Clinical trial NCT02438371: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Preterm Labor
Keywords: pregnancy
preterm labor
tocolysis
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
First posted: 2015-05-08
Enrollment: 49
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Number of Maternal Participants Who Achieve 48 Hours of Pregnancy Prolongation
timeFrame: 48 hours after administration of tocolytic agent
Secondary outcomes:
measure: Number of Maternal Participants Who Achieve 7 Days of Pregnancy Prolongation
timeFrame: 7 days after administration of tocolytic agent
measure: Number of Days From First Dose of Tocolytic Agent to Delivery
timeFrame: from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months)
measure: Neonatal Birthweight
timeFrame: at the time of birth
measure: Neonatal Sex
timeFrame: at the time of birth
measure: Number of Neonates Who Were Admitted to the Neonatal Intensive Care Unit (NICU)
timeFrame: from birth until hospital discharge or day 120 of life (whichever occurs first)
measure: Neonatal Length of Stay in NICU
timeFrame: from birth until hospital discharge or day 120 of life (whichever occurs first)
measure: Neonatal Length of Hospital Stay
timeFrame: from birth until hospital discharge or day 120 of life (whichever occurs first)
measure: Number of Neonatal Deaths
timeFrame: from birth until hospital discharge or day 120 of life (whichever occurs first)
measure: Number of Neonates With Intraventricular Hemorrhage Diagnosed Using Cranial Ultrasonography
timeFrame: from birth until hospital discharge or day 120 of life (whichever occurs first)
measure: Number of Neonates With Necrotizing Enterocolitis
timeFrame: from birth until hospital discharge or day 120 of life (whichever occurs first)
measure: Number of Neonates With Culture-positive Sepsis
timeFrame: from birth until hospital discharge or day 120 of life (whichever occurs first)
measure: Number of Neonates With Seizures
timeFrame: from birth until hospital discharge or day 120 of life (whichever occurs first)
measure: Number of Neonates Who Needed Mechanical Ventilation
timeFrame: from birth until hospital discharge or day 120 of life (whichever occurs first)
measure: Neonatal Duration of Ventilator Use
timeFrame: from birth until hospital discharge or day 120 of life (whichever occurs first)
measure: Number of Neonates Who Received Continuous Positive Airway Pressure (CPAP)
timeFrame: from birth until hospital discharge or day 120 of life (whichever occurs first)
measure: Number of Maternal Participants Who Delivered by Cesarean Delivery
timeFrame: at the the time of birth
measure: Number of Maternal Participants Who Had Clinical Chorioamnionitis
timeFrame: from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months)
measure: Number of Maternal Participants Who Had Preterm Premature Rupture of Membranes (PPROM)
timeFrame: from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months)
measure: Number of Maternal Participants Who Had Preeclampsia
timeFrame: from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months)
measure: Number of Maternal Participants Who Needed Blood Transfusion
timeFrame: from time of birth to time of discharge from hospital (about 2-3 days)
measure: Number of Maternal Participants With Headache
timeFrame: from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)
measure: Number of Maternal Participants With Nausea
timeFrame: from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)
measure: Number of Maternal Participants With Vomiting
timeFrame: from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)
measure: Number of Maternal Participants With Acid Reflux
timeFrame: from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)
measure: Number of Maternal Participants With Hypotension
timeFrame: from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)
measure: Number of Maternal Participants With Tachycardia
timeFrame: from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)
measure: Number of Maternal Participants With Syncope
timeFrame: from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)
Other outcomes:
Locations:
city: Houston
country: United States
facility: Memorial Hermann Hospital Texas Medical Center
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Maria Hutchinson, M.S.
role: STUDY_DIRECTOR
References:
citation: 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.