Nifedipine or Nifedipine Plus Indomethacin for Treatment of Acute Preterm Labor

Nifedipine Alone or Nifedipine Plus Indomethacin for Treatment of Acute Preterm Labor: An Open Label, Randomized Comparative Effectiveness Controlled Trial

Tocolytic agents are used for the treatment of preterm labor. It is unclear whether combination treatments of two tocolytic agents are more effective in stopping preterm labor compared to one. Therefore, the investigators propose a comparative effective trial of nifedipine plus indomethacin vs. nifedipine alone for the treatment of preterm labor

Study Overview

• Status: Terminated
• Conditions: Preterm Labor
• Intervention / Treatment: Drug: Nifedipine; Drug: Indomethacin

Detailed Description

The investigators current treatment for preterm labor has not been shown to be effective in prolonging pregnancy sufficiently to improve neonatal outcomes and other treatment strategies are needed. Multiple examples demonstrate that multi-agent treatments are routine clinical practice in other fields of medicine including chemotherapeutics for cancer, multi-therapeutics for myocardial infarction and broad spectrum antibiotics for pneumonia. At this time, it is unclear if a combination of tocolytic medications for preterm labor is more advantageous for women. If pregnancy is prolonged with combined tocolytic therapy, this could directly influence the treatment of preterm labor and potentially improve neonatal outcomes. There currently are no trials of combination regimens using widely used tocolytic agents, such as nifedipine and indomethacin. Thus, we propose a comparative effective trial of nifedipine plus indomethacin vs. nifedipine alone for the treatment of preterm labor

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Memorial Hermann Hospital Texas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• We will include pregnant women between 22 0/7 to 31 6/7 weeks gestation who present with regular uterine contractions defined as at least one contraction every 10 minutes for 30 minutes with at least one of the following:
• cervical change of at least 1 cm or
• cervical dilation of 2 cm at the time of initial exam or
• positive fetal fibronectin and transvaginal cervical length <2.5 cm

Exclusion Criteria:

• We will exclude pregnant women with any contraindication to tocolysis:
• clinical chorioamnionitis (defined as a temperature of >100.4 F and any of the following: fundal tenderness, maternal tachycardia, fetal tachycardia or purulent vaginal discharge)
• non reassuring fetal heart tones
• suspected placental abruption
• preterm premature rupture of membranes
• prior tocolytic treatment during the past 48 hours
• known adverse effect to indomethacin or nifedipine
• already receiving nifedipine for chronic hypertension

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nifedipine; Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours for a total of 48 hours.	Drug: Nifedipine; Other Names: Procardia
Active Comparator: Nifedipine plus Indomethacin; Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours for a total of 48 hours.	Drug: Nifedipine; Other Names: Procardia; Drug: Indomethacin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Maternal Participants Who Achieve 48 Hours of Pregnancy Prolongation	48 hours after administration of tocolytic agent

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Maternal Participants Who Achieve 7 Days of Pregnancy Prolongation		7 days after administration of tocolytic agent
Number of Days From First Dose of Tocolytic Agent to Delivery	Length of time from tocolytic initiation to the time of delivery	from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months)
Neonatal Birthweight		at the time of birth
Neonatal Sex		at the time of birth
Number of Neonates Who Were Admitted to the Neonatal Intensive Care Unit (NICU)		from birth until hospital discharge or day 120 of life (whichever occurs first)
Neonatal Length of Stay in NICU		from birth until hospital discharge or day 120 of life (whichever occurs first)
Neonatal Length of Hospital Stay		from birth until hospital discharge or day 120 of life (whichever occurs first)
Number of Neonatal Deaths		from birth until hospital discharge or day 120 of life (whichever occurs first)
Number of Neonates With Intraventricular Hemorrhage Diagnosed Using Cranial Ultrasonography		from birth until hospital discharge or day 120 of life (whichever occurs first)
Number of Neonates With Necrotizing Enterocolitis		from birth until hospital discharge or day 120 of life (whichever occurs first)
Number of Neonates With Culture-positive Sepsis		from birth until hospital discharge or day 120 of life (whichever occurs first)
Number of Neonates With Seizures		from birth until hospital discharge or day 120 of life (whichever occurs first)
Number of Neonates Who Needed Mechanical Ventilation		from birth until hospital discharge or day 120 of life (whichever occurs first)
Neonatal Duration of Ventilator Use		from birth until hospital discharge or day 120 of life (whichever occurs first)
Number of Neonates Who Received Continuous Positive Airway Pressure (CPAP)		from birth until hospital discharge or day 120 of life (whichever occurs first)
Number of Maternal Participants Who Delivered by Cesarean Delivery		at the the time of birth
Number of Maternal Participants Who Had Clinical Chorioamnionitis		from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months)
Number of Maternal Participants Who Had Preterm Premature Rupture of Membranes (PPROM)		from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months)
Number of Maternal Participants Who Had Preeclampsia		from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months)
Number of Maternal Participants Who Needed Blood Transfusion		from time of birth to time of discharge from hospital (about 2-3 days)
Number of Maternal Participants With Headache		from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)
Number of Maternal Participants With Nausea		from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)
Number of Maternal Participants With Vomiting		from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)
Number of Maternal Participants With Acid Reflux		from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)
Number of Maternal Participants With Hypotension		from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)
Number of Maternal Participants With Tachycardia		from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)
Number of Maternal Participants With Syncope		from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Investigators: Study Director: Maria Hutchinson, M.S., The University of Texas Health Science Center, Houston

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:CD014978. doi: 10.1002/14651858.CD014978.pub2. Review.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): October 10, 2019
• Study Completion (Actual): October 10, 2019

Study Registration Dates

• First Submitted: May 5, 2015
• First Submitted That Met QC Criteria: May 7, 2015
• First Posted (Estimate): May 8, 2015

Study Record Updates

• Last Update Posted (Actual): November 24, 2021
• Last Update Submitted That Met QC Criteria: October 25, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: pregnancy; preterm labor; tocolysis
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Premature Birth; 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: HSC-MS-15-0134

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No