The Preterm Infants' Paracetamol Study

NCT01938261 | Completed Phase 2 DMC

• 2 other identifiers: 100-20132013-001842-33
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Present randomized, controlled, double-blind trial investigates the efficacy and safety of early (\<24 h) intravenous paracetamol therapy for pain medication in very small premature infants. This phase 2 drug study focuses on the efficacy and safety of short-term use. The pharmacokinetics and pharmacodynamics of paracetamol, as well as the long-term effects, are studied. This study recruits preterm infants born less than 32 weeks gestational age and treated at the neonatal intensive care unit of Oulu University Hospital. The informed consent is asked from all parents. The first drug dose is given before 24 hours of age. Masked study drug is paracetamol infusion solution 10 mg/mL or placebo, 0.45% saline solution. The loading dose is 20 mg/kg, and the maintenance dose 7.5 mg/kg every 6 hours for 4 days. The exact date of the closure of ductus is studied by repeated echocardiographic examinations. The symptoms of pain are screened by a pain scale of preterm infants (NIAPAS). Patients are monitored for signs of possible side effects. After discharge from hospital, patients are examined at follow-up clinic for the first year every 3 months and at 2 years of age.

Conditions

Persistent Ductus Arteriosus; Complication of Prematurity; Pain or Discomfort in Intensive Care of Preterm Infants

Outcome Measures

Primary Outcomes (2)

• Ductus diameter mm/kg

  Measured by cardiac ultrasound

  at postnatal age of 5 days

• Cumulative dosage of morphine

  The amount of morphine doses administerd during the study

  at postnatal age of 5 days

Secondary Outcomes (6)

• Number of patients who received any treatment for persistent ductus arteriosus

  participants will be followed for the duration of NICU stay, an expected average of 12 weeks

• Postnatal age of ductus closure

  participants will be followed for the duration of NICU stay, an expected average of 12 weeks

• Left atrium to aorta ratio

  participants will be followed for the duration of NICU stay, an expected average of 12 weeks

• Number of apneic periods/day

  up to 5 days postnatal age

• NIAPAS screening scores

  up to 5 days postnatal age

Other Outcomes (4)

• Long-term morbidity diagnoses

  participants will be followed until 40 weeks gestational age, an expected average of 16 weeks

• Mortality

  participants will be followed until 40 weeks gestational age, an expected average of 16 weeks

• Paracetamol side effects

  participants will be followed until 40 weeks gestational age, an expected average of 16 weeks

Study Arms (2)

Paracetamol effect on ductus

EXPERIMENTAL

The first drug dose is given before 24 hours of age. Masked study drug is paracetamol infusion solution 10 mg/mL (PERFALGAN ®) or placebo, 0.45% saline solution. The loading dose is 20 mg/kg and the maintenance dose 7.5 mg kg every 6 hours for 4 days.

Drug: paracetamol; Drug: 0.45 % saline solution

Paracetamol effect on pain

EXPERIMENTAL

The first drug dose is given before 24 hours of age. Masked study drug is paracetamol infusion solution 10 mg/mL (PERFALGAN ®) or placebo, 0.45% saline solution. The loading dose is 20 mg/kg and the maintenance dose 7.5 mg kg every 6 hours for 4 days.

Drug: paracetamol; Drug: 0.45 % saline solution

Interventions

paracetamol DRUG

Also known as: Perfalgan 10 mg/ml infusion solution, Paracetamol Fresenius Kabi 10mg/ml

Paracetamol effect on ductus; Paracetamol effect on pain

0.45 % saline solution DRUG

Placebo

Also known as: Natriumklorid Braun 4.5mg/ml solution

Paracetamol effect on ductus; Paracetamol effect on pain

Eligibility Criteria

• Age: Up to 24 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• preterm infants born \< 32 weeks gestational age

You may not qualify if:

• congenital malformation
• lethal disease
• chromosomal abnormality
• persistent pulmonary hypertension of a newborn

Sponsors & Collaborators

• University of Oulu: lead

Study Sites (1)

Department of Pediatrics, Oulu University Hospital

Oulu, Finland

Location

Related Publications (2)

• Jasani B, Mitra S, Shah PS. Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low birth weight infants. Cochrane Database Syst Rev. 2022 Dec 15;12(12):CD010061. doi: 10.1002/14651858.CD010061.pub5.

  PMID: 36519620 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Ductus Arteriosus, Patent; Pain

Interventions

Acetaminophen; Saline Solution; Solutions

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Crystalloid Solutions; Isotonic Solutions; Pharmaceutical Preparations

Study Officials

• Timo Saarela, M.D., Ph. D.

  Oulu University Hospital

  PRINCIPAL INVESTIGATOR

• Mikko Hallman, M.D., Ph.D.

  University of Oulu

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Specialist in Pediatrics and Neonatology, M.D., Ph.D.

Study Record Dates

• First Submitted: August 22, 2013
• First Posted: September 10, 2013
• Study Start: August 1, 2013
• Primary Completion: July 15, 2024
• Study Completion: August 8, 2024
• Last Updated: October 18, 2024

Record last verified: 2024-10

Locations

FI (1)