Oral Ibuprofen Versus Placebo in Treatment of Patent Ductus Arteriosus (PDA)in Preterm Infants

Phase 2

Completed

• Conditions: Patent Ductus Arteriosus After Premature Birth; Patent Ductus Arteriosus Conservative Management
• Interventions: Drug: Ibuprofen oral suspension; Drug: Placebo

• Registration Number: NCT05493540
• Lead Sponsor: Nada Youssef

Brief Summary

The management options of Patent Ductus Arteriosus are still controversial and differ between centers. Recently, conservative management has been gaining interest as the evidence of benefit from medical treatment in terms of mortality and morbidity is lacking.

This study will compare oral ibuprofen (the standard treatment) with the conservative treatment, in terms of ductal closure and morbidity and mortality at discharge in preterm neonates less than 34 weeks.

Detailed Description

A double-blinded, randomized, placebo-control non-inferiority trial was conducted in the neonatal intensive care unit (NICU) of Ain Shams University children's hospital, Cairo, Egypt.

Informed consent was taken from the parents or legal guardians before enrolment, after fully explaining to them the nature of the study. The approval of the Research Ethics Committee at Ain Shams University was also obtained.

All preterm neonates less than 34 weeks were assessed in the first 48 hours by clinical and echocardiographic examination by a cardiologist to detect PDA and exclude any congenital heart disease.

All neonates meeting the inclusion criteria will be randomized into one of two groups:

Medical treatment group and Placebo group. Targeted neonatal Echo was repeated after 5 days of the start of medical treatment by a neonatologist or a cardiologist to assess PDA closure.

After 7 days of intervention, open-label is offered to all patients with the option of another course for patients in the medical treatment group and Rescue therapy in the Placebo group.

The short-term morbidity is documented.

Withdrawal and replacement of individual subjects:

* The attending physician can decide to withdraw a subject from the study for urgent medical reasons. If they wish, parents or caregivers can leave the study at any time for any reason.

* Infants who are withdrawn from the study will be managed according to NICU Protocols.

Study Timeline

• Study Start: 2021-04-15
• Study First Submitted: 2022-08-02
• Study First Submitted QC: 2022-08-07
• Study First Posted: 2022-08-09
• Primary Completion: 2022-08-15
• Study Completion: 2022-09-01
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-25
• Last Update Posted: 2023-02-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• Gestational age ≤ 34 weeks
• PDA Size > 1.5 mm and predominantly left-to-right shunt
• One of the following:
• Signs of Pulmonary overflow: Left atrium/Aortic diameter ratio (LA/Ao), Left Ventricular End Diastolic Diameter (LVEDD).
• Signs of Systemic Hypo perfusion: Absent or Reversed diastolic flow in the aorta, celiac/mesenteric, or Anterior Cerebral Artery (ACA)/ Middle Cerebral Artery (MCA)

Exclusion Criteria

• Chromosomal anomaly
• Congenital heart defect, other than PDA and/or patent foramen ovale
• Congenital or acquired gastrointestinal anomaly
• Previous episodes of Necrotizing enterocolitis (NEC) or intestinal perforation
• Active bleeding, especially intracranial or gastrointestinal hemorrhage
• Contraindications to the use of ibuprofen

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Medical treatment Group	Ibuprofen oral suspension	40 preterm neonates will receive Ibuprofen oral suspension
Placebo Group	Placebo	40 preterm neonates will receive oral placebo

Primary Outcome Measures

Name	Time	Method
Incidence of PDA Closure by Echocardiography	Hospital discharge (approximately 3 months unless death occurs first)	Compare the incidence of PDA closure assessed by Echocardiography during hospitalization between the two groups

Secondary Outcome Measures

Name	Time	Method
Incidence of Sepsis	Hospital discharge (approximately 3 months unless death occurs first)	Compare the Incidence of sepsis during hospitalization between the two groups by positive blood culture.
Incidence of Intraventricular hemorrhage (IVH)	Hospital discharge (approximately 3 months unless death occurs first)	Compare the Incidence of IVH during hospitalization between the two groups by transcranial ultrasound
Incidence of death during hospitalization	Hospital discharge (approximately 3 months unless death occurs first)	Compare the incidence of death during hospitalization between the two groups
Incidence of Bronchopulmonary dysplasia (BPD)	Hospital discharge (approximately 3 months unless death occurs first)	Compare the Incidence of BPD (needing supplemental oxygen at 28 days of life) during hospitalization between the two groups
Incidence of Necrotizing Enterocolitis (NEC)	Hospital discharge (approximately 3 months unless death occurs first)	Compare the incidence of NEC during hospitalization between the two groups by Bell's staging

Trial Locations

Locations (1)

Faculty of Medicine Ain Shams University; 🇪🇬 Cairo, Egypt