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Paracetamol And Ibuprofen in Closing Patent Ductus Arteriosus (PAI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03648437
Recruitment Status : Recruiting
First Posted : August 27, 2018
Last Update Posted : January 10, 2019
Sponsor:
Information provided by (Responsible Party):
Outi Aikio, University of Oulu

Brief Summary:
The purpose of this pilot trial is to study efficacy and safety of simultaneous intravenous (iv) ibuprofen and paracetamol medications in the closure of patent ductus arteriosus (PDA) in preterm infants. It is randomized, placebo-controlled, double-blind, phase 1, one center, clinical trial, with an additional open arm.

Condition or disease Intervention/treatment Phase
Patent Ductus Arteriosus Drug: Paracetamol 10Mg/mL Drug: 0.45% Sodium Chloride Drug: Ibuprofen Phase 1

Detailed Description:

Premature infants (born before 37 weeks gestational age) with paptent ductus arteriosus (PDA) are the focus of the study since no trials on the additive efficacy of these two medications on the contraction of ductus arteriosus are available. Preterm infants who are diagnosed to have a hemodynamically significant PDA and who, according to the decision of the attending clinician, need ibuprofen therapy, are eligible to this trial.

If the parents deny the consent for randomization, they are asked for the permission to use the patient data of the child for research purposes. If this permission is given, these patients form the additional open arm of the study.

If the parents deny the consent, the patient will be treated according to the standard PDA treatment of Oulu University Hospital: three days' iv ibuprofen Pedea® 5mg/ml solution infusion, dosing: 10 mg/kg + 5 mg/kg + 5 mg/kg (q24h). In case of any contraindications for ibuprofen, the treatment would be surgical ligation.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: one center, randomized, placebo-controlled, double-blind, clinical trial with an additional open arm
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Placebo, 0.45 % saline, is similar to paracetamol, both being clear liquids, so the staff will remain unaware which drug the patient receives. The study drug will be kept and prepared away from the neonatal intensive care unit, at the separate ward 55 office, in a locked cabinet. The study drug will be prepared by the research nurse, the pharmacist of the ward, or during nighttime, by a nurse who does not participate in the study patients' treatment in any way.
Primary Purpose: Treatment
Official Title: Paracetamol And Ibuprofen in Closing Patent Ductus Arteriosus
Actual Study Start Date : September 3, 2018
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : March 2021


Arm Intervention/treatment
Experimental: Pedea 5mg/mL and Paracetamol 10Mg/mL
Intravenous (IV) ibuprofen 5mg/mL q 24h for 3 days, dosages: 10mg/kg + 5mg/kg + 5mg/kg and IV paracetamol 10mg/mL for 3 days: loading dose 20mg/kg, following 7.5mg/kg q 6h (up to12 doses)
Drug: Paracetamol 10Mg/mL
Experimental drug
Other Name: Paracetamol Fresenius Kabi 10mg/mL infusion solution

Drug: Ibuprofen
Standard therapy
Other Name: Pedea 5mg/mL injection solution

Placebo Comparator: Pedea 5mg/mL and 0.45 sodium chloride
IV ibuprofen 5mg/mL q 24h for 3 days, dosages: 10mg/kg + 5mg/kg + 5mg/kg and NaCl 0.45% for 3 days, the same amount in mL as would have been given IV paracetamol
Drug: 0.45% Sodium Chloride
Placebo comparator
Other Name: NATRIUMKLORID BRAUN 4,5 mg/ml infusion solution

Drug: Ibuprofen
Standard therapy
Other Name: Pedea 5mg/mL injection solution

Pedea 5mg/mL, open arm
Intravenous (IV) ibuprofen 5mg/mL q 24h for 3 days, dosages: 10mg/kg + 5mg/kg + 5mg/kg, open arm
Drug: Ibuprofen
Standard therapy
Other Name: Pedea 5mg/mL injection solution




Primary Outcome Measures :
  1. Ductal closure [ Time Frame: Neonatal internsive care unit (NICU) stay up to 12 weeks ]
    Number of patients with ductal contraction without need for other PDA therapies


Secondary Outcome Measures :
  1. Need for ductal therapies [ Time Frame: NICU stay up to 12 weeks ]
    Given ductal therapies after the study drug

  2. Cardiac ultrasound findings [ Time Frame: NICU stay up to 12 weeks ]
    Ductal caliber (mm, mm/kg), LA/Ao ratio

  3. Duration of any ventilation assist [ Time Frame: NICU stay up to 12 weeks ]
    The ventilation assist time pediod

  4. Paracetamol serum levels [ Time Frame: Study drug period up to 4 days ]
    Measured paracetamol concentrations (mg/mL)

  5. Paracetamol side effects [ Time Frame: Study drug period plus 7 days, up to 10 days ]
    Observed adverse events linked to study drug

  6. Long term complications of prematurity [ Time Frame: Hospital stay up to 18 weeks ]
    Moderate-to-severe bronchopulmonary dysplasia, intraventricular hemorrhage grade 2-4, moderate to severe necrotizing enterocolitis, retinopathy of prematurity needing therapy

  7. Other long-term morbidity, and mortality [ Time Frame: Hospital stay up to 18 weeks ]
    Other severe diseases



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 4 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Preterm infants (born before 37+0 gestation weeks) who are diagnosed to have a hemodynamically significant PDA and who, according to the decision of the attending clinician, need ibuprofen therapy, are eligible to this trial.

Exclusion Criteria:

  • severe malformation or suspected chromosomal defect
  • other very severe life-threatening disease (e.g. very severe birth asphyxia or persistent pulmonary hypertension, etc.)

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): NCT03648437


Contacts
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Contact: Outi Aikio, MD, PhD +35883155810 outi.aikio@ppshp.fi
Contact: Aliisa Laitala, MD +35883155823 aliisa.laitala@ppshp.fi

Locations
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Finland
Department of Pediatrics, Oulu University Hospital Recruiting
Oulu, Finland, 90014
Contact: Outi Aikio, MD, PhD    +358 8 3155810    outi.aikio@ppshp.fi   
Principal Investigator: Outi Aikio, MD, PhD         
Principal Investigator: Antti Harma, MD         
Principal Investigator: Timo Saarela, MD, PhD         
Principal Investigator: Mikko Hallman, MD, PhD         
Principal Investigator: Aliisa Laitala, MD         
Sponsors and Collaborators
University of Oulu
Investigators
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Principal Investigator: Outi Aikio, MD, PhD Oulu Univerisity Hospital
  Study Documents (Full-Text)

Documents provided by Outi Aikio, University of Oulu:

Publications:
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Responsible Party: Outi Aikio, MD, PhD, Specialist in Peditrics and Neonatology, University of Oulu
ClinicalTrials.gov Identifier: NCT03648437    
Other Study ID Numbers: 38/2018
First Posted: August 27, 2018    Key Record Dates
Last Update Posted: January 10, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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 Outi Aikio, University of Oulu:
acetaminophen
ibuprofen
preterm infant
near infra-red spectroscopy
Additional relevant MeSH terms:
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Ductus Arteriosus, Patent
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities
Acetaminophen
Ibuprofen
Pharmaceutical Solutions
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antipyretics