42 days postpartum
    Title
    Perinatal mortality
    Description
    Stillbirths + neonatal deaths
    Time Frame
    fetal loss or infant death <28 days of completed life
    Title
    Birth weight
    Description
    infant weight (g) ≤ 72 h of birth
    Time Frame
    At birth
    Title
    Gestational age at birth
    Description
    Completed days of gestation at birth
    Time Frame
    At birth
    Title
    Weight-for-gestational-age-Z-score at birth
    Description
    WAZ, using INTERGROWTH 21st Reference standards
    Time Frame
    At birth
    Other Pre-specified Outcome Measures:
    Title
    Infant birth length and birth head circumference
    Description
    Among infants assessed <72 hours after birth by research staff
    Time Frame
    birth
    Title
    Tolerance of CAMMS compared to IFA
    Description
    Rates of Grade 1 or 2 nausea, vomiting, rash/hives, diarrhea, constipation, and vaginal bleeding from initiation of the interventions through 42 days post-partum
    Time Frame
    Up to 42 days post-partum
    Title
    Safety of CAMMS compared to IFA
    Description
    Rates of SAEs, Grade 3 or 4 nausea, vomiting, rash/hives, diarrhea, constipation, and vaginal bleeding, stratified by relatedness to the intervention from initiation of the interventions through 42 days post-partum
    Time Frame
    Up to 42 days post-partum

    10. Eligibility

    Sex
    Female
    Minimum Age & Unit of Time
    15 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Woman, confirmed pregnant by urinary pregnancy test 6<20 weeks' gestation determined by fetal ultrasound exam; Pregnancy must be intrauterine; multiple fetus pregnancies are eligible. Women must be willing and able to give informed consent; willing to receive antenatal visits at one of the study clinics. In Burkina Faso, women must be willing to take monthly sulfadoxine-pyrimethamine. Exclusion Criteria: Pregnant women who are currently taking aspirin, calcium, or MMS; have a history of peptic ulcer or have any other contraindications to any of the study drugs; have acute or chronic condition that might interfere with the study as judged by the research clinician including severe anemia defined as Hb<5 g/dL; have other reasons which, at the study research physician's discretion, mean that receipt of the study drugs or participation in the trial would not be advisable. NOTE: Women who have been started on IFA by MoH or private health care provider but are willing discontinue the IFA dispensed by MoH and to be randomized to IFA or CAMMS will not be excluded.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Jean H Humphrey, ScD
    Phone
    443-540-8836
    Email
    jhumphr2@jhu.edu
    First Name & Middle Initial & Last Name or Official Title & Degree
    Monica M Pasqualino, PhD
    Email
    mpasqua2@jhmi.edu

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    We will deposit anonymized data in an existing repository after publication of the primary and key secondary findings. (
    IPD Sharing Time Frame
    About 2 years after the end of the trial when primary and secondary outcomes have been reported in the peer reviewed literature.

    Learn more about this trial

    Calcium Aspirin Multiple Micronutrients (CAMMS) to Reduce Preterm Birth

    We'll reach out to this number within 24 hrs