Trial Outcomes & Findings for Timing of PDA Closure and Respiratory Outcome in Premature Infants (NCT NCT00802685)

NCT ID: NCT00802685

Last Updated: 2014-02-05

Results Overview

• Recruitment status: TERMINATED
• Study phase: NA
• Target enrollment: 105 participants
• Primary outcome timeframe: 28 days of life
• Results posted on: 2014-02-05

Participant Flow

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.

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 Of these, 6 consents were withdrawn and 68 enrolled subjects were not randomized because they met exclusion criterion before randomization: hemodynamically significant PDA (n=10), absence of PDA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

Participant milestones

Measure	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
Overall Study STARTED	54	51
Overall Study COMPLETED	54	51
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Timing of PDA Closure and Respiratory Outcome in Premature Infants

Baseline characteristics by cohort

Measure	Early Ibuprofen n=54 Participants 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 n=51 Participants 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 n=105 Participants Total of all reporting groups
Age, Categorical <=18 years	54 Participants n=93 Participants	51 Participants n=4 Participants	105 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Sex: Female, Male Female	29 Participants n=93 Participants	21 Participants n=4 Participants	50 Participants n=27 Participants
Sex: Female, Male Male	25 Participants n=93 Participants	30 Participants n=4 Participants	55 Participants n=27 Participants
Region of Enrollment United States	54 participants n=93 Participants	51 participants n=4 Participants	105 participants n=27 Participants

PRIMARY outcome

Timeframe: 28 days of life

Population: The number of participants for analysis was determined from all subjects who completed the study intervention at 28 days of age and had complete data on the primary endpoint of oxygen days during the first 28 days. Analysis was done on intention to treat basis.

Outcome measures

Measure	Early Ibuprofen n=54 Participants 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 n=51 Participants 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
Days Spent on Supplemental Oxygen During the First 28 Days.	21 days Interval 7.0 to 27.0	19 days Interval 5.0 to 26.0

SECONDARY outcome

Timeframe: at 36 weeks postmenstrual age

Outcome measures

Measure	Early Ibuprofen n=54 Participants 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 n=51 Participants 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
Number of Participants on Oxygen at 36 Weeks Postmenstrual Age	17 participants Interval 15.0 to 20.0	16 participants Interval 15.0 to 20.0

Adverse Events

Early Ibuprofen

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Late Ibuprofen Expectant Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Ilene R. S. Sosenko, M.D.

University of Miami

Phone: 305-585-6408

Email: isosenko@miami.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place