Improving Pregnancy Outcomes With Progesterone

Phase 3

Completed

Conditions: HIV-1-infection
Pre-term Birth

Interventions: Drug: 17P
Other: Placebo

Registration Number: NCT03297216

Lead Sponsor: University of North Carolina, Chapel Hill

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 800

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
250 mg 17P	17P	weekly intramuscular injection of 250mg 17P
Placebo	Placebo	weekly intramuscular injection of indistinguishable placebo

Primary Outcome Measures

Name	Time	Method
Number of Participants Experiencing Preterm Births or Stillbirths	At delivery, up to 37 weeks of gestation for live births and up to approximately 40 weeks of gestation for stillbirths	A composite of live births prior to 37 weeks of gestation or stillbirth occurring at any gestational age

Secondary Outcome Measures

Name	Time	Method
Number of Participants Experiencing Spontaneous Delivery <28 Weeks	At delivery, up to 28 weeks of gestation	Delivery prior to 28 weeks of gestation that was initiated spontaneously, without provider intervention
Number of Neonatal Deaths	Birth through 28 days postpartum	Death of an infant following live birth
Number of Participants Experiencing Spontaneous Delivery <34 Weeks	At delivery, up to 34 weeks of gestation	Delivery prior to 34 weeks of gestation that was initiated spontaneously, without provider intervention
Number of Participants Experiencing Preterm Birth <34 Weeks	At delivery, up to 34 weeks of gestation	Delivery prior to 34 gestational weeks
Number of Infants With Birth Weight <3rd Percentile for Gestational Age	Birth	Infant born with a weight below the 3rd percentile for gestational age
Number of Infants Who Experienced Maternal-to-Child HIV Transmission	At 6 weeks of life	Confirmed HIV infection in an infant
Number of Participants Experiencing Spontaneous Delivery <37 Weeks	At delivery, up to 37 weeks of gestation	Delivery prior to 37 weeks of gestation that was initiated spontaneously, without provider intervention
Number of Infants With 1-minute Apgar Score <7	1 minute of life	Apgar score of less than 7 at 1 minute of life. Apgar stands for "Appearance, Pulse, Grimace, Activity, and Respiration" and is a quick test rated on a scale of 1-10 performed on a baby at one minute of life to determine how well the baby tolerated the birth process. Scores 7 and above are generally normal, 4 to 6 fairly low, and 3 and below are generally regarded as critically low.
Number of Participants Experiencing Preterm Birth <37 Weeks	At delivery, up to 37 weeks of gestation	Delivery prior to 37 gestational weeks
Number of Participants Experiencing Preterm Birth <28 Weeks	At delivery, up to 28 weeks of gestation	Delivery prior to 28 gestational weeks
Number of Participants Experiencing Stillbirth	At delivery, up to approximately 40 weeks of gestation	Participants who had a fetus born without signs of life at any gestational age
Number of Infants With Birth Weight <10th Percentile for Gestational Age	Birth	Infant born with a weight below the 10th percentile for gestational age
Number of Infants With 5-minute Apgar Score <7	5 minutes of life	Apgar score of less than 7 at 5 minutes of life. Apgar stands for "Appearance, Pulse, Grimace, Activity, and Respiration" and is a quick test rated on a scale of 1-10 performed on a baby at five minutes of life to assess how well the baby is doing following delivery. Scores 7 and above are generally normal, 4 to 6 fairly low, and 3 and below are generally regarded as critically low.