Indomethacin Versus Nifedipine for Preterm Labor Tocolysis

Study Overview
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Brief Summary
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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
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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.

Official Title
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Indocin Versus Nifedipine for Preterm Labor Tocolysis - A Randomized Double-Blinded Clinical Trial

Conditions
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Obstetric Labor, Premature

Intervention / Treatment
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* Drug: Indomethacin
* Drug: Nifedipine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Indomethacin<br>50 mg. oral Indomethacin initially, followed by 25 mg every 6 hrs for 48 hrs. | Drug: Indomethacin<br>* One 50 mg tablet of Indomethacin plus 2 pills of placebo followed by one 25 mg tablet of oral indomethacin every 6 hrs for 48 hrs.<br>|
| Active Comparator: Nifedipine<br>30 mg Nifedipine initially followed by 20 mg every 6 hrs for 48 hrs. | Drug: Nifedipine<br>* Three 10 mg tablets of Nifedipine followed by one 20 mg tablet every 6 hrs for 48 hrs.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Count of Patients With Recurrent Preterm Labor Within Two Weeks of Randomization | 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. | Two weeks after enrolled and randomized, up to 37 weeks of pregnancy | 

Secondary Outcome Measures

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