Calcium Aspirin Multiple Micronutrients (CAMMS) to Reduce Preterm Birth

Preterm Labor Clinical Trial

— CAMMS  

Official title:

Calcium Aspirin Multiple Micronutrients (CAMMS) or Iron-folic Acid (IFA) to Reduce Preterm Birth

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05612984
• Other study ID #: INV-036663
• Status: Withdrawn
• Phase: Phase 3
• Start date: April 1, 2024
• Est. completion date: December 31, 2026

Study information

• Verified date: April 2024
• Source: Johns Hopkins Bloomberg School of Public Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 31, 2026
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 15 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Birth Weight
• Hypertension
• Hypertensive Disorder of Pregnancy
• Low Birth Weight
• Neonatal Death
• Obstetric Labor, Premature
• Perinatal Death
• Premature Birth
• Preterm Labor
• Small for Gestational Age at Delivery
• Toxemia

Intervention

Combination Product:
• Calcium aspirin multiple micronutrients
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.

Dietary Supplement:
• Iron-folic Acid
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.

Locations

Country	Name	City	State
n/a

Sponsors (6)

Lead Sponsor	Collaborator
Johns Hopkins Bloomberg School of Public Health	Aga Khan University, Christiana Care Health Services, Columbia University, Institut Africain de Sante Publique, Zvitambo Institute for Maternal and Child Health Research

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Infant birth length and birth head circumference	Among infants assessed <72 hours after birth by research staff	birth
Other	Tolerance of CAMMS compared to IFA	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	Up to 42 days post-partum
Other	Safety of CAMMS compared to IFA	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	Up to 42 days post-partum
Primary	Total preterm birth	Gestational age at birth < 37 weeks, stratified by spontaneous and indicated.	At birth
Secondary	Total very early preterm birth	gestational age at birth =20 and <28 weeks, stratified by spontaneous and indicated.	At birth
Secondary	Total early preterm birth	gestational age =28 and <34 weeks, stratified by spontaneous and indicated.	At birth
Secondary	Low birth weight	<2500 g	At birth
Secondary	Very low birth weigh	<1500 g	At birth
Secondary	Small for gestational age	<10th percentile weight for gestational age using INTERGROWTH 21st Reference standards	At birth
Secondary	Stillbirth	fetal loss > 20 gestational weeks	Day of fetal loss from > 20 weeks gestation to birth
Secondary	Neonatal death	death of a live-born infant <28 completed days of life	Day of death, between birth and <28 completed days of life
Secondary	Miscarriage	fetal loss <20 gestational weeks	Day of fetal loss, up to < 20 weeks gestation
Secondary	Live-or-stillbirth-preterm-deliveries	stillbirths delivered <37 weeks' gestation + preterm births	Day of fetal loss or birth, up to < 37 weeks gestation
Secondary	Hypertensive disorder of pregnancy	Maternal Systolic BP>140 and/or Diastolic BP>90 between enrollment and 42 days postpartum	From enrollment at 6<20 weeks gestation through 42 days postpartum
Secondary	Maternal anemia	Hb<110 g/L during the third trimester of pregnancy	30 weeks' gestation
Secondary	Maternal death	death of a woman between enrollment at 6<20 weeks gestation and 42 days postpartum	day of woman's death between enrollment at 6<20 weeks gestation up to 42 days postpartum
Secondary	Perinatal mortality	Stillbirths + neonatal deaths	fetal loss or infant death <28 days of completed life
Secondary	Birth weight	infant weight (g) = 72 h of birth	At birth
Secondary	Gestational age at birth	Completed days of gestation at birth	At birth
Secondary	Weight-for-gestational-age-Z-score at birth	WAZ, using INTERGROWTH 21st Reference standards	At birth