Comparison of Nifedipine Versus Indomethacin for Acute Preterm Labor

There are about 10 million births that occur before 37 weeks (prior to full term gestation)
that occur annually worldwide. More than 1 million infants die from complications related to
preterm birth. Tocolytics, medications that stop preterm labor, have been well studied.
Results regarding prolongation of pregnancy are varied, but tocolytics have been shown to
delay delivery for 48 hours, allowing time to administer corticosteroids. ACOG (American
Congress of Obstetrics and Gynecologists) recommends giving tocolytics to provide time for
corticosteroid administration, transfer to tertiary level care and to allow for magnesium
infusion to protect the neonatal brain. Corticosteroid administration when the course is
completed (48 hours from first dose) decreases some of the major risks associated with
prematurity.

Recent meta-analyses have shown of the commonly used tocolytics, calcium channel blockers and
prostaglandin inhibitors ranked consistently among the top three medications in several
categories including delaying delivery by 48 hours. There have been only two published
randomized control studies to date that have directly compared these two tocolytics. These
studies lacked power and standardization to provide clinical guidelines. There is a high
neonatal mortality and morbidity along with exceedingly high hospital costs associated with
complications related to preterm birth, so it is important to intervene with superior
medications. Here the investigators propose a multi institutional (based within the
University of California system) randomized controlled study to directly compare nifedipine
(most commonly used calcium channel blocker) to indomethacin (most commonly used
prostaglandin inhibitor).

Objective:

The Investigator's objective is to compare the prolongation of pregnancy by 48 hours after
women are diagnosed with preterm labor prior to 32 weeks gestational age and treated with
either nifedipine or indomethacin. Investigators hypothesize that indomethacin will
significantly arrest preterm labor by 48 hours in more women compared to nifedipine. The
primary outcomes measures will be delaying preterm delivery by 48 hours; secondary outcomes
measures will include delay of delivery by 7 days and decreasing delivery before 37 weeks.

Inclusion Criteria:

- Singleton pregnancy. A twin pregnancy reduced to singleton (either spontaneously or
therapeutically) before 140 weeks by gestational age (see dating below) is acceptable.

- Gestational age at randomization between 240 weeks to 315 weeks by using the dating
determinations as below

- Preterm labor with intact membranes. Preterm labor is defined as at least 6 regular
uterine contractions in 60 minutes either seen on tocodynamometer, palpated by health
providers and/or subjectively felt by the patient and at least one of the following:

1. Associated with cervical change by cervical dilation greater than or equal to 1cm
OR effacement greater than or equal to 25 to 50%

2. Cervix greater than or equal to 2cm dilated on initial digital exam

3. At least 75% effaced on initial digital exam

4. Short cervical length (defined by each institution's policy) as obtained by
transvaginal cervical sonography [in general, this is defined as a measurement of
2.0 - 2.5 cm or less] and/or a positive fetal fibronectin test (defined as a
level greater than 50ng/mL).

- Intact membranes

- 18 years of age or older

Exclusion Criteria:

- Fetal demise, or known major fetal anomaly, including cardiac anomaly and hydrops

- Maternal contraindication to nifedipine: preload cardiac lesions or maternal
hypotension (systolic blood pressure less than 100 or diastolic blood pressure less
than 60). A delayed dose can be given if blood pressure improves - it will be
documented if dose is delayed, how long from scheduled dose it was delayed and reason
for delay.

- Maternal contraindication to indomethacin: platelet dysfunction or bleeding disorders,
hepatic dysfunction, gastrointestinal ulcerative disease, renal dysfunction and asthma

- Obstetrical contraindication to tocolysis not already mentioned: non reassuring fetal
status, severe preeclampsia or eclampsia, maternal bleeding with hemodynamic
instability, chorioamnionitis, preterm premature rupture of membranes

- Participation in another interventional study that influences neonatal morbidity or
mortality

- Participation in this trial earlier in the pregnancy

- Maternal allergy to either indomethacin or nifedipine

- Maternal allergy to aspirin and other NSAIDs.

- Maternal hypertension requiring treatment.

- Maternal kidney disorder that would require adjustment in magnesium dosing.