Patent Ductus Arteriosus After Premature Birth, Patent Ductus Arteriosus Conservative Management
Conditions
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 * Infants who are withdrawn from the study will be managed according to NICU Protocols.
Interventions
DRUGIbuprofen 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
DRUGPlacebo
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
Sponsors
Nada Youssef
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
1 Hours to 7 Days
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 |
| 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 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 |
Countries
Egypt
Outcome results
None listed