NCT03860428

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
208

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Feb 2019

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 15, 2019

Completed
1 day until next milestone

First Submitted

Initial submission to the registry

February 16, 2019

Completed
16 days until next milestone

First Posted

Study publicly available on registry

March 4, 2019

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 20, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 20, 2021

Completed
Last Updated

April 13, 2022

Status Verified

April 1, 2022

Enrollment Period

2.4 years

First QC Date

February 16, 2019

Last Update Submit

April 5, 2022

Conditions

Keywords

PDAIbuprofenParacetamolExpectant management

Outcome Measures

Primary Outcomes (1)

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

    36 weeks PMA

Secondary Outcomes (13)

  • PDA re-opening rate

    Day 1 up to 3 month

  • 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

  • Duration of oxygen supplementation

    Day 1 up to 3 month

  • +8 more secondary outcomes

Study Arms (3)

Rectal ibuprofen

ACTIVE COMPARATOR

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

Drug: Ibuprofen

Intravenous paracetamol

ACTIVE COMPARATOR

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

Drug: Paracetamol

Expectant Treatment

SHAM COMPARATOR

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.

Other: Expectant Management

Interventions

Expectative PDA management is character-ized as 'watchful waiting'. No intervention is initiated with the intention to close a PDA.

Also known as: Conservative management
Expectant Treatment

In the medical treatment arm the in-tention is to close the ductus arteriosus.

Also known as: Cyclooxygenase Inhibitor
Rectal ibuprofen

In the medical treatment arm the in-tention is to close the ductus arteriosus.

Also known as: Infulgan, Acetaminophen
Intravenous paracetamol

Eligibility Criteria

AgeUp to 3 Days
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Lviv National Medical University

Lviv, 79010, Ukraine

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Ductus Arteriosus, Patent

Interventions

IbuprofenCyclooxygenase InhibitorsAcetaminophenWatchful WaitingConservative Treatment

Condition Hierarchy (Ancestors)

Heart Defects, CongenitalCardiovascular AbnormalitiesCardiovascular DiseasesHeart DiseasesCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

PhenylpropionatesAcids, CarbocyclicCarboxylic AcidsOrganic ChemicalsEnzyme InhibitorsMolecular Mechanisms of Pharmacological ActionPharmacologic ActionsChemical Actions and UsesAnti-Inflammatory Agents, Non-SteroidalAnalgesics, Non-NarcoticAnalgesicsSensory System AgentsPeripheral Nervous System AgentsPhysiological Effects of DrugsAnti-Inflammatory AgentsTherapeutic UsesAntirheumatic AgentsAcetanilidesAnilidesAmidesAniline CompoundsAminesOutcome Assessment, Health CareOutcome and Process Assessment, Health CareQuality of Health CareHealth Services AdministrationTherapeutics

Study Officials

  • Dmytro Dobryanskyy, MD, PhD

    L'viv National Medical University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Clinical Professor

Study Record Dates

First Submitted

February 16, 2019

First Posted

March 4, 2019

Study Start

February 15, 2019

Primary Completion

July 20, 2021

Study Completion

July 20, 2021

Last Updated

April 13, 2022

Record last verified: 2022-04

Data Sharing

IPD Sharing
Will share

Locations