Timing of PDA Closure and Respiratory Outcome in Premature Infants - Full Text View

Sponsor:	University of Miami
Collaborator:	H. Lundbeck A/S
Information provided by:	University of Miami
ClinicalTrials.gov Identifier:	NCT00802685

Purpose

The investigators propose the present study with the following aims:

to determine whether early PDA treatment with ibuprofen (specifically treatment at the onset of clinical symptoms) is superior to late ibuprofen treatment (specifically treatment only when symptoms of a hemodynamically significant PDA are present) in the evolution of BPD (defined as duration of supplemental oxygen exposure during the first 28 days), and
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: IVH, PVL, ROP, 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

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:

MedlinePlus related topics: Edema High Blood Pressure Low Blood Pressure Oxygen Therapy Premature Babies Sepsis

Drug Information available for: Ibuprofen

U.S. FDA Resources

Further study details as provided by University of Miami:

Primary Outcome Measures:

The primary outcome of this study is the number of days spent on supplemental oxygen by each infant during the first 28 days. [ Time Frame: 28 days of life ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Mortality; d on O2, d on ventilation, O2 dependence/36 wk PMA, age at extubation; pneumothorax, PIE, HFOV, pul hypertension; efficacy of PDA closure: # courses of medication, PDA ligation; IVH, PVL, ROP, NEC, intestinal perf, sepsis, renal dysfunction [ Time Frame: at hospital discharge ] [ 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 unblended, 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 DOSING SCHEDULE: 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. At the diagnosis of PDA, infants randomized to "early treatment" will receive blinded ibuprofen. Infants randomized to "late treatment" will receive blinded placebo. The criteria 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. Once hemodynamically significant PDA criteria met, if echo is positive, infants from both groups can receive open label ibuprofen; infants who had received placebo will be have ibuprofen for the first time (thus, "late" ibuprofen).
Late Ibuprofen expectant group Drug: Late ibuprofen expectant group IBUPROFEN DOSING SCHEDULE: At the diagnosis of PDA, infants randomized to "late ibuprofen expectant group" will receive blinded placebo. If criteria of a hemodynamically significant PDA develop, infants from this group can 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 + 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. Infants who had received placebo will be have ibuprofen for the first time (thus, "late" ibuprofen or expectant).	Other: Late ibuprofen expectant group Other: Late Ibuprofen expectant group Drug: Late ibuprofen expectant group IBUPROFEN DOSING SCHEDULE: At the diagnosis of PDA, infants randomized to "late ibuprofen expectant group" will receive blinded placebo. If criteria of a hemodynamically significant PDA develop, infants from this group can 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 + 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. Infants who had received placebo will be have ibuprofen for the first time (thus, "late" ibuprofen or expectant).

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 unblended, 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 DOSING SCHEDULE: 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. At the diagnosis of PDA, infants randomized to "early treatment" will receive blinded ibuprofen. Infants randomized to "late treatment" will receive blinded placebo. The criteria 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. Once hemodynamically significant PDA criteria met, if echo is positive, infants from both groups can receive open label ibuprofen; infants who had received placebo will be have ibuprofen for the first time (thus, "late" ibuprofen).

Late Ibuprofen expectant group

Drug: Late ibuprofen expectant group

IBUPROFEN DOSING SCHEDULE: At the diagnosis of PDA, infants randomized to "late ibuprofen expectant group" will receive blinded placebo. If criteria of a hemodynamically significant PDA develop, infants from this group can 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 + 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. Infants who had received placebo will be have ibuprofen for the first time (thus, "late" ibuprofen or expectant).

Other: Late ibuprofen expectant group

Other: Late Ibuprofen expectant group

Drug: Late ibuprofen expectant group

IBUPROFEN DOSING SCHEDULE: At the diagnosis of PDA, infants randomized to "late ibuprofen expectant group" will receive blinded placebo. If criteria of a hemodynamically significant PDA develop, infants from this group can 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 + 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. Infants who had received placebo will be have ibuprofen for the first time (thus, "late" ibuprofen or expectant).

Detailed Description:

Study terminated when 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

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

More Information

No publications provided

Responsible Party:	Ilene R.S. Sosenko, M.D., Division of Neonatology, University of Miami Miller School of Medicine
ClinicalTrials.gov Identifier:	NCT00802685 History of Changes
Other Study ID Numbers:	20070871
Study First Received:	December 4, 2008
Last Updated:	August 18, 2011
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
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 February 09, 2012