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Early Treatment Versus Expectant Management of PDA in Preterm Infants

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ClinicalTrials.gov Identifier: NCT03860428
Recruitment Status : Recruiting
First Posted : March 4, 2019
Last Update Posted : March 4, 2019
Sponsor:
Information provided by (Responsible Party):
Dmytro Dobryanskyy, 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.


Condition or disease Intervention/treatment Phase
Patent Ductus Arteriosus Drug: Ibuprofen Drug: Paracetamol Other: Expectant Management Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 168 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Non-inferiority Trial of Early Treatment Versus Expectant Management of Patent Ductus Arteriosus in Preterm Infants
Actual Study Start Date : February 15, 2019
Estimated Primary Completion Date : January 10, 2022
Estimated Study Completion Date : April 10, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Ibuprofen

Arm Intervention/treatment
Active Comparator: Rectal 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
Drug: Ibuprofen
In the medical treatment arm the in-tention is to close the ductus arteriosus.
Other Name: Cyclooxygenase Inhibitor

Active Comparator: Intravenous 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
Drug: Paracetamol
In the medical treatment arm the in-tention is to close the ductus arteriosus.
Other Name: Infulgan, Acetaminophen

Sham Comparator: Expectant Treatment
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
Expectative PDA management is character-ized as 'watchful waiting'. No intervention is initiated with the intention to close a PDA.
Other Name: Conservative management




Primary Outcome Measures :
  1. Composite of mortality, and/or NEC, and/or IVH, and/or periventricular leukomalacia (PVL), and/or BPD [ Time Frame: At a postmenstrual age of 36 completed weeks ]
    The primary outcome is the composite of mortality, and/or NEC (Bell stage ≥ IIa), and/or severe IVH, and/or PVL, and/or BPD, defined as the need for supplemental oxygen need, all at a postmenstrual age of 36 completed weeks.

  2. Failure to close the duct 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 8 days of life ]
    The rate of failures closing the duct after the first and second course of the specific therapy with rectal ibuprofen and intravenous paracetamol.


Secondary Outcome Measures :
  1. Mortality [ Time Frame: 28 days and before a postmenstrual age of 36 completed weeks ]
    The incidence of death for the first 28 days and before a postmenstrual age of 36 completed weeks

  2. Incidence of BPD [ Time Frame: Day 1 up to a postmenstrual age of 36 completed weeks ]
  3. Severe morbidity [ Time Frame: Day 1 up to a postmenstrual age of 36 completed weeks or discharge ]
    The incidence of IVH, severe IVH, PVL, NEC [Bell stage ≥ IIa], ROP, sepsis, pulmonary air leakage (e.g. pneumothorax); pulmonary hemorrhage, gastrointestinal bleeding, extrauterine growth retardation

  4. PDA re-opening rate [ Time Frame: Day 1 up to 3 month ]
    PDA re-opening after echocardiographically documented closure

  5. The need for surgical ductus closure [ Time Frame: Day 1 up to 3 month ]
    The rate of surgical ligation

  6. Incidence of hypotension [ Time Frame: Day 1 up to 3 month ]
  7. Short term sequelae of cardiovascular failure [ Time Frame: Day 1 up to 3 month ]
    At the time of discharge the incidence of cardiovascular failure is calculated

  8. Duration of any ventilation assist [ Time Frame: Day 1 up to 3 month ]
    The ventilation assist time period

  9. Total days of oxygen supplementation [ Time Frame: Day 1 up to 3 month ]
    Days on supplement oxygen

  10. Age of administration of full volume of enteral nutrition [ Time Frame: Day 1 up to 3 month ]
    Day till the infant reaches 120 kcal/kg/d

  11. Incidence of oliguria [ Time Frame: In the first 14 days of life ]
    Rate of oliguria defined as a reduction on urine output less than 1ml/Kg/h,



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Ages Eligible for Study:   up to 3 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03860428


Contacts
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Contact: Dmytro Dobryanskyy, MD, PhD +380672535757 dmytro_d@hotmail.com

Locations
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Ukraine
Lviv National Medical University Recruiting
Lviv, Ukraine, 79010
Contact: Dmytro Dobryanskyy, MD, PhD    +380672535757    dmytro_d@hotmail.com   
Contact: Solomiya Yaremchuk, MD    +380685435629    solyayaremchuk4@gmail.com   
Sponsors and Collaborators
Lviv National Medical University
Investigators
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Principal Investigator: Dmytro Dobryanskyy, MD, PhD L'viv National Medical University

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Responsible Party: Dmytro Dobryanskyy, Clinical Professor, Lviv National Medical University
ClinicalTrials.gov Identifier: NCT03860428    
Other Study ID Numbers: 04011994
First Posted: March 4, 2019    Key Record Dates
Last Update Posted: March 4, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dmytro Dobryanskyy, Lviv National Medical University:
PDA
Ibuprofen
Paracetamol
Expectant management
Additional relevant MeSH terms:
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Ductus Arteriosus, Patent
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities
Acetaminophen
Ibuprofen
Cyclooxygenase Inhibitors
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antipyretics
Anti-Inflammatory Agents, Non-Steroidal
Anti-Inflammatory Agents
Antirheumatic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action