Patent Ductus Arteriosus
Conditions
Keywords
PDA, Ibuprofen, Paracetamol, Expectant management
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.
Interventions
DRUGIbuprofen
In the medical treatment arm the in-tention is to close the ductus arteriosus.
DRUGParacetamol
In the medical treatment arm the in-tention is to close the ductus arteriosus.
OTHERExpectant Management
Expectative PDA management is character-ized as 'watchful waiting'. No intervention is initiated with the intention to close a PDA.
Sponsors
Lviv National Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 3 Days
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of bronchopulmonary dysplasia (BPD) or mortality at 36 weeks postmenstrual age (PMA) | 36 weeks PMA |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 |
| 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 | — |
| PDA re-opening rate | Day 1 up to 3 month | PDA re-opening after echocardiographically documented closure |
| Incidence of BPD | 36 weeks PMA | — |
| Mortality rate | 36 weeks PMA | — |
| Incidence of severe intraventricular hemorrhage | 28-days since birth | — |
| Incidence of necrotizing enterocolitis (Bell stage ≥ IIa) | 36 weeks PMA | — |
| Incidence of periventricular leukomalacia | 36 weeks PMA | — |
| Incidence of hypotension | Day 1 up to 3 month | — |
Countries
Ukraine
Outcome results
None listed