Improving Pregnancy Outcomes With Progesterone

Study Overview
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Brief Summary
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This is a phase III, double-masked, placebo-controlled, randomized controlled trial taking place in Zambia.

Detailed Description
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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.

Official Title
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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

Conditions
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Pre-term Birth, HIV-1-infection

Intervention / Treatment
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* Drug: 17P
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase III, double-masked, placebo-controlled, randomized controlled trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 250 mg 17P<br>weekly intramuscular injection of 250mg 17P | Drug: 17P<br>* Synthetic progestin<br>* Other names: 17-alpha hydroxyprogesterone caproate;|
| Placebo Comparator: Placebo<br>weekly intramuscular injection of indistinguishable placebo | Other: Placebo<br>* Non-active placebo comparator<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Preterm Birth <37 Weeks | Delivery prior to 37 gestational weeks | At delivery, up to 37 weeks of gestation | 
| Number of Participants Experiencing Preterm Birth <34 Weeks | Delivery prior to 34 gestational weeks | At delivery, up to 34 weeks of gestation | 
| Number of Participants Experiencing Preterm Birth <28 Weeks | Delivery prior to 28 gestational weeks | At delivery, up to 28 weeks of gestation | 
| Number of Participants Experiencing Stillbirth | Participants who had a fetus born without signs of life at any gestational age | At delivery, up to approximately 40 weeks of gestation | 
| Number of Participants Experiencing Spontaneous Delivery <37 Weeks | Delivery prior to 37 weeks of gestation that was initiated spontaneously, without provider intervention | At delivery, up to 37 weeks of gestation | 
| Number of Participants Experiencing Spontaneous Delivery <34 Weeks | Delivery prior to 34 weeks of gestation that was initiated spontaneously, without provider intervention | At delivery, up to 34 weeks of gestation | 
| Number of Participants Experiencing Spontaneous Delivery <28 Weeks | Delivery prior to 28 weeks of gestation that was initiated spontaneously, without provider intervention | At delivery, up to 28 weeks of gestation | 
| Number of Infants With Birth Weight <10th Percentile for Gestational Age | Infant born with a weight below the 10th percentile for gestational age | Birth | 
| Number of Infants With Birth Weight <3rd Percentile for Gestational Age | Infant born with a weight below the 3rd percentile for gestational age | Birth | 
| Number of Infants Who Experienced Maternal-to-Child HIV Transmission | Confirmed HIV infection in an infant | At 6 weeks of life | 
| Number of Neonatal Deaths | Death of an infant following live birth | Birth through 28 days postpartum | 
| Number of Infants With 1-minute Apgar Score <7 | 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. | 1 minute of life | 
| Number of Infants With 5-minute Apgar Score <7 | 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. | 5 minutes of life | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PreTerm Birth, HIV-1-infection, Antiretroviral Treatment