Vaginal Progesterone for the Prevention of Preterm Birth in Women With Arrested Preterm Labor (PAL)

This study is currently recruiting participants.
Verified September 2013 by Washington University School of Medicine
Sponsor:
Collaborator:
Thrasher Research Fund
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01840228
First received: April 17, 2013
Last updated: September 11, 2013
Last verified: September 2013
  Purpose

Preterm birth, defined as birth before 37 weeks' gestation, is a leading cause of infant death and disease. Progesterone is the single most effective intervention in the prevention of preterm birth. However, current use of this therapy is limited to certain high-risk groups including women with a history of preterm birth and women with a short cervix. This study seeks to evaluate the efficacy of this preventive therapy in another high-risk group: women with arrested preterm labor. The investigators hypothesize that administration of vaginal progesterone in women who present with preterm labor but remain undelivered 12 hours after cessation of short-term therapy to inhibit contractions will result in lower rates of preterm birth before 37 weeks' than will administration of placebo.


Condition Intervention
Premature Birth
Obstetric Labor, Premature
Drug: Micronized progesterone suppository

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Vaginal Progesterone for the Prevention of Preterm Birth in Women With Arrested Preterm Labor

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Delivery before 37 weeks [ Time Frame: Duration of current pregnancy, anticipated maximum 18 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Delivery before 34 weeks [ Time Frame: Duration of current pregnancy, anticipated maximum 18 weeks ] [ Designated as safety issue: No ]
    Evaluated in women enrolled prior to 32 weeks gestation

  • Delivery within 2 weeks of randomization [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Number of days pregnancy prolongation [ Time Frame: Duration of current pregnancy, anticipated maximum 18 weeks ] [ Designated as safety issue: No ]
  • Infant birth weight [ Time Frame: Day of delivery in current pregnancy ] [ Designated as safety issue: No ]
  • Neonatal intensive care unit admission [ Time Frame: Followed for duration of neonatal hospital stay, estimated maximum 16 weeks ] [ Designated as safety issue: No ]
  • Chorioamnionitis [ Time Frame: Duration of current pregnancy, anticipated maximum 18 weeks ] [ Designated as safety issue: No ]
  • Composite neonatal outcome [ Time Frame: Followed for duration of neonatal hospital stay, estimated maximum 16 weeks ] [ Designated as safety issue: No ]
    A composite neonatal outcome comprising neonatal death, respiratory distress syndrome, bronchopulmonary dysplasia, severe (grade III/IV) interventricular hemorrhage, necrotizing enterocolitis, and sepsis.


Estimated Enrollment: 240
Study Start Date: May 2013
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Micronized progesterone suppository
Micronized progesterone suppository 200 mg vaginally daily until 36 6/7 weeks' gestation.
Drug: Micronized progesterone suppository
Placebo Comparator: Placebo suppository
One placebo suppository vaginally daily until 36 6/7 weeks' gestation.

Detailed Description:

RESEARCH DESIGN AND METHODS

The investigators will perform a randomized, blinded, placebo-controlled trial to evaluate the use of vaginal progesterone in women with arrested preterm labor after 24 weeks' gestation to reduce the risk of preterm birth before 37 weeks' gestation. Women enrolled in the study will be randomized to daily vaginal administration of progesterone (200 mg) or placebo from time of enrollment until 36 6/7 weeks' gestation. Women will be eligible if they have a singleton between 24 0/7 and 33 6/7 weeks' gestation and initially present with documented cervical change in the setting of regular uterine contraction but remain undelivered without further cervical change 12 hours after discontinuation of acute tocolytic therapy.

Randomization and Blinding- Participants in the study will be randomized using a computer-generated randomization scheme with 1:1 allocation to receive progesterone or placebo. Investigators and research team members, participants, and the obstetric providers will be blinded to the allocated intervention.

Procedures-

  • Data collection- Information will be recorded from the participant's medical record. Additional study information not included in the medical record will be obtained directly from the participant in an interview with the research team member.
  • Follow-up- Regardless of whether the participant remains hospitalized or is discharged prior to delivery, she will meet with a study coordinator every 2 weeks. During the follow-up visit, a study team member will discuss compliance with the study drug and possible side effects. The participant will fill out a 1-page questionnaire that asks questions about compliance and side effects. This information will be recorded and provided to the Data Safety and Monitoring Board at the midpoint review.

SAMPLE SIZE ESTIMATION

The investigators plan to enroll 240 patients, with a 1:1 allocation to treatment and placebo. This sample size is adequate to detect a one-third reduction in the primary outcome, delivery before 37 weeks and a 50% reduction in the rate of delivery within 2 weeks of randomization.

STATISTICAL ANALYSIS

Baseline characteristics of women randomized to progesterone will be compared with women randomized to placebo. Rates of delivery before 37 weeks' gestation will be compared among the groups using the Chi-square test. Secondary outcomes will be evaluated using the Chi-square test for binary outcomes and the Student t-test for continuous outcomes. Length of time from enrollment to delivery will be analyzed using Kaplan-Meier curves and the Cox proportional hazards model. All analyses will be performed using the intention-to-treat principle.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Singleton gestation
  • Estimated gestational age between 24 0/7 and 33 6/7 weeks' gestation
  • Initially present with regular contractions and the clinical diagnosis of preterm labor but remain undelivered without further cervical change 12 hours after discontinuation of acute tocolytic therapy
  • The participant's cervix must be at least 1 cm but less than 5 cm dilated at the time of enrollment

Exclusion Criteria:

  • Non-English speaking
  • Rupture of membranes
  • Chorioamnionitis
  • Non-reassuring fetal status
  • Maternal indication for delivery
  • Placental abruption
  • Intrauterine fetal demise
  • Prenatally diagnosed major fetal anomaly
  • Cervical cerclage in place
  • Previous administration of progesterone during the current pregnancy for a history of preterm birth or short cervix
  • Participant is either unwilling or unable to attend follow-up study visits following hospital discharge
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01840228

Contacts
Contact: Heather A Frey, MD 314-362-7300 freyh@wudosis.wustl.edu
Contact: Rachelle Busam, BSN, MFA 314-362-4664 buasmr@wudosis.wustl.edu

Locations
United States, Missouri
Washington University School of Medicine/ Barnes-Jewish Hospital Recruiting
St. Louis, Missouri, United States, 63110
Contact: Heather A Frey, MD    314-362-7300    freyh@wudosis.wustl.edu   
Contact: Rachelle Busam, BSN, MFA    314-362-4664    busamr@wudosis.wustl.edu   
Principal Investigator: Heather A Frey, MD         
Principal Investigator: George A Macones, MD, MSCE         
Principal Investigator: Alison G Cahill, MD, MSCI         
Sponsors and Collaborators
Washington University School of Medicine
Thrasher Research Fund
Investigators
Study Chair: George A Macones, MD, MSCE Washington University School of Medicine
  More Information

Publications:

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01840228     History of Changes
Other Study ID Numbers: 201301148
Study First Received: April 17, 2013
Last Updated: September 11, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:
Preterm
Progesterone

Additional relevant MeSH terms:
Obstetric Labor, Premature
Premature Birth
Obstetric Labor Complications
Pregnancy Complications
Progesterone
Progestins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014