Indomethacin treatment for symptomatic patent ductus arteriosus: a double-blind control study.

A double-blind control study was designed to determine the efficacy and safety of indomethacin treatment of patients with symptomatic patent ductus arteriosus. Infants with severe respiratory distress syndrome and symptomatic patent ductus arteriosus were eligible for the prospective study if the ratio of left atrial/aortic root diameter remained greater than or equal to 1.3:1 following a 24-hour period of medical management. Thirty-nine eligible infants were randomly assigned to the control or indomethacin group and given 0.2 mg/kg of enteral indomethacin or placebo in a double-blind manner. Second and third doses were administered at 24-hour intervals in phase 1 (17 patients), and at eight-hour intervals in phase 2 (22 patients). The 75% patent ductus arteriosus closure rate with indomethacin treatment in phase 1 was not statistically significant due to a 44% spontaneous closure rate in the control group. In phase 2, however, 85% of the indomethacin group demonstrated patent ductus arteriosus closure vs only 11% in the matched control group (P less than .01). Although no indomethacin side effects occurred in phase 1, in phase 2 indomethacin administration was associated with minimal, but statistically significant, transient impaired renal function and, in three infants (23%), mild upper gastrointestinal bleeding. In summary, enteral administration of three 0.2 mg/kg indomethacin doses at eight-hour intervals thus appears to be a safe and effective alternative to surgical closure.