Nifedipine or Nifedipine Plus Indomethacin for Treatment of Acute Preterm Labor

• ClinicalTrials.gov Identifier: NCT02438371
• Recruitment Status: Terminated
• First Posted: May 8, 2015
• Results First Posted: November 24, 2021
• Last Update Posted: November 24, 2021
• Sponsor: The University of Texas Health Science Center, Houston
• Information provided by (Responsible Party): Jerrie Refuerzo, The University of Texas Health Science Center, Houston

Tracking Information

• First Submitted Date: May 5, 2015
• First Posted Date: May 8, 2015
• Results First Submitted Date: October 25, 2021
• Results First Posted Date: November 24, 2021
• Last Update Posted Date: November 24, 2021
• Actual Study Start Date: May 2015
• Actual Primary Completion Date: October 10, 2019 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 25, 2021): Number of Maternal Participants Who Achieve 48 Hours of Pregnancy Prolongation [ Time Frame: 48 hours after administration of tocolytic agent ]
• Original Primary Outcome Measures (submitted: May 7, 2015): The percentage of women who remain pregnant [ Time Frame: 48 hours ]

Current Secondary Outcome Measures (submitted: October 25, 2021)

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

Original Secondary Outcome Measures (submitted: May 7, 2015)

Length of pregnancy [ Time Frame: up to 9 months ]

Length of time from tocolytic initiation to the time of delivery

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Nifedipine or Nifedipine Plus Indomethacin for Treatment of Acute Preterm Labor
• Official Title: Nifedipine Alone or Nifedipine Plus Indomethacin for Treatment of Acute Preterm Labor: An Open Label, Randomized Comparative Effectiveness Controlled Trial
• Brief Summary: 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
• 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
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Preterm Labor

Intervention

• Drug: Nifedipine
  Other Name: Procardia
• Drug: Indomethacin

Study Arms

• 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.
  Intervention: Drug: Nifedipine
• 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.
  Interventions:

  • Drug: Nifedipine
  • Drug: Indomethacin

• 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: October 25, 2021): 49
• Original Estimated Enrollment (submitted: May 7, 2015): 144
• Actual Study Completion Date: October 10, 2019
• Actual Primary Completion Date: October 10, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02438371
• Other Study ID Numbers: HSC-MS-15-0134
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Jerrie Refuerzo, The University of Texas Health Science Center, Houston
• Original Responsible Party: Same as current
• Current Study Sponsor: The University of Texas Health Science Center, Houston
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: The University of Texas Health Science Center, Houston
• Verification Date: October 2021