Official Title: “A Double-Blinded Randomized Controlled Trial With Indomethacin Versus Placebo in Women With Preterm Premature Rupture of Membranes (PPROM) Between 24 and 32 Weeks Gestation”

The purpose of this study is to determine if the short term use of indomethacin will reduce the number of women delivering within 48 hours when given to women with preterm premature rupture of membranes (PPROM) between 24- 32 weeks of gestation. We hypothesize that indomethacin's anti-inflammatory and tocolytic action will reduce the number of women delivering within 48 hours when given to women with PPROM between 24-32 weeks of gestation.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: April 2010

Preterm premature rupture of membranes (PPROM) is defined as rupture of the chorioamniotic membranes before the onset of labor prior to 37 weeks of gestation. The etiology of PPROM is not well understood but likely to be multifactorial. Although the underlying mechanism of PPROM is unknown, some speculate it is the human's inflammatory response to bacterial infection with the subsequent production of prostaglandins which weaken the fetal membranes.

Therefore, the use of indomethacin, a prostaglandin inhibitor, may decrease prostaglandin synthesis leading to less uterine irritability and prevention of weakened membranes.

This is a double blind randomized controlled trial comparing indomethacin to placebo in women with PPROM between the gestational ages of 24-32 weeks. Women between the gestational age of 24 to 32 weeks with premature rupture of membranes and not in active labor will be eligible for this clinical trial. After informed consent, patients will be randomized to either indomethacin or placebo. Maternal and neonatal outcomes will be assessed.

Intervention(s) in this Clinical Trial

• Drug: indomethacin
  • Indomethacin 50mg PO followed by 25mg PO q6hrs

Primary Measures

• Prolongation of pregnancy (interval from time of randomization to time of delivery) for 48 hours
  • Time Frame: 48 hours
    Safety Issue?: No

Secondary Measures

• Prolongation of pregnancy for 7 days
  • Time Frame: 7 days
    Safety Issue?: No
• Neonatal Morbidities: birth weight, APGAR scores, sepsis, respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), NICU hospitalization days, patent ductus arteriosus (PDA)
  • Time Frame: from admission/birth
    Safety Issue?: No
• Maternal outcomes: chorioamnionitis, endometritis, labor induction, placental abruption, cesarean section
  • Time Frame: from admission
    Safety Issue?: No

Inclusion Criteria:

• Gestational age between 24 0/7 - 31 5/7 weeks by LMP or ultrasound
• Documentation of rupture by demonstrating pooling or 2/3 diagnostic tests (pooling, ferning and nitrazine positivity)

Exclusion Criteria:

• Membrane rupture greater than 72 hours
• Persistent labor characterized by regular painful contractions with cervical change and/or cervix visually greater than 5 cm
• Chorioamnionitis defined by having 2 or more of the following: maternal temperature >
• 100.4, persistent fetal tachycardia (>170bpm), maternal tachycardia (>110bpm) in the absence of other likely cause, uterine tenderness.
• Non-reassuring fetal heart rate tracing or biophysical testing
• Vaginal hemorrhage
• Lethal fetal anomalies
• Intrauterine fetal demise
• Maternal conditions which precludes expectant management
• Fetal condition which precludes expectant management
• Maternal allergy to indomethacin
• Maternal active gastritis
• Multiple gestations
• HIV with viral load >1000
• HSV with active herpetic lesions
• Cervical cerclage

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 15 Years

Maximum Age for this Clinical Trial: 50 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Thomas Jefferson University

Overall Clinical Trial Officials and Contacts

Jolene S Seibel-Seamon, MD Principal Investigator Thomas Jefferson University  

Overall Contact: Jolene S Seibel-Seamon, MD 215-955-9239 joleneseibel@yahoo.com

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00466128

Study ID Number: 06U.528

ClinicalTrials.gov Identifier: NCT00466128

Health Authority: United States: Institutional Review Board