Vaginal Progesterone for the Prevention of Preterm Birth in Women With Arrested Preterm Labor
Information source: Washington University School of Medicine
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Premature Birth; Obstetric Labor, Premature
Intervention: Micronized progesterone suppository (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: Washington University School of Medicine Official(s) and/or principal investigator(s): George A Macones, MD, MSCE, Study Chair, Affiliation: Washington University School of Medicine
Overall contact: Molly J Stout, MD, MSCI, Phone: 314-362-8895, Email: stoutm@wudosis.wustl.edu
Summary
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.
Clinical Details
Official title: Vaginal Progesterone for the Prevention of Preterm Birth in Women With Arrested Preterm Labor
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Primary outcome: Delivery before 37 weeks
Secondary outcome: Delivery before 34 weeksDelivery within 2 weeks of randomization Number of days pregnancy prolongation Infant birth weight Neonatal intensive care unit admission Chorioamnionitis Composite neonatal outcome
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 or twin gestation between 24 0/7 and 33 6/7 weeks' gestation and
initially present with regular uterine contractions and a clinical diagnosis of preterm
labor but remain undelivered without further cervical change 12 hours after discontinuation
of acute tocolytic therapy. Women may also participate if it has been less than if they are
considered eligible for discharge based on attending physician judgement prior to the 12
hour period of time.
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 120 patients, with a 1: 1 allocation to treatment and
placebo. This sample size is adequate to detect a one-half reduction in the primary outcome,
delivery before 37 weeks.
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
Minimum age: 18 Years.
Maximum age: 50 Years.
Gender(s): Female.
Criteria:
Inclusion Criteria:
- Singleton of twin gestation
- Estimated gestational age between 24 0/7 and 33 6/7 weeks' gestation
- Initially present with regular contractions and clinical diagnosis of preterm labor
but remain undelivered with 1) no further cervical change 12 hours after
discontinuation of acute tocolytic therapy; or 2) be considered eligible for
discharge based on attending physician judgment prior to the 12 hour period of time
- The participant's cervix must be at least 1 cm 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
Locations and Contacts
Molly J Stout, MD, MSCI, Phone: 314-362-8895, Email: stoutm@wudosis.wustl.edu
Washington University School of Medicine/ Barnes-Jewish Hospital, St. Louis, Missouri 63110, United States; Recruiting Molly J Stout, MD, MSCI, Phone: 314-362-8895, Email: stoutm@wudosis.wustl.edu Monica Anderson, RN, BSN, Phone: 314-747-1390, Email: andersonm@wudosis.wustl.edu Heather A Frey, MD, Principal Investigator George A Macones, MD, MSCE, Principal Investigator Alison G Cahill, MD, MSCI, Principal Investigator Molly J Stout, MD, MSCI, Principal Investigator
Additional Information
Related publications: Lyell DJ, Pullen KM, Mannan J, Chitkara U, Druzin ML, Caughey AB, El-Sayed YY. Maintenance nifedipine tocolysis compared with placebo: a randomized controlled trial. Obstet Gynecol. 2008 Dec;112(6):1221-6. doi: 10.1097/AOG.0b013e31818d8386. Likis FE, Edwards DR, Andrews JC, Woodworth AL, Jerome RN, Fonnesbeck CJ, McKoy JN, Hartmann KE. Progestogens for preterm birth prevention: a systematic review and meta-analysis. Obstet Gynecol. 2012 Oct;120(4):897-907. Review. Hassan SS, Romero R, Vidyadhari D, Fusey S, Baxter JK, Khandelwal M, Vijayaraghavan J, Trivedi Y, Soma-Pillay P, Sambarey P, Dayal A, Potapov V, O'Brien J, Astakhov V, Yuzko O, Kinzler W, Dattel B, Sehdev H, Mazheika L, Manchulenko D, Gervasi MT, Sullivan L, Conde-Agudelo A, Phillips JA, Creasy GW; PREGNANT Trial. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2011 Jul;38(1):18-31. doi: 10.1002/uog.9017. Epub 2011 Jun 15. Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH; Fetal Medicine Foundation Second Trimester Screening Group. Progesterone and the risk of preterm birth among women with a short cervix. N Engl J Med. 2007 Aug 2;357(5):462-9. Borna S, Sahabi N. Progesterone for maintenance tocolytic therapy after threatened preterm labour: a randomised controlled trial. Aust N Z J Obstet Gynaecol. 2008 Feb;48(1):58-63. doi: 10.1111/j.1479-828X.2007.00803.x. Arikan I, Barut A, Harma M, Harma IM. Effect of progesterone as a tocolytic and in maintenance therapy during preterm labor. Gynecol Obstet Invest. 2011;72(4):269-73. doi: 10.1159/000328719. Epub 2011 Nov 12.
Starting date: May 2013
Last updated: May 12, 2014
|