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

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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