Timing of PDA Closure and Respiratory Outcome in Premature Infants

Patent Ductus Arteriosus Clinical Trial

Official title:

Timing of PDA Closure and Respiratory Outcome in Premature Infants

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00802685
• Other study ID #: 20070871
• Status: Terminated
• Phase: N/A
• First received: December 4, 2008
• Last updated: January 3, 2014
• Start date: November 2007
• Est. completion date: February 2011

Study information

• Verified date: December 2013
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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

Description:

Study terminated when intravenous (IV) ibuprofen withdrawn for both clinical and research use.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 105
• Est. completion date: February 2011
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 14 Days

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ductus Arteriosus, Patent
• Patent Ductus Arteriosus

Intervention

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.

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.

Locations

Country	Name	City	State
United States	Jackson Memorial Hospital/Holtz Children's Center	Miami	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of Miami	H. Lundbeck A/S

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Days Spent on Supplemental Oxygen During the First 28 Days.		28 days of life	No
Secondary	Number of Participants on Oxygen at 36 Weeks Postmenstrual Age		at 36 weeks postmenstrual age	No