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Confirmatory Study of 17P vs Vehicle for Prevention of Preterm Birth in Women w/ Previous Spontaneous Preterm Delivery (PROLONG)

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ClinicalTrials.gov Identifier: NCT01004029
Recruitment Status : Completed
First Posted : October 29, 2009
Results First Posted : January 28, 2021
Last Update Posted : June 1, 2022
Sponsor:
Collaborator:
ResearchPoint Global
Information provided by (Responsible Party):
AMAG Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE October 27, 2009
First Posted Date  ICMJE October 29, 2009
Results First Submitted Date  ICMJE November 3, 2020
Results First Posted Date  ICMJE January 28, 2021
Last Update Posted Date June 1, 2022
Actual Study Start Date  ICMJE October 2009
Actual Primary Completion Date October 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 11, 2021)
  • Preterm Birth <35 Weeks Gestation [ Time Frame: Up to 35 weeks ]
    Determine if treatment with 17P reduces the rate of preterm birth < 35 weeks, 0 days of gestation in women with a previous singleton spontaneous preterm delivery.
  • Neonatal Composite Index (NCI) [ Time Frame: Until 28 days of life or discharge from the neonatal intensive care unit (NICU), whichever occurred later. ]
    The composite index is defined as a liveborn neonate with any of the following occurring at any time during the birth hospitalization up through discharge from the NICU: neonatal death, grade 3 or 4 intraventricular hemorrhage, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis or proven sepsis.
Original Primary Outcome Measures  ICMJE
 (submitted: October 28, 2009)
Determine if treatment with 17P reduces the rate of preterm birth < 35 weeks, 0 days of gestation in women with a singleton pregnancy, aged 18 years or older, with a previous singleton spontaneous preterm delivery. [ Time Frame: Delivery ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 11, 2021)
  • Fetal/Early Infant Death [ Time Frame: Delivery from 16 weeks 0 days through 19 weeks 6 days of gestation; or neonatal death occurring in liveborns born at less than 24 weeks gestation; or stillbirth (antepartum or intrapartum death) from 20 weeks gestation through term). ]
    Defined as spontaneous abortion/miscarriage (delivery from 16 weeks 0 days through 19 weeks 6 days of gestation) or neonatal death occurring in liveborns born at less than 24 weeks gestation or stillbirth (antepartum or intrapartum death from 20 weeks gestation through term), in the 17P group compared to the vehicle group
  • Preterm Birth Prior to 32 Weeks Gestation [ Time Frame: Up to 32 weeks ]
  • Preterm Birth Prior to 37 Weeks Gestation [ Time Frame: Up to 37 weeks ]
  • Stillbirths [ Time Frame: 20 weeks gestation until term ]
    Defined as all stillbirths/fetal deaths/in utero fetal losses occurring from 20 weeks gestation until term.
  • Neonatal Deaths With ≥24 Weeks Gestational Age [ Time Frame: Until 28 days of life or discharge from the NICU whichever occurred later. ]
    Neonatal death (from minutes after birth until 28 days of life) occurring in liveborns born at 24 weeks gestation or greater
Original Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2009)
Determine if 17P reduces the rate of neonatal mortality or morbidity, if and only if, the rate of preterm birth < 35 weeks, 0 days of gestation is statistically significant (i.e., hierarchical testing approach). [ Time Frame: Delivery ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Confirmatory Study of 17P vs Vehicle for Prevention of Preterm Birth in Women w/ Previous Spontaneous Preterm Delivery
Official Title  ICMJE A Phase 3B, Multi-Center, Randomized, Double-Blind Study of Hydroxyprogesterone Caproate (HPC) Injection, 250 mg/mL, Versus Vehicle for the Prevention of Preterm Birth in Women With a Previous Singleton Spontaneous Preterm Delivery
Brief Summary As part of the continuing effort to study the benefit and risks of 17P and preterm delivery, this study is designed as a multi-center, randomized, double-blind, vehicle-controlled clinical trial of 17P for the prevention of preterm birth prior to 35 weeks, 0 days of gestation in women with a singleton pregnancy, aged 18 years or older, with a previous singleton spontaneous preterm delivery. The study also includes a population pharmacokinetic (PK) substudy to assess the hydroxyprogesterone caproate (HPC) exposure-response relationship and the effect of body mass index (BMI) on the PK of 17P.
Detailed Description One of the most significant risk factors for preterm birth is previous pregnancy history. Women who have had a prior preterm birth have a 2.5-fold greater risk than women with no prior history of preterm birth. Prophylactic methods for prevention of preterm birth, including tocolytic drugs, bed rest, and other interventions such as cerclage, have been shown in most studies to be ineffective. One of the preventive measures that has shown effectiveness in randomized trials is the use of progesterone agents.9,10 Progesterone has been shown to support gestation and to inhibit uterine activity.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Preterm Birth
Intervention  ICMJE
  • Drug: Hydroxyprogesterone Caproate Injection (HPC), 250mg/mL
    1 mL intramuscular injection every week until 36 weeks, 6 days of gestation or delivery, whichever occurs first.
    Other Names:
    • Makena
    • 17P
  • Drug: Vehicle
    Weekly intramuscular injections of 1 mL vehicle inert oil until 36 weeks, 6 days of gestation or delivery, whichever occurs first.
    Other Name: Placebo
Study Arms  ICMJE
  • Placebo Comparator: Vehicle
    Castor Oil
    Intervention: Drug: Vehicle
  • Active Comparator: Hydroxyprogesterone Caproate Injection (HPC), 250 mg/mL
    HPC 250 mg/mL in oil
    Intervention: Drug: Hydroxyprogesterone Caproate Injection (HPC), 250mg/mL
Publications * Blackwell SC, Gyamfi-Bannerman C, Biggio JR Jr, Chauhan SP, Hughes BL, Louis JM, Manuck TA, Miller HS, Das AF, Saade GR, Nielsen P, Baker J, Yuzko OM, Reznichenko GI, Reznichenko NY, Pekarev O, Tatarova N, Gudeman J, Birch R, Jozwiakowski MJ, Duncan M, Williams L, Krop J. 17-OHPC to Prevent Recurrent Preterm Birth in Singleton Gestations (PROLONG Study): A Multicenter, International, Randomized Double-Blind Trial. Am J Perinatol. 2020 Jan;37(2):127-136. doi: 10.1055/s-0039-3400227. Epub 2019 Oct 25.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 11, 2021)
1740
Original Estimated Enrollment  ICMJE
 (submitted: October 28, 2009)
1707
Actual Study Completion Date  ICMJE October 2018
Actual Primary Completion Date October 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Each subject must meet the following criteria to be enrolled in this study:

