Ibuprofen vs. Continuous Indomethacin in the Treatment of PDA
|Patent Ductus Arteriosus||Drug: Continuous indomethacin Drug: ibuprofen||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Comparison of Intravenous Ibuprofen vs. Continuous Indomethacin in the Treatment of Patent Ductus Arteriosus|
- To show no differences in urine output and/or in serum creatinine between the treatment groups [ Time Frame: Up to one day after completion of therapy ]
- To show no other clinical differences, eg. NEC, IVH or ROP between the groups; to study doppler flow velocities to these areas; to correlate with BNP levels. [ Time Frame: Until end of primary hospitalization ]
|Study Start Date:||February 2002|
|Study Completion Date:||September 2006|
Despite the fact that ibuprofen appears to minimize the renal side effects seen following bolus indomethacin, other concerns regarding both short and long-term safety remain. Indomethacin, on the other hand, has been used to treat premature neonates for many years. Other than transient vasoconstrictive effects, no significant toxicity has been noted. Thus, if we were to be able to eliminate the differential renal effects, indomethacin would remain, for many, the therapy of choice for the premature neonate with a persistent PDA. We hypothesized that continuous administration of indomethacin would provide this option. Ibuprofen therapy has not, to date, been compared with indomethacin administered by continuous infusion. Hence, in the current study we attempted to determine whether continuous indomethacin administration could potentially offer the same advantages as ibuprofen in treating PDA, specifically in terms of mitigation of renal side effects. Specifically, our primary objective was to show no differences in urine output and/or in serum creatinine between the treatment groups. As a secondary objective, we aimed to show no other potentially vascular-mediated clinical differences, eg. Necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), retinopathy of prematurity (ROP) and on bilirubin albumin binding between the groups.
B-type natriuretic peptide (BNP) is released by ventricular myocytes in response to ventricular volume load. It, in turn, mediates vasodilation, natriuresis and diuresis. Serum BNP levels have been shown to be clinically useful in differentiating between respiratory and cardiac disease, in monitoring heart failure therapies and in serving as early diagnostic biomarkers of ductal patency in premature neonates. As secondary objectives we intend to determine whether a decrease in BNP levels would be an equally reliable indicator of therapeutic efficacy in infants treated with ibuprofen as with indomethacin.In addition we will look at comparative effects on other vascular beds which might mediate long term side effects described above.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00485160
|Shaare Zedek Medical Center|
|Principal Investigator:||Cathy Hammerman, MD||Shaare Zedek Medical Center|