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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2010 by China Medical University Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
China Medical University Hospital
ClinicalTrials.gov Identifier:
NCT01149564
First received: June 20, 2010
Last updated: June 22, 2010
Last verified: June 2010
  Purpose

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.


Condition Intervention Phase
Extremely Premature Infants
PDA
Oral Ibuprofen
IV Ibuprofen
Drug: iv ibuprofen
Drug: oral ibuprofen
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Comparison of Oral and Intravenous Ibuprofen for Treatment of Patent Ductus Arteriosus in Extremely Premature Infants: A Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by China Medical University Hospital:

Primary Outcome Measures:
  • The primary outcome is to ascertain whether oral ibuprofen is effective and safe in inducing PDA closure in extremely premature infants. [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
    Number of extremely premature infants with PDA closed or Adverse Events as a Measure of efficiency and safety.


Secondary Outcome Measures:
  • A secondary objective is to compare the complications between infants treated with oral ibuprofen and those treated with IV ibuprofen. [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
    Number of extremely premature infants in each group with PDA closed or Adverse Events as a Measure of efficiency and safety.


Estimated Enrollment: 70
Study Start Date: December 2009
Estimated Study Completion Date: June 2012
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 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.
Drug: iv ibuprofen
Active Comparator: Oral ibuprofen Drug: oral ibuprofen

  Eligibility

Ages Eligible for Study:   up to 24 Hours
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01149564

Contacts
Contact: Bai-Horng Su, MD, PhD 886-4-22052121 ext 2061 bais@ms49.hinet.net

Locations
Taiwan
China Medical University Hospital Recruiting
Taichung, Taiwan, 404
Contact: Bai-Horng Su, MD, PhD    886-4-22052121 ext 2531    bais@ms49.hinet.net   
Principal Investigator: Bai-Horng Su, MD, PhD         
Sub-Investigator: Ming-Shia Lin, MD         
Sponsors and Collaborators
China Medical University Hospital
Investigators
Study Chair: Bai-Horng Su, MD, PhD China Medical University Hospital, Taiwan
  More Information

No publications provided

Responsible Party: Chairman of Department of Pediatrics, China Medical University
ClinicalTrials.gov Identifier: NCT01149564     History of Changes
Other Study ID Numbers: DMR-99, DMR-98
Study First Received: June 20, 2010
Last Updated: June 22, 2010
Health Authority: Taiwan: Department of Health

Additional relevant MeSH terms:
Ductus Arteriosus, Patent
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities
Ibuprofen
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 31, 2014