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
Results First Received: June 17, 2013  
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
Condition: Patent Ductus Arteriosus
Interventions: Drug: Early ibuprofen
Other: Late ibuprofen expectant group (placebo)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruitment was initiated on 01/02/08; the final patient was recruited on 7/26/10. Patients were enrolled at Jackson Memorial Hospital. Study was terminated early due to lack of availability of IV ibuprofen due to manufacturer's recall.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

179 subjects had consents obtained. Of these, 6 consents were withdrawn and 68 enrolled subjects were not randomized because they met exclusion criterion before randomization: hemodynamically significant PDA (n=10), absence of PDA (n=55) and other reasons (n=3).

Therefore 105 enrolled subjects were randomized into 1 of 2 treatment arms.


Reporting Groups
  Description
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.

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" w

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).

Late ibuprofen expectant group : Other: Late Ibuprofen expectant


Participant Flow:   Overall Study
    Early Ibuprofen     Late Ibuprofen Expectant Group  
STARTED     54     51  
COMPLETED     54     51  
NOT COMPLETED     0     0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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.

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" w

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).

Late ibuprofen expectant group : Other: Late Ibuprofen expectant

Total Total of all reporting groups

Baseline Measures
    Early Ibuprofen     Late Ibuprofen Expectant Group     Total  
Number of Participants  
[units: participants]
  54     51     105  
Age  
[units: participants]
     
<=18 years     54     51     105  
Between 18 and 65 years     0     0     0  
>=65 years     0     0     0  
Gender  
[units: participants]
     
Female     29     21     50  
Male     25     30     55  
Region of Enrollment  
[units: participants]
     
United States     54     51     105  



  Outcome Measures
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1.  Primary:   Days Spent on Supplemental Oxygen During the First 28 Days.   [ Time Frame: 28 days of life ]

2.  Secondary:   Number of Participants on Oxygen at 36 Weeks Postmenstrual Age   [ Time Frame: at 36 weeks postmenstrual age ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Ilene R. S. Sosenko, M.D.
Organization: University of Miami
phone: 305-585-6408
e-mail: isosenko@miami.edu


No publications provided by University of Miami

Publications automatically indexed to this study:

Responsible Party: Ilene R.S. Sosenko, M.D., 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