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Early Treatment Versus Expectant Management of PDA in Preterm Infants

Primary Purpose

Patent Ductus Arteriosus

Status
Completed
Phase
Not Applicable
Locations
Ukraine
Study Type
Interventional
Intervention
Ibuprofen
Paracetamol
Expectant Management
Sponsored by
Lviv National Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Patent Ductus Arteriosus focused on measuring PDA, Ibuprofen, Paracetamol, Expectant management

Eligibility Criteria

undefined - 3 Days (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Lviv National Medical University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Sham Comparator

Arm Label

Rectal ibuprofen

Intravenous paracetamol

Expectant Treatment

Arm Description

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

Early treatment of PDA that starts within the first 3 days of life using intravenous paraceta-mol 15 mg/kg q6h for 3 days

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

PDA re-opening rate
PDA re-opening after echocardiographically documented closure
Closure rate of PDA within a week after the first and second course of pharmacological treatment
The need for surgical ductus closure
Duration of any ventilation assist
The ventilation assist time period
Duration of oxygen supplementation
Days on supplement oxygen
Age of administration of full volume of enteral nutrition
Incidence of oliguria
Incidence of hypotension
Incidence of BPD
Mortality rate
Incidence of severe intraventricular hemorrhage
Incidence of necrotizing enterocolitis (Bell stage ≥ IIa)
Incidence of periventricular leukomalacia

Full Information

First Posted
February 16, 2019
Last Updated
April 5, 2022
Sponsor
Lviv National Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT03860428
Brief Title
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

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
February 15, 2019 (Actual)
Primary Completion Date
July 20, 2021 (Actual)
Study Completion Date
July 20, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Lviv National Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Patent Ductus Arteriosus
Keywords
PDA, Ibuprofen, Paracetamol, Expectant management

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
208 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rectal ibuprofen
Arm Type
Active Comparator
Arm Description
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
Arm Title
Intravenous paracetamol
Arm Type
Active Comparator
Arm Description
Early treatment of PDA that starts within the first 3 days of life using intravenous paraceta-mol 15 mg/kg q6h for 3 days
Arm Title
Expectant Treatment
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ibuprofen
Other Intervention Name(s)
Cyclooxygenase Inhibitor
Intervention Description
In the medical treatment arm the in-tention is to close the ductus arteriosus.
Intervention Type
Drug
Intervention Name(s)
Paracetamol
Other Intervention Name(s)
Infulgan, Acetaminophen
Intervention Description
In the medical treatment arm the in-tention is to close the ductus arteriosus.
Intervention Type
Other
Intervention Name(s)
Expectant Management
Other Intervention Name(s)
Conservative management
Intervention Description
Expectative PDA management is character-ized as 'watchful waiting'. No intervention is initiated with the intention to close a PDA.
Primary Outcome Measure Information:
Title
Incidence of bronchopulmonary dysplasia (BPD) or mortality at 36 weeks postmenstrual age (PMA)
Time Frame
36 weeks PMA
Secondary Outcome Measure Information:
Title
PDA re-opening rate
Description
PDA re-opening after echocardiographically documented closure
Time Frame
Day 1 up to 3 month
Title
Closure rate of PDA within a week after the first and second course of pharmacological treatment
Time Frame
Participants will be evaluated at the end of first and second course, at an expected avarage of 10 days of life
Title
The need for surgical ductus closure
Time Frame
Day 1 up to 3 month
Title
Duration of any ventilation assist
Description
The ventilation assist time period
Time Frame
Day 1 up to 3 month
Title
Duration of oxygen supplementation
Description
Days on supplement oxygen
Time Frame
Day 1 up to 3 month
Title
Age of administration of full volume of enteral nutrition
Time Frame
Day 1 up to 3 month
Title
Incidence of oliguria
Time Frame
In the first 14 days of life
Title
Incidence of hypotension
Time Frame
Day 1 up to 3 month
Title
Incidence of BPD
Time Frame
36 weeks PMA
Title
Mortality rate
Time Frame
36 weeks PMA
Title
Incidence of severe intraventricular hemorrhage
Time Frame
28-days since birth
Title
Incidence of necrotizing enterocolitis (Bell stage ≥ IIa)
Time Frame
36 weeks PMA
Title
Incidence of periventricular leukomalacia
Time Frame
36 weeks PMA

10. Eligibility

Sex
All
Maximum Age & Unit of Time
3 Days
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dmytro Dobryanskyy, MD, PhD
Organizational Affiliation
L'viv National Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lviv National Medical University
City
Lviv
ZIP/Postal Code
79010
Country
Ukraine

12. IPD Sharing Statement

Plan to Share IPD
Yes
Citations:
PubMed Identifier
34147090
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.
Results Reference
derived

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Early Treatment Versus Expectant Management of PDA in Preterm Infants

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