Brief Title
Comparison of Oral and Intravenous Ibuprofen for PDA Treatment in Premature Infants
Official Title
Comparison of Oral and Intravenous Ibuprofen for Treatment of Patent Ductus Arteriosus in Extremely Premature Infants: A Randomized Controlled Trial
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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
The primary outcome is to ascertain whether oral ibuprofen is effective and safe in inducing PDA closure in extremely premature infants.
Secondary Outcome
A secondary objective is to compare the complications between infants treated with oral ibuprofen and those treated with IV ibuprofen.
Condition
Extremely Premature Infants
Intervention
iv ibuprofen
Study Arms / Comparison Groups
IV ibuprofen
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
70
Start Date
December 2009
Completion Date
June 2012
Primary Completion Date
June 2012
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
Gender
All
Ages
N/A - 24 Hours
Accepts Healthy Volunteers
No
Contacts
Bai-Horng Su, MD, PhD, 886-4-22052121, [email protected]
Location Countries
Taiwan
Location Countries
Taiwan
Administrative Informations
NCT ID
NCT01149564
Organization ID
DMR-99
Secondary IDs
DMR-98
Study Sponsor
China Medical University Hospital
Study Sponsor
Bai-Horng Su, MD, PhD, Study Chair, China Medical University Hospital,Taiwan
Verification Date
June 2010