Nifedipine or Nifedipine Plus Indomethacin for Treatment of Acute Preterm Labor

Study Overview
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Brief Summary
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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
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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

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

Conditions
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Preterm Labor

Intervention / Treatment
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* Drug: Nifedipine
* Drug: Indomethacin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nifedipine<br>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<br> <br> * Other names: Procardia;|
| Active Comparator: Nifedipine plus Indomethacin<br>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<br> <br> * Other names: Procardia;Drug: Indomethacin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pregnancy, preterm labor, tocolysis