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Timing of PDA Closure and Respiratory Outcome in Premature Infants

Primary Purpose

Patent Ductus Arteriosus

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Early ibuprofen
Late ibuprofen expectant group (placebo)
Sponsored by
University of Miami
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Patent Ductus Arteriosus focused on measuring Patent ductus arteriosus, Respiratory outcome

Eligibility Criteria

1 Day - 14 Days (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Jackson Memorial Hospital/Holtz Children's Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

early ibuprofen

Late Ibuprofen expectant group (placebo)

Arm Description

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.

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).

Outcomes

Primary Outcome Measures

Days Spent on Supplemental Oxygen During the First 28 Days.

Secondary Outcome Measures

Number of Participants on Oxygen at 36 Weeks Postmenstrual Age

Full Information

First Posted
December 4, 2008
Last Updated
January 3, 2014
Sponsor
University of Miami
Collaborators
H. Lundbeck A/S
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1. Study Identification

Unique Protocol Identification Number
NCT00802685
Brief Title
Timing of PDA Closure and Respiratory Outcome in Premature Infants
Official Title
Timing of PDA Closure and Respiratory Outcome in Premature Infants
Study Type
Interventional

2. Study Status

Record Verification Date
December 2013
Overall Recruitment Status
Terminated
Why Stopped
Lack of availability of IV ibuprofen as of 8/10 due to a manufacturer's recall
Study Start Date
November 2007 (undefined)
Primary Completion Date
August 2010 (Actual)
Study Completion Date
February 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Miami
Collaborators
H. Lundbeck A/S

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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Study terminated when intravenous (IV) ibuprofen withdrawn for both clinical and research use.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Patent Ductus Arteriosus
Keywords
Patent ductus arteriosus, Respiratory outcome

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
105 (Actual)

8. Arms, Groups, and Interventions

Arm Title
early ibuprofen
Arm Type
Experimental
Arm Description
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.
Arm Title
Late Ibuprofen expectant group (placebo)
Arm Type
Other
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Early ibuprofen
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Late ibuprofen expectant group (placebo)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Days Spent on Supplemental Oxygen During the First 28 Days.
Time Frame
28 days of life
Secondary Outcome Measure Information:
Title
Number of Participants on Oxygen at 36 Weeks Postmenstrual Age
Time Frame
at 36 weeks postmenstrual age

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Day
Maximum Age & Unit of Time
14 Days
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ilene RS Sosenko, MD
Organizational Affiliation
University of Miami
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jackson Memorial Hospital/Holtz Children's Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22284563
Citation
Sosenko IR, Fajardo MF, Claure N, Bancalari E. Timing of patent ductus arteriosus treatment and respiratory outcome in premature infants: a double-blind randomized controlled trial. J Pediatr. 2012 Jun;160(6):929-35.e1. doi: 10.1016/j.jpeds.2011.12.031. Epub 2012 Jan 28.
Results Reference
derived

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Timing of PDA Closure and Respiratory Outcome in Premature Infants

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