Indomethacin Versus Nifedipine for Preterm Labor Tocolysis

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

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.

Study Overview

• Status: Completed
• Conditions: Obstetric Labor, Premature
• Intervention / Treatment: Drug: Indomethacin; Drug: Nifedipine

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.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Indomethacin; 50 mg. oral Indomethacin initially, followed by 25 mg every 6 hrs for 48 hrs.	Drug: Indomethacin; 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.
ACTIVE_COMPARATOR: Nifedipine; 30 mg Nifedipine initially followed by 20 mg every 6 hrs for 48 hrs.	Drug: Nifedipine; Three 10 mg tablets of Nifedipine followed by one 20 mg tablet every 6 hrs for 48 hrs.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Stanford University

Publications and helpful links

General Publications

• Wilson A, Hodgetts-Morton VA, Marson EJ, Markland AD, Larkai E, Papadopoulou A, Coomarasamy A, Tobias A, Chou D, Oladapo OT, Price MJ, Morris K, Gallos ID. Tocolytics for delaying preterm birth: a network meta-analysis (0924). Cochrane Database Syst Rev. 2022 Aug 10;8(8):CD014978. doi: 10.1002/14651858.CD014978.pub2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2007
• Primary Completion (ACTUAL): December 8, 2012
• Study Completion (ACTUAL): December 8, 2012

Study Registration Dates

• First Submitted: June 13, 2007
• First Submitted That Met QC Criteria: June 13, 2007
• First Posted (ESTIMATE): June 15, 2007

Study Record Updates

• Last Update Posted (ACTUAL): October 1, 2018
• Last Update Submitted That Met QC Criteria: August 31, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Gout Suppressants; Tocolytic Agents; Indomethacin; Nifedipine
• Other Study ID Numbers: 97873

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO