Timing of PDA Closure and Respiratory Outcome in Premature Infants

This study has been terminated.
(Lack of availability of IV ibuprofen as of 8/10 due to a manufacturer's recall)
Sponsor:
Collaborator:
H. Lundbeck A/S
Information provided by (Responsible Party):
Ilene R.S. Sosenko, M.D., University of Miami
ClinicalTrials.gov Identifier:
NCT00802685
First received: December 4, 2008
Last updated: January 3, 2014
Last verified: December 2013
  Purpose

The investigators propose the present study with the following aims:

  • to determine whether early patent ductus arteriosus (PDA) treatment with ibuprofen treatment at the onset of clinical symptoms is superior to late ibuprofen treatment only when symptoms of a hemodynamically significant PDA are present in the evolution of bronchopulmonary dysplasia (BPD) defined as duration of supplemental oxygen exposure during the first 28 days
  • to determine whether early PDA treatment with ibuprofen will be superior to late treatment with ibuprofen in efficacy of PDA closure, need for rescue therapy, need for PDA ligation and incidence of major complications of prematurity.

Hypothesis: Early pharmacologic closure of PDA with ibuprofen will improve respiratory course and reduce BPD as reflected by a reduction in duration of supplemental oxygen during the first 28 days of age vs. late pharmacologic treatment with ibuprofen.

Outcome variables: The primary outcome of this study is the number of days spent on supplemental oxygen by each infant during the first 28 days.

Other outcomes to be determined between groups include:

  • Mortality
  • Other respiratory variables: total days on supplemental oxygen, days on mechanical ventilation, oxygen dependence at 36 weeks post menstrual age, age at final extubation.
  • Other respiratory complications: pneumothorax, pulmonary interstitial emphysema, need for high frequency ventilation, pulmonary hypertension
  • Efficacy of PDA closure: number of courses of medication required, need for ligation
  • Other neonatal complications: intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), intestinal perforation, sepsis, renal dysfunction (oliguria, elevated creatinine)
  • Time to achieving full enteral feedings, time to regain birth weight, weight at discharge.
  • Length of hospital stay

Condition Intervention
Patent Ductus Arteriosus
Drug: Early ibuprofen
Other: Late ibuprofen expectant group (placebo)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Timing of PDA Closure and Respiratory Outcome in Premature Infants

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • Days Spent on Supplemental Oxygen During the First 28 Days. [ Time Frame: 28 days of life ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Participants on Oxygen at 36 Weeks Postmenstrual Age [ Time Frame: at 36 weeks postmenstrual age ] [ Designated as safety issue: No ]

Enrollment: 105
Study Start Date: November 2007
Study Completion Date: February 2011
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: early ibuprofen

Drug: Early ibuprofen

IBUPROFEN DOSING SCHEDULE: At the diagnosis of PDA, infants randomized to "early treatment" will receive blinded ibuprofen initial dose 10 mg/kg, then two doses 5 mg/kg each, after 24 and 48 h, slow IV infusion. Initial therapy will be blinded. This group will then be eligible to receive unblinded, open label ibuprofen for a hemodynamically significant PDA include: SIGNS OF PDA + Presence of significant pulmonary hemorrhage ALONE OR SIGNS OF PDA +: Pulmonary edema, plus a large heart on CXR + one of the following: Hypotension, Respiratory failure (not due to something other than PDA) defined as at least two of the following respirator settings: Need for supplemental O2 > 50%; need IMV >40; need for PIP > 20; or need for HFOV.

Drug: Early ibuprofen
IBUPROFEN SCHEDULE: initial dose 10 mg/kg, then 2 doses 5 mg/kg each, after 24 and 48 h, slow IV infusion. Initial therapy is blinded. At PDA diagnosis, infants randomized to "early treatment" receive blinded ibuprofen. Infants randomized to "late treatment" receive blinded placebo. Hemodynamically significant PDA criteria: SIGNS OF PDA + pulmonary hemorrhage OR SIGNS OF PDA +: Pulmonary edema, plus a large heart on CXR + one of the following: Hypotension, Respiratory failure (due to PDA) defined as at least two of the following: Need for supplemental O2 > 50%; need IMV >40; need for PIP > 20; or need for HFOV. Once hemodynamically significant PDA criteria met, if echo is positive, infants from both groups can receive open label ibuprofen.
Late Ibuprofen expectant group (placebo)
Late ibuprofen expectant group (placebo): Ibuprofen schedule: At PDA diagnosis, infants randomized to "late expectant group" will receive blinded placebo. If hemo-dynamically significant PDA develops, infants now receive open label ibuprofen, initial dose of 10 mg/kg, then 2 doses 5 mg/kg each, after 24 and 48 h, slow IV infusion. Signs of a hemodynamically significant PDA: Signs of PDA + pulmonary hemorrhage alone or Signs of PDA + Pulmonary edema, plus a large heart on CXR + one of the following: Hypotension, Respiratory failure (due to PDA) defined as at least two of the following respirator settings: Need for supplemental O2 > 50%; need IMV >40; need for PIP > 20; or need for HFOV. Infants who had received placebo will ibuprofen for the first time (thus, "late" ibuprofen or expectant).
Other: Late ibuprofen expectant group (placebo)
Drug: Late ibuprofen expectant group (placebo): DOSING SCHEDULE: At PDA diagnosis infants randomized to "late ibuprofen expectant group" will receive blinded placebo. If hemodynamically significant PDA develops, infants now receive open label ibuprofen at an initial dose of 10 mg/kg, then two doses 5 mg/kg each, after 24 and 48 h, slow IV infusion. Signs of a hemodynamically significant PDA include: SIGNS OF PDA + pulmonary hemorrhage ALONE OR SIGNS OF PDA +: Pulmonary edema, plus a large heart on CXR + one of the following: Hypotension, Respiratory failure (due PDA) defined as at least 2 of the following settings: Need for supplemental O2 > 50%; need IMV >40; need for PIP > 20; or need for HFOV.

Detailed Description:

Study terminated when intravenous (IV) ibuprofen withdrawn for both clinical and research use.

  Eligibility

Ages Eligible for Study:   up to 14 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Inborn patients at JHS hospitals (admitted to the NICU at JMH within the first 72 hrs of age
  • BW 500-1250 grams
  • 23-32 wks gestational age
  • > 1d but < 14d of age.

Exclusion Criteria:

  • Major congenital malformations
  • Proven sepsis (positive blood culture)
  • Contraindications to the use of Ibuprofen or Indomethacin
  • Terminal condition, not expected to survive beyond 48 h
  • Infants born excessively SGA(3 S.D. below the mean for GA)
  • Infants with initial PDA presentation that is hemodynamically significant
  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: NCT00802685

Locations
United States, Florida
Jackson Memorial Hospital/Holtz Children's Center
Miami, Florida, United States, 33136
Sponsors and Collaborators
University of Miami
H. Lundbeck A/S
Investigators
Principal Investigator: Ilene RS Sosenko, MD University of Miami
  More Information

No publications provided by University of Miami

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ilene R.S. Sosenko, M.D., Professor of Pediatrics, University of Miami
ClinicalTrials.gov Identifier: NCT00802685     History of Changes
Other Study ID Numbers: 20070871
Study First Received: December 4, 2008
Results First Received: June 17, 2013
Last Updated: January 3, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Miami:
Patent ductus arteriosus
Respiratory outcome

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

ClinicalTrials.gov processed this record on October 29, 2014