No Treatment Versus Oral Ibuprofen Treatment for Patent Ductus Arteriosus in Preterm Infants

Study Overview
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Brief Summary
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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
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This study is a randomized, double-blind, placebo-controlled, non-inferiority clinical trial.

Official Title
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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

Conditions
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Bronchopulmonary Dysplasia (BPD)

Intervention / Treatment
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* Drug: Oral ibuprofen
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: gestational age of 30 weeks or less or birth weight of 1250 g or less born in Samsung Medical Center confirmed to have hemodynamically significant patent ductus arteriosus (PDA) during day of life (DOL) 5 to 14 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

Ages Eligible for Study
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Minimum Age: 5 Days
Maximum Age: 14 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Oral ibuprofen<br>Initial dose of 10 mg/kg of oral ibuprofen, followed by 2 doses of 5 mg/kg 24 and 48 h later | Drug: Oral ibuprofen<br>* Initial dose of 10 mg/kg of oral ibuprofen, followed by two doses of 5 mg/kg 24 and 48 hours later<br>* Other names: Brufen® syrup, Samil pharm. Co., Ltd.;|
| Placebo Comparator: Normal saline<br>Initial dose of normal saline followed by second and third dose 24 and 48 hours later, at equal volume to ibuprofen arm | Drug: Normal saline<br>* Initial dose of normal saline followed by second and third dose 24 and 48 hours later, at equal volume to ibuprofen arm<br>* Other names: Sodium chloride, Huons. Inc.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of moderate to severe bronchopulmonary dysplasia (BPD) or mortality at 36 weeks postmenstrual age (PMA) |  | 36 weeks PMA | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of moderate to severe BPD |  | 36 weeks PMA | 
| Incidence of oxygen dependency at 40 weeks PMA |  | 40 weeks PMA | 
| Mortality rate |  | 28-days since birth and 36 weeks PMA | 
| incidence of intraventricular hemorrhage (grade 3 or greater) |  | 28-days since birth | 
| Incidence of retinopathy of prematurity (stage III or greater) |  | 40 weeks PMA (± 2 weeks) | 
| Incidence of necrotizing enterocolitis (stage 2b or greater) |  | 40 weeks PMA (± 2 weeks) | 
| Duration of PDA |  | 40 weeks PMA (± 2 weeks) | 
| Duration of intubation |  | 36 weeks PMA | 
| Duration of nasal continuous positive airway pressure (NCPAP) treatment |  | 40 weeks PMA (± 2 weeks) | 
| Cumulative duration of oxygen use |  | 40 weeks PMA (± 2 weeks) | 
| Incidence of adverse events |  | participants will be followed for the duration of hospital stay, an expected average of 12 weeks | 
| Growth velocity |  | 40 weeks PMA (± 2 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Patent ductus arteriosus, Ibuprofen, Bronchopulmonary dysplasia