Indomethacin Versus Nifedipine for Preterm Labor Tocolysis

Phase 1

Completed

Brief Summary: Indomethacin and Nifedipine are commonly used medications for treatment of pre term labor. This study will compare the efficacy and adverse outcomes of oral nifedipine versus oral indomethacin for preterm labor tocolysis in an effort to identify which drug is most effective.

Patients diagnosed with preterm labor who grant consent will be randomized by the pharmacy to receive oral nifedipine or oral indomethacin. Both the patient and primary medical provider will be blinded to the identity of the study drug. An abdominal ultrasound will be performed in the labor and delivery unit prior to the administration of the tocolytic in order to assess fetal position and fluid level, and to document fetal cardiac activity and movement, and will be repeated at 48 hours post-randomization. Following randomization, the patient will be given either 50 mg oral indomethacin with two pills of placebo, or 3 pills each containing 10 mg oral nifedipine for a total of 30 mg. The patients will then receive either 25 mg of oral indomethacin every 6 hours for 48 hours, or 20 mg of oral nifedipine every 6 hours for 48 hours. Tocolysis beyond 48 hours will not be used.

Detailed Description: Patients presenting between 24-34 weeks gestation diagnosed with preterm labor who grant consent will be randomized by the pharmacy to receive oral nifedipine or oral indomethacin. Both the patient and primary medical provider will be blinded to the identity of the study drug. An abdominal ultrasound will be performed in the labor and delivery unit prior to the administration of the tocolytic in order to assess fetal position and fluid level, and to document fetal cardiac activity and movement, and will be repeated at 48 hours post-randomization. Following randomization, the patient will be given either 50 mg oral indomethacin with two pills of placebo, or 3 pills each containing 10 mg oral nifedipine for a total of 30 mg. The patients will then receive either 25 mg of oral indomethacin every 6 hours for 48 hours, or 20 mg of oral nifedipine every 6 hours for 48 hours. Tocolysis beyond 48 hours will not be used. Antibiotics and steroids for fetal lung maturity will be administered as per standard of care for preterm labor. Maternal side effects and delivery outcomes will be assessed from questionnaires administered by the study team following treatment, and/or from review of the patient's medical records.

Recruitment & Eligibility

Inclusion Criteria

Singleton and twin gestations
Intact amniotic membranes
No contra-indications to tocolysis
24-34 weeks gestation by last menstrual period and/or ultrasound
Documented cervical change, and regular painful uterine contractions at least every 5 minutes, or at least 2 cm cervical dilation and 80% effacement

Exclusion Criteria

Ruptured amniotic membranes
Signs/symptoms of chorioamnionitis (maternal temperature greater than 100.4 F/38.0 C, fetal tachycardia, uterine tenderness)
Non-reassuring fetal heart rate tracings
Contra-indications to indomethacin or nifedipine
Contra-indications to tocolysis

Arm && Interventions

Group	Intervention	Description
Indomethacin	Indomethacin	50 mg. oral Indomethacin initially, followed by 25 mg every 6 hrs for 48 hrs.
Nifedipine	Nifedipine	30 mg Nifedipine initially followed by 20 mg every 6 hrs for 48 hrs.

Primary Outcome Measures

Name	Time	Method
Count of Patients With Recurrent Preterm Labor Within Two Weeks of Randomization	Two weeks after enrolled and randomized, up to 37 weeks of pregnancy	Preterm labor was defined as documented cervical change and regular uterine contractions at least every 5 minutes, or at least 2 cm cervical dilation and 80% cervical effacement. Preterm labor is defined as uterine contractions occurring up to 37 weeks of pregnancy.

Secondary Outcome Measures

Name	Time	Method
Gestational Age at Delivery	Up to 42 weeks of pregnancy
Count of Participants With Neonatal Morbidity	Up to 42 weeks of pregnancy	Neonatal morbidity included admission to neonatal intensive care unit, respiratory distress or sepsis.
Neonatal Birthweight	Until discharge of mother and neonate from delivery hospital, up to 30 days after delivery	Birthweight is presented in grams
Days From First Medication Initiation to Delivery as a Measure of Delay in Delivery	Up to 42 weeks of pregnancy
Time to Uterine Quiescence	Up to 42 weeks of pregnancy	Uterine quiescence was defined as six or fewer uterine contractions per hour. Outcome was described as days.
Count of Participants With Side-effect Due to the Medication	Up to 42 weeks of pregnancy	Monitored side-effects for this outcome included abdominal pain, blood pressure change, GI-symptoms and skin rash.