Clinical trial NCT03297216: Improving Pregnancy Outcomes With Progesterone
Official title: Z 31702 - Improving Pregnancy Outcomes With Progesterone (IPOP): a Trial of 17-Hydroxyprogesterone Caproate to Reduce Preterm Birth Among Women Receiving Antiretroviral Therapy in Pregnancy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pre-term Birth
HIV-1-infection
Keywords: PreTerm Birth
HIV-1-infection
Antiretroviral Treatment
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: AMAG Pharmaceuticals, Inc.
name: Bill and Melinda Gates Foundation
First posted: 2017-09-29
Enrollment: 800
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase III, double-masked, placebo-controlled, randomized controlled trial
Primary purpose: PREVENTION

Brief summary: This is a phase III, double-masked, placebo-controlled, randomized controlled trial taking place in Zambia.

Detailed description: Weekly intramuscular injections of 250mg 17-alpha hydroxyprogesterone caproate (17P) or indistinguishable placebo will be randomly allocated in a 1:1 ratio started between 16-24 weeks gestation and administered weekly thereafter until 36 6/7 gestational weeks, stillbirth, or delivery, whichever is sooner.

Individual participants will be followed from enrollment (prior to 24 weeks gestation) through 42 days postpartum.

Eligibility criteria: Inclusion Criteria:

* 18 years of age or older
* less than 24 0/7 weeks of gestation
* viable intrauterine singleton pregnancy confirmed by ultrasound
* antibody-confirmed HIV-1 infection
* currently receiving antiretroviral l therapy (ART) or intending to commence ART in pregnancy
* ability and willingness to provide written informed consent
* intent to remain in current geographical area of residence for the duration of study
* willing to adhere to weekly study visit schedule

Exclusion Criteria:

* confirmed prior spontaneous preterm birth
* multiple gestation
* known uterine anomaly
* planned or in situ cervical cerclage
* major fetal anomaly detected on screening ultrasound
* indication for planned delivery prior to 37 weeks (e.g., prior classical cesarean)
* threatened abortion, preterm labor, or ruptured membranes at time of enrollment
* known allergy or medical comorbidity listed as a contraindication to 17P in the prescribing information
* prior participation in the trial
* any other condition (social or medical) which, in the opinion of the study staff, would make trial participation unsafe or complicate data interpretation.

Primary outcomes:
measure: Number of Participants Experiencing Preterm Births or Stillbirths
timeFrame: At delivery, up to 37 weeks of gestation for live births and up to approximately 40 weeks of gestation for stillbirths
Secondary outcomes:
measure: Number of Participants Experiencing Preterm Birth <37 Weeks
timeFrame: At delivery, up to 37 weeks of gestation
measure: Number of Participants Experiencing Preterm Birth <34 Weeks
timeFrame: At delivery, up to 34 weeks of gestation
measure: Number of Participants Experiencing Preterm Birth <28 Weeks
timeFrame: At delivery, up to 28 weeks of gestation
measure: Number of Participants Experiencing Stillbirth
timeFrame: At delivery, up to approximately 40 weeks of gestation
measure: Number of Participants Experiencing Spontaneous Delivery <37 Weeks
timeFrame: At delivery, up to 37 weeks of gestation
measure: Number of Participants Experiencing Spontaneous Delivery <34 Weeks
timeFrame: At delivery, up to 34 weeks of gestation
measure: Number of Participants Experiencing Spontaneous Delivery <28 Weeks
timeFrame: At delivery, up to 28 weeks of gestation
measure: Number of Infants With Birth Weight <10th Percentile for Gestational Age
timeFrame: Birth
measure: Number of Infants With Birth Weight <3rd Percentile for Gestational Age
timeFrame: Birth
measure: Number of Infants Who Experienced Maternal-to-Child HIV Transmission
timeFrame: At 6 weeks of life
measure: Number of Neonatal Deaths
timeFrame: Birth through 28 days postpartum
measure: Number of Infants With 1-minute Apgar Score <7
timeFrame: 1 minute of life
measure: Number of Infants With 5-minute Apgar Score <7
timeFrame: 5 minutes of life
Other outcomes:
Locations:
city: Lusaka
country: Zambia
facility: Kamwala District Clinic
city: Lusaka
country: Zambia
facility: University Teaching Hospital
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Jeff Stringer, MD, FACOG
role: PRINCIPAL_INVESTIGATOR
References:
citation: Price JT, Vwalika B, Freeman BL, Cole SR, Saha PT, Mbewe FM, Phiri WM, Peterson M, Muyangwa D, Sindano N, Mwape H, Smithmyer ME, Kasaro MP, Rouse DJ, Goldenberg RL, Chomba E, Stringer JSA. Weekly 17 alpha-hydroxyprogesterone caproate to prevent preterm birth among women living with HIV: a randomised, double-blind, placebo-controlled trial. Lancet HIV. 2021 Oct;8(10):e605-e613. doi: 10.1016/S2352-3018(21)00150-8. Epub 2021 Sep 9.
citation: Price JT, Vwalika B, Freeman BL, Cole SR, Mulenga HB, Winston J, Mbewe FM, Chomba E, Mofenson LM, Rouse DJ, Goldenberg RL, Stringer JSA. Intramuscular 17-hydroxyprogesterone caproate to prevent preterm birth among HIV-infected women in Zambia: study protocol of the IPOP randomized trial. BMC Pregnancy Childbirth. 2019 Feb 27;19(1):81. doi: 10.1186/s12884-019-2224-8.