Log in to MyACC
Comparison of Ibuprofen and Indomethacin for Closure of Patent Ductus Arteriosus - Ibuprofen and Indomethacin for Closure of Patent Ductus Arteriosus
Description:
This study was a multicenter randomized trial designed to determine whether, among preterm infants with patent ductus arteriosus (PDA), ibuprofen or indomethacin would be more effective or safe for PDA closure.
Hypothesis:
Ibuprofen is as effective as indomethacin for treatment of PDA, and is associated with fewer side effects.
Study Design
Study Design:
Patients Enrolled: 148
Mean Follow Up: 30 days
Mean Patient Age: 2-4 days
Patient Populations:
Gestational age 32 weeks or less, age 2-4 days, echocardiographic evidence of PDA, and respiratory distress syndrome necessitating mechanical ventilation
Exclusions:
Major congenital anomalies; life-threatening infection or hydrops fetalis; recent intraventricular hemorrhage; urine output below 1 ml/kg/h; serum creatinine >1.6 mg/dl; serum urea nitrogen >40 mg/dl; platelet count of <60,000 per cubic millimeter; tendency to bleed, as revealed by hematuria, blood in the endotracheal aspirate, gastric aspirate, or stools, and oozing from puncture sites; and hyperbilirubinemia necessitating exchange transfusion
Primary Endpoints:
Rate of PDA closure
Secondary Endpoints:
30-day mortality, urine output
Drug/Procedures Used:
Preterm infants with respiratory distress syndrome and PDA confirmed by echocardiography were enrolled. Subjects were randomly assigned to receive three doses of either intravenous indomethacin (0.2 mg/kg at 12-hour intervals) (n=74) or ibuprofen (an initial dose of 10 mg/kg, followed by two doses of 5 mg/kg, 24 and 48 hours later) (n=74).
If there was continued evidence of PDA by echocardiography following completion of randomly assigned treatment, nonrandomized rescue therapy with intravenous indomethacin was administered. If the second pharmacologic intervention still failed to promote PDA closure in a mechanically ventilated patient, surgical ligation of PDA was recommended.
Concomitant Medications:
Intravenous fluid, furosemide (if needed after the first week), dopamine for hypotension, oxygen, lung surfactant (if necessary), and prophylactic antibiotics
Principal Findings:
Mean gestational age and birth weight was similar in both groups (29 weeks and 1230 g, respectively).
Randomized treatment with indomethacin and ibuprofen was associated with a similar rate of PDA closure (66% vs. 70%, p=0.41). Nine infants in the indomethacin group, and 12 infants in the ibuprofen group had to be administered rescue therapy (12% vs. 16%, p=0.48). Additionally, indomethacin and ibuprofen therapy was associated with similar rate of need for surgical PDA ligation (12% vs. 14%, p=0.81).
Mortality at 30 days was similar between infants in the indomethacin and ibuprofen groups (8% vs. 9%, p=0.76). Fourteen infants in the indomethacin group and five infants in the ibuprofen group developed oliguria (19% vs. 7%, p=0.03) during the three days beginning with the start of treatment.
Interpretation:
Among preterm neonates with PDA and respiratory distress, treatment with intravenous ibuprofen and indomethacin was associated with similar rates of PDA closure. In addition, treatment with ibuprofen was associated with less oliguria, as compared to indomethacin.
References:
Van Overmeire B, Smets K, Lecoutere D, et al. A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus. N Engl J Med 2000;343:674-81.
Keywords: Birth Weight, Gestational Age, Ligation, Infant, Newborn, Cyclooxygenase Inhibitors, Respiration, Artificial, Ibuprofen, Infant, Premature, Oliguria, Indomethacin, Ductus Arteriosus, Patent, Echocardiography
< Back to Listings
