Comparison of Oral and Intravenous Ibuprofen for PDA Treatment in Premature Infants

NCT ID: NCT01149564

Last Updated: 2010-06-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2012-06-30

Brief Summary

Background:

Patent ductus arteriosus (PDA) continues to be one of the most common problems in premature infants. Pharmacological closure of PDA with intravenous (IV) indomethacin was first reported in 1976, however, concern remains regarding the safety of indomethacin, which affects renal, GI and cerebral perfusion and may lead to complications such as transient or permanent renal dysfunction, NEC, GI hemorrhage, and reduced cerebral oxygenation. Recently, IV ibuprofen has been shown to be effective for the closure of patent ductus arteriosus in premature infants, without reducing mesenteric, renal, or cerebral blood flow. We have developed the echocardiographic PDA flow pattern as a guide for PDA treatment, fewer doses of drugs were needed to achieve acceptable closing rates. We have also reported that IV ibuprofen is as effective as IV indometacin for the PDA treatment in extremely premature infants, without increasing the incidence of complications in a randomised controlled trial. Several studies reported that oral ibuprofen may be effective for PDA treatment. To date there is no firm conclusion as to the efficacy and safety of oral ibuprofen compared with IV ibuprofen for PDA closure in extremely premature infants.

Objective:

Since the efficacy of pharmacological closure of PDA is related to gestational age, and extremely premature infants carry the highest rate of mortality and morbidity. We intend to conduct a randomized controlled trial to compare oral and intravenous ibuprofen for treatment of PDA in this high-risk population of extremely premature infants.

Methods:

Extremely premature infants (gestational age < 28 weeks) admit to the NICU will be eligible for enrollment. Informed parental consent will be obtained according to the Institutional Review Board's instructions. Extremely premature infants with respiratory distress syndrome (RDS) and PDA confirmed by echocardiography will be randomly assigned to receive either oral or IV ibuprofen. The subsequent doses of ibuprofen are also determined according to our specific echocardiographic PDA flow patterns at intervals of once every 24 hours from the last dose. The dosage of oral or ibuprofen is 10 mg/kg (1 ml) and then 5 mg/kg at 24-hour intervals as indicated by echocardiographic PDA flow pattern.

Sample Size Calculation and Length of the Study Period:

About 50-60 extremely premature infants will be admitted to our NICU each year. To prove with McNemar's Test at a one-sided significance level of 5% and a power of 90% that using oral ibuprofen instead of IV ibuprofen results in comparable PDA closure rates, only 31 extremely premature infants with RDS and PDA have to be enrolled. Allowing for attrition and exclusion from the final study groups, the length of the study period will be safe to set to 2 years.

Expected Results:

We expect to determine whether oral ibuprofen is effective and safe in inducing PDA closure in extremely premature infants and to compare the complications between infants treated with oral ibuprofen and those with IV ibuprofen.

Conditions

Extremely Premature Infants; PDA; Oral Ibuprofen; IV Ibuprofen

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

IV ibuprofen

The first dose of either oral or IV ibuprofen will be given at the time the patient is randomized.The subsequent doses of indometacin or ibuprofen are also determined according to the echocardiographic PDA flow patterns at intervals of once every 24 hours from the last dose. The dosage of both oral ibuprofen (Ibuprofen suspension, 20 mg/ml, Yung Shing Co., Taiwan) and IV ibuprofen (PedeaR 20 mg/ml, developed by Orphan Europe and approved by the EMEA) are an initial dose of 10 mg/kg and then 5 mg/kg at 24-hour intervals as indicated by PDA flow pattern.

Group Type: PLACEBO_COMPARATOR

iv ibuprofen

Intervention Type: DRUG

Oral ibuprofen

Group Type: ACTIVE_COMPARATOR

oral ibuprofen

Intervention Type: DRUG

Interventions

iv ibuprofen

Intervention Type: DRUG

oral ibuprofen

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• premature infants gestational age < 28 weeks, respiratory distress syndrome requiring assisted ventilation, a PDA without other cardiac anomalies confirmed by echocardiography within 24 hours after birth,

Exclusion Criteria

• severe congenital anomalies or lethal cardiopulmonary conditions, and informed consent could be obtained from parents

• Minimum Eligible Age: 3 Hours
• Maximum Eligible Age: 24 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

China Medical University Hospital

OTHER

Sponsor Role: lead

Responsible Party

China Medical University

Principal Investigators

Bai-Horng Su, MD, PhD

Role: STUDY_CHAIR

China Medical University Hospital

Locations

China Medical University Hospital

Taichung, , Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Bai-Horng Su, MD, PhD

Role: CONTACT

bais@ms49.hinet.net

886-4-22052121 ext. 2061

Facility Contacts

Bai-Horng Su, MD, PhD

Role: primary

bais@ms49.hinet.net

886-4-22052121 ext. 2531

Other Identifiers

DMR-98

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

DMR-99

Identifier Type: -

Identifier Source: org_study_id