Preterm labor is a common and serious complication in pregnancy in the United States, occurring in approximately 400,000 pregnancies per year. Magnesium sulfate is currently the most commonly prescribed agent for tocolysis in the United States. However, up to 35% of patients treated with magnesium sulfate fail therapy. In this setting, the most common strategy in the United States is to add indomethacin as adjuvant therapy. Unfortunately, there are no data to support that this strategy will improve outcome. In addition, recent data suggested that neonatal outcome may be worsened when indomethacin is used in this setting. The goal of the project is to use a randomized clinical trial to test the hypothesis that indomethacin, when used for adjuvant tocolysis in preterm labor (i.e., in those who are failing to respond to conventional first-line therapy) can decrease the rate of major neonatal complications and death. The proposed research project will use a double-blind, parallel, randomized, controlled clinical trial design to compare the efficacy of indomethacin to placebo for adjuvant tocolysis in pregnancies less than 30 weeks gestation. Patients will be recruited for this study from the Labor and Delivery wards of the Hospital of the University of Pennsylvania, Pennsylvania Hospital, Thomas Jefferson University Hospital, and Christiana Care Health Services. Patients who fail first-line therapy with magnesium sulfate will be evaluated for possible enrollment into this randomized clinical trial. Those who give informed consent will be enrolled into the study. This study calls for the enrollment of 205 patients in both arms. Patients will be randomized to receive either indomethacin rectal suppositories (50 mg every 6 hours) or identical-appearing placebo suppositories for a maximum of 48 hours. After completion of treatment with either placebo or indomethacin, patient care will be largely at the discretion of the attending physicians. Many prior studies of tocolysis have used variable periods of delay in delivery as the primary outcome measure. The investigators believe that this is not the appropriate primary endpoint, since the ultimate goal of tocolysis is to improve neonatal outcome. Thus, although delivery delay will be analyzed as a secondary endpoint, the primary outcome (on which the sample size is based) will be based on neonatal morbidity. Specifically, the primary outcome measure for this study will be a dichotomous composite neonatal morbidity/mortality outcome measure. A neonate will be classified as having an adverse neonatal outcome if he/she suffers from any major morbid condition (defined as necrotizing enterocolitis, death, intraventricular hemorrhage, respiratory distress syndrome, or chronic lung disease). Secondary outcomes for analysis will include: (1) time from randomization until delivery, (2) mean gestational age at delivery, (3) major maternal side effects, (4) need for re-admission for tocolysis, (5) infant birth weight, and others.
| Macones, G A; Marder, S J; Clothier, B et al. (2001) The controversy surrounding indomethacin for tocolysis. Am J Obstet Gynecol 184:264-72 |
