Paracetamol And Ibuprofen/Indomethacin in Closing Patent Ductus Arteriosus (PAI)

October 16, 2024 updated by: Outi Aikio, University of Oulu

Paracetamol And Ibuprofen/Indomethacin in Closing Patent Ductus Arteriosus of Preterm Infants - Randomised, Placebo-controlled Multicentre Trial

The purpose of this pilot trial is to study efficacy and safety of simultaneous intravenous (iv) ibuprofen/indomethacin and paracetamol medications in the closure of patent ductus arteriosus (PDA) in preterm infants. It is randomized, placebo-controlled, double-blind, phase 1, multicenter, clinical trial.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Premature infants (born before 37 weeks gestational age) with patent 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/indomethacin therapy, are eligible to this trial.

If the parents deny the consent, the patient will be treated according to the standard PDA treatment: three days' iv ibuprofen Pedea® 5mg/ml solution infusion (Oulu, Helsinki, Tartu) dosing: 10mg/kg + 5mg/kg + 5mg/kg (q24h); or three days' iv indomethacin (Turku) 0.2mg/kg + 0.1mg/kg + 0.1mg/kg (q24h). In case of any contraindications for ibuprofen/indomethacin, the treatment would be surgical ligation.

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Finland
      • Helsinki, Finland
        • Helsinki Univeristy Central Hospital
      • Oulu, Finland, 90014
        • Department of Pediatrics, Oulu University Hospital
      • Tampere, Finland
        • Tampere University Hospital
      • Turku, Finland
        • Turku University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 4 months (Child)

Accepts Healthy Volunteers

No

Description

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.)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / 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 Names:
  • Paracetamol Fresenius Kabi 10mg/mL infusion solution
Drug: Ibuprofen
Standard therapy
Other Names:
  • 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: Ibuprofen
Standard therapy
Other Names:
  • Pedea 5mg/mL injection solution
Drug: 0.45% Sodium Chloride
Placebo comparator
Other Names:
  • NATRIUMKLORID BRAUN 4,5 mg/mL infusion solution
Experimental: Indomethacin 25mg/mL and Paracetamol10mg/mL
Intravenous (IV) indometahcin 25mg/mL q 24h for 3 days, dosages: 0.2mg/kg + 0.1mg/kg + 0.1mg/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 Names:
  • Paracetamol Fresenius Kabi 10mg/mL infusion solution
Drug: Indomethacin
Standard therapy
Other Names:
  • Liometacen 50mg/2mL injection
Placebo Comparator: Indomethacin 25mg/mL and 0.45 sodium chloride
Intravenous (IV) indomethacin 25mg/mL q 24h for 3 days, dosages: 0.2mg/kg + 0.1mg/kg + 0.1mg/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 Names:
  • NATRIUMKLORID BRAUN 4,5 mg/mL infusion solution
Drug: Indomethacin
Standard therapy
Other Names:
  • Liometacen 50mg/2mL injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Neonatal internsive care unit (NICU) stay up to 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Need for ductal therapies
Time Frame: NICU stay up to 12 weeks
Given ductal therapies after the study drug
NICU stay up to 12 weeks
Cardiac ultrasound findings
Time Frame: NICU stay up to 12 weeks
Ductal caliber (mm, mm/kg), LA/Ao ratio
NICU stay up to 12 weeks
Duration of any ventilation assist
Time Frame: NICU stay up to 12 weeks
The ventilation assist time pediod
NICU stay up to 12 weeks
Paracetamol serum levels
Time Frame: Study drug period up to 4 days
Measured paracetamol concentrations (mg/mL)
Study drug period up to 4 days
Paracetamol side effects
Time Frame: Study drug period plus 7 days, up to 10 days
Observed adverse events linked to study drug
Study drug period plus 7 days, up to 10 days
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
Hospital stay up to 18 weeks
Other long-term morbidity, and mortality
Time Frame: Hospital stay up to 18 weeks
Other severe diseases
Hospital stay up to 18 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Oulu

Collaborators

Turku University Hospital
Helsinki University Central Hospital
Tampere University Hospital

Investigators

  • Principal Investigator: Outi Aikio, MD, PhD, Oulu Univerisity Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 3, 2018

Primary Completion (Actual)

October 4, 2024

Study Completion (Actual)

October 4, 2024

Study Registration Dates

First Submitted

August 23, 2018

First Submitted That Met QC Criteria

August 23, 2018

First Posted (Actual)

August 27, 2018

Study Record Updates

Last Update Posted (Actual)

October 18, 2024

Last Update Submitted That Met QC Criteria

October 16, 2024

Last Verified

October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 38/2018

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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