Early Treatment Versus Expectant Management of PDA in Preterm Infants

Not Applicable

Completed

• Conditions: Patent Ductus Arteriosus
• Interventions: Other: Expectant Management; Drug: Ibuprofen; Drug: Paracetamol

• Registration Number: NCT03860428
• Lead Sponsor: Lviv National Medical University

Brief Summary

Patent ductus arteriosus (PDA) in very preterm newborns is associated with severe neonatal mor-bidity: intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), necrotizing en-terocolitis (NEC), retinopathy of prematurity (ROP). Existing methods of management PDA do not reduce the incidence of these diseases. The efficacy of cyclooxygenase inhibitors (COX) which are currently the standard of treatment in extreme preterm infants is about 70-80%. COX inhibitors have significant side effects. On the other hand, surgical ligation of the ductus arteriosus is associated with deterioration due to cardio-pulmonary problems and long-term complications. Paracetamol has been proposed for treatment of hemodynamically significant PDA because it has a different mecha-nism of action compared with COX inhibitors and a better safety profile.

Recently, expectant approach has becoming more popular, although there is not enough evidence to support it.

The objective of this study is to investigate whether in preterm infants, born at a GA less than 32 weeks, with a PDA (diameter \> 1.5 mm) at a postnatal age of \< 72 h, an expectant management is non-inferior to early treatment with regard to the composite of mortality and/or severe morbidity.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-02-15
• Study First Submitted: 2019-02-16
• Study First Submitted QC: 2019-03-01
• Study First Posted: 2019-03-04
• Primary Completion: 2021-07-20
• Study Completion: 2021-07-20
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-05
• Last Update Posted: 2022-04-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 208

Inclusion Criteria

• Gestational age < 32 weeks
• Birthweight <1500 g
• Age less than 72 hours
• PDA diameter > 1.5 mm
• Signed informed consent obtained from both parents

Exclusion Criteria

• Birthweight ≥ 1500 g and/or gestation age ≥ 32 weeks
• Lack of informed consent of the parents
• Congenital heart defect, other than PDA and/or patent foramen ovale (PFO)
• The presence of a clinically apparent hemorrhagic syndrome
• Any intraventricular hemorrhage (IVH) in the first 48 hours or IVH grade 3-4
• A platelet count of < 50,000/mm3
• A serum creatinine concentration of > 110 μmol/L
• Oliguria <1 ml/kg/h
• Suspected/apparent NEC
• Suspected/apparent lung hypoplasia

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Expectant Treatment	Expectant Management	Expectant PDA management is characterized as 'watchful waiting'. No intervention is initiated with the intention to close a PDA unless defi-nitely needed based of the predefined infant's condition.
Rectal ibuprofen	Ibuprofen	Early treatment of PDA that starts within the first 3 days of life using rectal ibuprofen q24h for 3 days, dosages: 20 mg/kg + 10 mg/kg + 10 mg/kg
Intravenous paracetamol	Paracetamol	Early treatment of PDA that starts within the first 3 days of life using intravenous paraceta-mol 15 mg/kg q6h for 3 days

Primary Outcome Measures

Name	Time	Method
Incidence of bronchopulmonary dysplasia (BPD) or mortality at 36 weeks postmenstrual age (PMA)	36 weeks PMA

Secondary Outcome Measures

Name	Time	Method
Closure rate of PDA within a week after the first and second course of pharmacological treatment	Participants will be evaluated at the end of first and second course, at an expected avarage of 10 days of life
Mortality rate	36 weeks PMA
The need for surgical ductus closure	Day 1 up to 3 month
Duration of any ventilation assist	Day 1 up to 3 month	The ventilation assist time period
Incidence of necrotizing enterocolitis (Bell stage ≥ IIa)	36 weeks PMA
PDA re-opening rate	Day 1 up to 3 month	PDA re-opening after echocardiographically documented closure
Incidence of BPD	36 weeks PMA
Incidence of severe intraventricular hemorrhage	28-days since birth
Duration of oxygen supplementation	Day 1 up to 3 month	Days on supplement oxygen
Age of administration of full volume of enteral nutrition	Day 1 up to 3 month
Incidence of oliguria	In the first 14 days of life
Incidence of hypotension	Day 1 up to 3 month
Incidence of periventricular leukomalacia	36 weeks PMA

Trial Locations

Locations (1)

Lviv National Medical University; 🇺🇦 Lviv, Ukraine