Clinical trial NCT02128191: No Treatment Versus Oral Ibuprofen Treatment for Patent Ductus Arteriosus in Preterm Infants
Official title: Efficacy and Safety of No Treatment Compared With Oral Ibuprofen Treatment for Patent Ductus Arteriosus in Preterm Infants: a Randomized, Double-blind, Placebo-controlled, Non-inferiority Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bronchopulmonary Dysplasia (BPD)
Keywords: Patent ductus arteriosus
Ibuprofen
Bronchopulmonary dysplasia
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
First posted: 2014-05-01
Enrollment: 142
Sex: ALL
Minimum age (years): 5
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of no treatment compared with ibuprofen treatment for patent ductus arteriosus in preterm infants. The study hypothesis is that no treatment is not inferior to oral ibuprofen treatment in preterm infants. (non-inferiority study)

Detailed description: This study is a randomized, double-blind, placebo-controlled, non-inferiority clinical trial.

Eligibility criteria: Inclusion Criteria:

1. gestational age of 30 weeks or less or birth weight of 1250 g or less
2. born in Samsung Medical Center
3. confirmed to have hemodynamically significant patent ductus arteriosus (PDA) during day of life (DOL) 5 to 14
4. Definition of hemodynamically significant PDA: ductal size ≥ 1.5 mm with left-to-right shunt (or bidirectional shunt with dominant left-to-right blood flow) on the initial echocardiography plus at least one of clinical criteria.

   * Clinical criteria

     * Respiratory signs, including tachypnea, chest retraction, increased respiratory support, unable to wean respiratory support
     * Physical signs, including a murmur, hyperdynamic precordium or bounding pulses
     * Blood pressure problems, including decreased mean or diastolic pressure or increased pulse pressure
     * Signs of congestive heart failure, including cardiomegaly, hepatomegaly or pulmonary congestion

Exclusion Criteria:

* Mortality within the first 48 hours of life
* Ductal size \< 1.5 mm on the initial echocardiography
* Right-to-left shunt or bidirectional shunting with dominant right-to-left shunt through PDA
* congenital anomaly
* bilateral intraventricular hemorrhage of grade 4
* contraindication of ibuprofen (bleeding diasthesis, platelet count 10,000/mm3 or less, serum creatinine 2.0 mg/dL or greater, necrotizing enterocolitis stage 2 or greater

Primary outcomes:
measure: Incidence of moderate to severe bronchopulmonary dysplasia (BPD) or mortality at 36 weeks postmenstrual age (PMA)
timeFrame: 36 weeks PMA
Secondary outcomes:
measure: Incidence of moderate to severe BPD
timeFrame: 36 weeks PMA
measure: Incidence of oxygen dependency at 40 weeks PMA
timeFrame: 40 weeks PMA
measure: Mortality rate
timeFrame: 28-days since birth and 36 weeks PMA
measure: incidence of intraventricular hemorrhage (grade 3 or greater)
timeFrame: 28-days since birth
measure: Incidence of retinopathy of prematurity (stage III or greater)
timeFrame: 40 weeks PMA (± 2 weeks)
measure: Incidence of necrotizing enterocolitis (stage 2b or greater)
timeFrame: 40 weeks PMA (± 2 weeks)
measure: Duration of PDA
timeFrame: 40 weeks PMA (± 2 weeks)
measure: Duration of intubation
timeFrame: 36 weeks PMA
measure: Duration of nasal continuous positive airway pressure (NCPAP) treatment
timeFrame: 40 weeks PMA (± 2 weeks)
measure: Cumulative duration of oxygen use
timeFrame: 40 weeks PMA (± 2 weeks)
measure: Incidence of adverse events
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 12 weeks
measure: Growth velocity
timeFrame: 40 weeks PMA (± 2 weeks)
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Samsung Medical Center
name: Se In Sung, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sung SI, Lee MH, Ahn SY, Chang YS, Park WS. Effect of Nonintervention vs Oral Ibuprofen in Patent Ductus Arteriosus in Preterm Infants: A Randomized Clinical Trial. JAMA Pediatr. 2020 Aug 1;174(8):755-763. doi: 10.1001/jamapediatrics.2020.1447.