Improving Pregnancy Outcomes With Progesterone (IPOP)

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

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

Study Overview

• Status: Completed
• Conditions: HIV-1-infection; Pre-term Birth
• Intervention / Treatment: Drug: 17P; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 800
• Phase: Phase 3

Contacts and Locations

Study Locations

• Zambia
  • Lusaka, Zambia
    • University Teaching Hospital
  • Lusaka, Zambia
    • Kamwala District Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 250 mg 17P; weekly intramuscular injection of 250mg 17P	Drug: 17P; Synthetic progestin; Other Names: 17-alpha hydroxyprogesterone caproate
PLACEBO_COMPARATOR: Placebo; weekly intramuscular injection of indistinguishable placebo	Other: Placebo; Non-active placebo comparator

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Bill and Melinda Gates Foundation; AMAG Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 7, 2018
• Primary Completion (ACTUAL): June 25, 2020
• Study Completion (ACTUAL): August 6, 2020

Study Registration Dates

• First Submitted: September 15, 2017
• First Submitted That Met QC Criteria: September 25, 2017
• First Posted (ACTUAL): September 29, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 22, 2021
• Last Update Submitted That Met QC Criteria: July 21, 2021
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: PreTerm Birth; HIV-1-infection; Antiretroviral Treatment
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Estrogen Antagonists; Progestins; 17 alpha-Hydroxyprogesterone Caproate; 11-hydroxyprogesterone
• Other Study ID Numbers: 17-1173; 1R01HD087119 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes