Paracetamol And Ibuprofen/Indomethacin in Closing Patent Ductus Arteriosus

NCT03648437 | Terminated Phase 1 DMC

• 1 other identifier: 38/2018
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Patent Ductus Arteriosus

Keywords

acetaminophen; ibuprofen; preterm infant; near infra-red spectroscopy; indomethacin

Outcome Measures

Primary Outcomes (1)

• Ductal closure

  Number of patients with ductal contraction without need for other PDA therapies

  Neonatal internsive care unit (NICU) stay up to 12 weeks

Secondary Outcomes (7)

• Need for ductal therapies

  NICU stay up to 12 weeks

• Cardiac ultrasound findings

  NICU stay up to 12 weeks

• Duration of any ventilation assist

  NICU stay up to 12 weeks

• Paracetamol serum levels

  Study drug period up to 4 days

• Paracetamol side effects

  Study drug period plus 7 days, up to 10 days

Study Arms (4)

Pedea 5mg/mL and Paracetamol 10mg/mL

EXPERIMENTAL

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; Drug: Ibuprofen

Pedea 5mg/mL and 0.45 sodium chloride

PLACEBO COMPARATOR

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; Drug: Ibuprofen

Indomethacin 25mg/mL and Paracetamol10mg/mL

EXPERIMENTAL

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; Drug: Indomethacin

Indomethacin 25mg/mL and 0.45 sodium chloride

PLACEBO COMPARATOR

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; Drug: Indomethacin

Interventions

Paracetamol 10Mg/mL DRUG

Experimental drug

Also known as: Paracetamol Fresenius Kabi 10mg/mL infusion solution

Indomethacin 25mg/mL and Paracetamol10mg/mL; Pedea 5mg/mL and Paracetamol 10mg/mL

0.45% Sodium Chloride DRUG

Placebo comparator

Also known as: NATRIUMKLORID BRAUN 4,5 mg/mL infusion solution

Indomethacin 25mg/mL and 0.45 sodium chloride; Pedea 5mg/mL and 0.45 sodium chloride

Ibuprofen DRUG

Standard therapy

Also known as: Pedea 5mg/mL injection solution

Pedea 5mg/mL and 0.45 sodium chloride; Pedea 5mg/mL and Paracetamol 10mg/mL

Indomethacin DRUG

Standard therapy

Also known as: Liometacen 50mg/2mL injection

Indomethacin 25mg/mL and 0.45 sodium chloride; Indomethacin 25mg/mL and Paracetamol10mg/mL

Eligibility Criteria

• Age: Up to 4 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• University of Oulu: lead
• Helsinki University Central Hospital: collaborator
• Turku University Hospital: collaborator
• Tampere University Hospital: collaborator

Study Sites (4)

Helsinki Univeristy Central Hospital

Helsinki, Finland

Location

Department of Pediatrics, Oulu University Hospital

Oulu, 90014, Finland

Location

Tampere University Hospital

Tampere, Finland

Location

Turku University Hospital

Turku, Finland

Location

Related Publications (5)

• Harkin P, Harma A, Aikio O, Valkama M, Leskinen M, Saarela T, Hallman M. Paracetamol Accelerates Closure of the Ductus Arteriosus after Premature Birth: A Randomized Trial. J Pediatr. 2016 Oct;177:72-77.e2. doi: 10.1016/j.jpeds.2016.04.066. Epub 2016 May 20.

  PMID: 27215779 BACKGROUND

• Juujarvi S, Saarela T, Hallman M, Aikio O. Intravenous paracetamol was associated with closure of the ductus arteriosus in extremely premature infants. Acta Paediatr. 2018 Apr;107(4):605-610. doi: 10.1111/apa.14137. Epub 2017 Nov 17.

  PMID: 29105147 BACKGROUND

• Harma A, Aikio O, Hallman M, Saarela T. Intravenous Paracetamol Decreases Requirements of Morphine in Very Preterm Infants. J Pediatr. 2016 Jan;168:36-40. doi: 10.1016/j.jpeds.2015.08.003. Epub 2015 Aug 29.

  PMID: 26323200 BACKGROUND

• Aikio O, Harkin P, Saarela T, Hallman M. Early paracetamol treatment associated with lowered risk of persistent ductus arteriosus in very preterm infants. J Matern Fetal Neonatal Med. 2014 Aug;27(12):1252-6. doi: 10.3109/14767058.2013.854327. Epub 2013 Oct 31.

  PMID: 24111688 BACKGROUND

• Juujarvi S, Kallankari H, Patsi P, Leskinen M, Saarela T, Hallman M, Aikio O. Follow-up study of the early, randomised paracetamol trial to preterm infants, found no adverse reactions at the two-years corrected age. Acta Paediatr. 2019 Mar;108(3):452-458. doi: 10.1111/apa.14614. Epub 2018 Nov 12.

  PMID: 30325529 BACKGROUND

Related Links

• Thesis, Sanna Juujärvi, MB
• Thesis, Pia Härkin, MD

MeSH Terms

Conditions

Ductus Arteriosus, Patent; Premature Birth

Interventions

Acetaminophen; Sodium Chloride; Ibuprofen; Indomethacin; Injections

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Outi Aikio, MD, PhD

  Oulu Univerisity Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Docent, Specialist in Peditrics and Neonatology

Model Details: multicenter, randomized, placebo-controlled, double-blind, clinical trial

Study Record Dates

• First Submitted: August 23, 2018
• First Posted: August 27, 2018
• Study Start: September 3, 2018
• Primary Completion: October 4, 2024
• Study Completion: October 4, 2024
• Last Updated: October 18, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

FI (4)