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

NCT ID: NCT05493540

Last Updated: 2023-02-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-15
• Study Completion Date: 2022-09-01

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• Infants who are withdrawn from the study will be managed according to NICU Protocols.

Conditions

Patent Ductus Arteriosus After Premature Birth; Patent Ductus Arteriosus Conservative Management

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Medical treatment Group

40 preterm neonates will receive Ibuprofen oral suspension

Group Type: ACTIVE_COMPARATOR

Ibuprofen oral suspension

Intervention Type: DRUG

The medical treatment group will receive oral Ibuprofen with conservative therapy in the form of fluid restriction, Positive End Expiratory Pressure (PEEP), and/or diuretics

An additional course of Ibuprofen may be offered if there is:

1. Moderate/Severe PDA on Echocardiography

2. Prolonged ventilation or Increased ventilatory setting

3. Prolonged use of inotropes or vasopressors or escalating dose

• Another form of treatment may be offered if the patient developed side effects from Ibuprofen

Placebo Group

40 preterm neonates will receive oral placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo Group will receive Oral Placebo and Conservative therapy in the form of fluid restriction, PEEP, and/or diuretics

An Open-label option might be offered if there are concerns by attending physicians over the poor patient condition that might be attributed to persistent PDA:

1. Prolonged Ventilation or Escalating Ventilatory Setting

2. Prolonged Use Of Inotropes or Vasopressors or escalation of Doses

Rescue therapy in the form of a course of oral ibuprofen may be offered:

1. After 5 days of recruitment

2. Moderate/Severe PDA on Echocardiography

3. Prolonged ventilation or Increased ventilatory setting

4. Prolonged use of inotropes or vasopressors or escalating dose - Another form of treatment may be offered if the patient developed side effects from Ibuprofen

Interventions

Ibuprofen oral suspension

The medical treatment group will receive oral Ibuprofen with conservative therapy in the form of fluid restriction, Positive End Expiratory Pressure (PEEP), and/or diuretics

An additional course of Ibuprofen may be offered if there is:

1. Moderate/Severe PDA on Echocardiography

2. Prolonged ventilation or Increased ventilatory setting

3. Prolonged use of inotropes or vasopressors or escalating dose

• Another form of treatment may be offered if the patient developed side effects from Ibuprofen

Intervention Type: DRUG

Placebo

Placebo Group will receive Oral Placebo and Conservative therapy in the form of fluid restriction, PEEP, and/or diuretics

An Open-label option might be offered if there are concerns by attending physicians over the poor patient condition that might be attributed to persistent PDA:

1. Prolonged Ventilation or Escalating Ventilatory Setting

2. Prolonged Use Of Inotropes or Vasopressors or escalation of Doses

Rescue therapy in the form of a course of oral ibuprofen may be offered:

1. After 5 days of recruitment

2. Moderate/Severe PDA on Echocardiography

3. Prolonged ventilation or Increased ventilatory setting

4. Prolonged use of inotropes or vasopressors or escalating dose - Another form of treatment may be offered if the patient developed side effects from Ibuprofen

Intervention Type: DRUG

Other Intervention Names

Active treatment; Conservative

Eligibility Criteria

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

• Minimum Eligible Age: 1 Hour
• Maximum Eligible Age: 7 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nada Youssef

OTHER

Sponsor Role: lead

Responsible Party

Nada Youssef

Assistant lecturer of pediatrics and neonatology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Nada H Youssef

Role: PRINCIPAL_INVESTIGATOR

Ain Shams University

Locations

Faculty of Medicine Ain Shams University

Cairo, , Egypt

Countries

Egypt

Other Identifiers

MD 96 2020

Identifier Type: -

Identifier Source: org_study_id