Ibuprofen vs. Continuous Indomethacin in the Treatment of PDA

Phase 3

Completed

• Conditions: Patent Ductus Arteriosus

• Registration Number: NCT00485160
• Lead Sponsor: Shaare Zedek Medical Center

Brief Summary

The purpose of this study is to determine whether closure of the PDA in premature neonates using IV ibuprofen vs continuous IV indomethacin has different side effects, eg. effects on renal function, on blood flow velocity in the superior mesenteric artery, the anterior cerebral artery, and the renal artery.

Detailed Description

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.

Study Timeline

• Study Start: 2002-02
• Study Completion: 2006-09
• Status Verified: 2007-06
• Study First Submitted: 2007-06-11
• Study First Submitted QC: 2007-06-11
• Study First Posted: 2007-06-12
• Last Update Submitted: 2011-07-20
• Last Update Posted: 2011-07-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

• < 1500 gm birth weight with PDA confirmed by echocardiography

Exclusion Criteria

• Additional congenital heart lesions
• Significant congenital malformations
• Documented infection
• Thrombocytopenia (<60,000)
• IVH grade 4

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
To show no differences in urine output and/or in serum creatinine between the treatment groups	Up to one day after completion of therapy

Secondary Outcome Measures

Name	Time	Method
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.	Until end of primary hospitalization

Trial Locations

Locations (1)

Shaare Zedek Medical Center; 🇮🇱 Jerusalem, Israel