NCT07533721

Ibuprofen vs Expectant Management for hsPDA in Preterm Infants: Retrospective Cohort

Individualized Management Over Routine Intervention: Evidence Against Early Ibuprofen for PDA From Combined Retrospective and Meta-Analytic Data

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 541 (actual)
• Sponsor: Shengjing Hospital · Academic / Other
• Sex: All
• Age: 23 Weeks – 37 Weeks
• Healthy volunteers: Not accepted

Summary

This retrospective cohort study compares ibuprofen treatment versus expectant management for hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. Data were collected from preterm infants with hsPDA admitted to the Department of Neonatology, Shengjing Hospital of China Medical University between June 2020 and June 2025. A total of 541 infants were included: 241 received ibuprofen and 300 received expectant management (no routine pharmacological closure, supportive care only). The primary outcome is PDA closure rate. Secondary outcomes include bronchopulmonary dysplasia (BPD), mortality, pulmonary hypertension, renal insufficiency, neonatal pneumonia, retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), pulmonary hemorrhage, and gastrointestinal bleeding. Analyses are stratified by gestational age (\<28 weeks, 28-33 weeks, 33-37 weeks) and adjusted for sex, multiple gestation, and maternal factors. The study aims to provide real-world evidence on the risks and benefits of ibuprofen closure in different gestational age subgroups.

Detailed description

Background: Patent ductus arteriosus (PDA) is common in preterm infants. When hemodynamically significant (hsPDA), it may lead to pulmonary overcirculation, systemic hypoperfusion, and increased risk of bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and other neonatal morbidities. Pharmacological closure with cyclooxygenase inhibitors such as ibuprofen is often used, but the benefits of routine closure remain controversial, particularly across different gestational age groups. Expectant management (allowing spontaneous closure without drugs) has gained interest, but comparative data are limited. Objectives: To compare ibuprofen versus expectant management for PDA closure and neonatal outcomes in preterm infants with hsPDA. To examine effect modification by gestational age (\<28 weeks, 28-33 weeks, 33-37 weeks). To explore associations with sex, multiple gestation, and maternal factors. Study design: Single-center retrospective cohort study. Setting: Department of Neonatology, Shengjing Hospital of China Medical University, Shenyang, China. Participants: Preterm infants with echocardiographically confirmed hsPDA born between June 2020 and June 2025. Exclusion criteria: major congenital anomalies, chromosomal disorders, congenital heart disease other than PDA, contraindications to ibuprofen (e.g., renal failure, necrotizing enterocolitis), missing outcome data, or prior receipt of other PDA pharmacotherapy. Intervention: Ibuprofen (oral or intravenous) at standard neonatal dosing (typically 10-5-5 mg/kg). Timing and duration as per clinical protocol. Comparator: Expectant management - no routine pharmacological closure, allowing fluid restriction, diuretics, or supportive care alone. Outcomes: Primary: PDA closure (confirmed by echocardiography). Secondary: BPD, mortality (all causes), pulmonary hypertension, renal insufficiency, neonatal pneumonia, ROP (any stage), IVH (any grade), pulmonary hemorrhage, gastrointestinal bleeding. Data sources: Electronic medical records of Shengjing Hospital. Statistical analysis:Descriptive statistics: frequencies, means (SD) or medians (IQR). Bivariate comparisons: chi-square or Fisher's exact test for categorical variables; t-test or Mann-Whitney U test for continuous variables. Multivariable logistic regression to estimate adjusted risk ratios (RR) and 95% confidence intervals for outcomes, adjusting for gestational age, sex, multiple gestation, and maternal factors (e.g., preeclampsia, chorioamnionitis). Stratified analyses by gestational age subgroups. Sensitivity analyses: excluding infants with protocol deviations or incomplete follow-up. Ethical approval: Obtained from the Clinical Research Ethics Committee of Shengjing Hospital of China Medical University (approval number to be inserted). The study adheres to the Declaration of Helsinki. Limitations: Single-center design, potential selection bias, residual confounding despite multivariable adjustment. Results may not be generalizable to other settings. Dissemination: Results will be submitted for publication in a peer-reviewed journal.

Conditions

• Patent Ductus Arteriosus
• Infant, Premature

Interventions

Type	Name	Description
DRUG	Ibuprofen	No routine pharmacological closure; fluid restriction, diuretics, or supportive care only.

Timeline

• Start date: 2020-06-01
• Primary completion: 2025-06-30
• Completion: 2025-06-30
• First posted: 2026-04-16
• Last updated: 2026-04-16

Locations

1 site across 1 country: China