  1. Age ≥ 18 years.
  2. Singleton gestation.
  3. Project gestational age 16 weeks 0 days of gestation or more and less than or equal to 20 weeks 6 days of gestation at the time of randomization, based on clinical information and evaluation of the first ultrasound.
  4. Documented history of a previous singleton spontaneous preterm delivery. Spontaneous preterm birth is defined as delivery from 20 weeks 0 days to 36 weeks 6 days of gestation following spontaneous preterm labor or pPROM. Where possible, the gestational age of the previous preterm birth (referred to as the qualifying delivery) should be determined as described in "Gestational Age Determination". If the gestational age at delivery is obtained directly from the medical record and more than one gestational age appears, the latest will be used. As a validation of the gestational age of the previous delivery, if the infant weighed more than 3300 grams (the birth weight 90th percentile for 36 weeks gestational age), this will not qualify as preterm. The previous preterm delivery cannot be an antepartum stillbirth.

Exclusion Criteria:

  1. Multifetal gestation.
  2. Known major fetal anomaly or fetal demise. An ultrasound examination between 14 weeks 0 days through 20 weeks 3 days of gestation must be performed to rule out fetal anomalies.
  3. Progesterone treatment in any form (i.e., vaginal, oral, intramuscular) during current pregnancy, other than micronized progesterone delivered orally or vaginally provided it is stopped at least 4 weeks prior to the first dose of study medication.
  4. Heparin therapy during current pregnancy or history of thromboembolic disease.
  5. Maternal medical/obstetrical complications including:

    • Current or planned cerclage
    • Hypertension requiring medication
    • Seizure disorder
  6. Subjects with a uterine anomaly (uterine didelphys or bicornate uterus). However, subjects with uterine fibroids are eligible for the study.
  7. Unwillingness to comply with and complete the study.
  8. A 14 weeks 0 days through 20 weeks 3 days of gestation ultrasound cannot be arranged before randomization.
  9. Participation in an antenatal study in which the clinical status or intervention may influence gestational age at delivery.
  10. Participation in this trial in a previous pregnancy. Women who were screened in a previous pregnancy, but not randomized, do not have to be excluded.
  11. Known hypersensitivity to hydroxyprogesterone caproate or its components.
  12. Have any significant medical disorder that, in the opinion of the investigator, would be a contraindication to the use of the drug including those listed in section 5.3.2 of the investigational brochure. Other examples to consider include uncontrolled diabetes, known HIV infection or renal dysfunction.
  13. Have any significant medical disorder that, in the opinion of the investigator, would preclude accurate evaluation of the subject's condition or outcome in the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Bulgaria,   Canada,   Czechia,   Hungary,   Italy,   Russian Federation,   Spain,   Ukraine,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01004029
Other Study ID Numbers  ICMJE 17P-ES-003
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party AMAG Pharmaceuticals, Inc.
Original Responsible Party Robb Hesley, Vice President Business Development, Hologic, Inc.
Current Study Sponsor  ICMJE AMAG Pharmaceuticals, Inc.
Original Study Sponsor  ICMJE Hologic, Inc.
Collaborators  ICMJE ResearchPoint Global
Investigators  ICMJE Not Provided
PRS Account AMAG Pharmaceuticals, Inc.
Verification Date May 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP