Oral Ibuprofen Versus Placebo in Treatment of Patent Ductus Arteriosus (PDA)in Preterm Infants
Primary Purpose
Patent Ductus Arteriosus After Premature Birth, Patent Ductus Arteriosus Conservative Management
Status
Completed
Phase
Phase 2
Locations
Egypt
Study Type
Interventional
Intervention
Ibuprofen oral suspension
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Patent Ductus Arteriosus After Premature Birth
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
Sites / Locations
- Faculty of Medicine Ain Shams University
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Medical treatment Group
Placebo Group
Arm Description
40 preterm neonates will receive Ibuprofen oral suspension
40 preterm neonates will receive oral placebo
Outcomes
Primary Outcome Measures
Incidence of PDA Closure by Echocardiography
Compare the incidence of PDA closure assessed by Echocardiography during hospitalization between the two groups
Secondary Outcome Measures
Incidence of death during hospitalization
Compare the incidence of death during hospitalization between the two groups
Incidence of Necrotizing Enterocolitis (NEC)
Compare the incidence of NEC during hospitalization between the two groups by Bell's staging
Incidence of Bronchopulmonary dysplasia (BPD)
Compare the Incidence of BPD (needing supplemental oxygen at 28 days of life) during hospitalization between the two groups
Incidence of Sepsis
Compare the Incidence of sepsis during hospitalization between the two groups by positive blood culture.
Incidence of Intraventricular hemorrhage (IVH)
Compare the Incidence of IVH during hospitalization between the two groups by transcranial ultrasound
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05493540
Brief Title
Oral Ibuprofen Versus Placebo in Treatment of Patent Ductus Arteriosus (PDA)in Preterm Infants
Official Title
Oral Ibuprofen Versus Placebo in Management of Patent Ductus Arteriosus in Preterm Infants: A Double Blind, Randomized Control Trial
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
April 15, 2021 (Actual)
Primary Completion Date
August 15, 2022 (Actual)
Study Completion Date
September 1, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Nada Youssef
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Patent Ductus Arteriosus After Premature Birth, Patent Ductus Arteriosus Conservative Management
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
80 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Medical treatment Group
Arm Type
Active Comparator
Arm Description
40 preterm neonates will receive Ibuprofen oral suspension
Arm Title
Placebo Group
Arm Type
Placebo Comparator
Arm Description
40 preterm neonates will receive oral placebo
Intervention Type
Drug
Intervention Name(s)
Ibuprofen oral suspension
Other Intervention Name(s)
Active treatment
Intervention Description
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:
Moderate/Severe PDA on Echocardiography
Prolonged ventilation or Increased ventilatory setting
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
Intervention Name(s)
Placebo
Other Intervention Name(s)
Conservative
Intervention Description
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:
Prolonged Ventilation or Escalating Ventilatory Setting
Prolonged Use Of Inotropes or Vasopressors or escalation of Doses
Rescue therapy in the form of a course of oral ibuprofen may be offered:
After 5 days of recruitment
Moderate/Severe PDA on Echocardiography
Prolonged ventilation or Increased ventilatory setting
Prolonged use of inotropes or vasopressors or escalating dose - Another form of treatment may be offered if the patient developed side effects from Ibuprofen
Primary Outcome Measure Information:
Title
Incidence of PDA Closure by Echocardiography
Description
Compare the incidence of PDA closure assessed by Echocardiography during hospitalization between the two groups
Time Frame
Hospital discharge (approximately 3 months unless death occurs first)
Secondary Outcome Measure Information:
Title
Incidence of death during hospitalization
Description
Compare the incidence of death during hospitalization between the two groups
Time Frame
Hospital discharge (approximately 3 months unless death occurs first)
Title
Incidence of Necrotizing Enterocolitis (NEC)
Description
Compare the incidence of NEC during hospitalization between the two groups by Bell's staging
Time Frame
Hospital discharge (approximately 3 months unless death occurs first)
Title
Incidence of Bronchopulmonary dysplasia (BPD)
Description
Compare the Incidence of BPD (needing supplemental oxygen at 28 days of life) during hospitalization between the two groups
Time Frame
Hospital discharge (approximately 3 months unless death occurs first)
Title
Incidence of Sepsis
Description
Compare the Incidence of sepsis during hospitalization between the two groups by positive blood culture.
Time Frame
Hospital discharge (approximately 3 months unless death occurs first)
Title
Incidence of Intraventricular hemorrhage (IVH)
Description
Compare the Incidence of IVH during hospitalization between the two groups by transcranial ultrasound
Time Frame
Hospital discharge (approximately 3 months unless death occurs first)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Hour
Maximum Age & Unit of Time
7 Days
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nada H Youssef
Organizational Affiliation
Ain Shams University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Faculty of Medicine Ain Shams University
City
Cairo
Country
Egypt
12. IPD Sharing Statement
Learn more about this trial
Oral Ibuprofen Versus Placebo in Treatment of Patent Ductus Arteriosus (PDA)in Preterm Infants
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