Clinical trial NCT03860428: Early Treatment Versus Expectant Management of PDA in Preterm Infants
Official title: Randomized Non-inferiority Trial of Early Treatment Versus Expectant Management of Patent Ductus Arteriosus in Preterm Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Patent Ductus Arteriosus
Keywords: PDA
Ibuprofen
Paracetamol
Expectant management
Lead sponsor: Lviv National Medical University
Sponsor class: OTHER
First posted: 2019-03-04
Enrollment: 208
Sex: ALL
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of bronchopulmonary dysplasia (BPD) or mortality at 36 weeks postmenstrual age (PMA)
timeFrame: 36 weeks PMA
Secondary outcomes:
measure: PDA re-opening rate
timeFrame: Day 1 up to 3 month
measure: Closure rate of PDA within a week after the first and second course of pharmacological treatment
timeFrame: Participants will be evaluated at the end of first and second course, at an expected avarage of 10 days of life
measure: The need for surgical ductus closure
timeFrame: Day 1 up to 3 month
measure: Duration of any ventilation assist
timeFrame: Day 1 up to 3 month
measure: Duration of oxygen supplementation
timeFrame: Day 1 up to 3 month
measure: Age of administration of full volume of enteral nutrition
timeFrame: Day 1 up to 3 month
measure: Incidence of oliguria
timeFrame: In the first 14 days of life
measure: Incidence of hypotension
timeFrame: Day 1 up to 3 month
measure: Incidence of BPD
timeFrame: 36 weeks PMA
measure: Mortality rate
timeFrame: 36 weeks PMA
measure: Incidence of severe intraventricular hemorrhage
timeFrame: 28-days since birth
measure: Incidence of necrotizing enterocolitis (Bell stage ≥ IIa)
timeFrame: 36 weeks PMA
measure: Incidence of periventricular leukomalacia
timeFrame: 36 weeks PMA
Other outcomes:
Locations:
city: Lviv
country: Ukraine
facility: Lviv National Medical University
Study officials:
affiliation: L'viv National Medical University
name: Dmytro Dobryanskyy, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Potsiurko S, Dobryanskyy D, Sekretar L. Patent ductus arteriosus, systemic NT-proBNP concentrations and development of bronchopulmonary dysplasia in very preterm infants: retrospective data analysis from a randomized controlled trial. BMC Pediatr. 2021 Jun 19;21(1):286. doi: 10.1186/s12887-021-02750-9.