The Preterm Infants' Paracetamol Study
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- University of Oulu
- Enrollment
- 120
- Locations
- 1
- Primary Endpoint
- Ductus diameter mm/kg
Study Overview
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.
Detailed Description
1 Hypotheses and aims: The aim of the present study is to evaluate the safety and efficacy of intravenous paracetamol in pain medication for small preterm infants in a randomized, controlled, double-blind trial. The primary outcome of the pain medication arm is the need for morphine medication (doses). The secondary outcomes are paracetamol serum concentrations, the side effects of paracetamol (possible hepatic dysfunction), neonatal and long-term morbidity, and mortality.
The primary outcome in the phase 2 ductus study-arm was diminishing of the ductal caliber at 5 days postnatal age. This study arm has been finalized and the results were published on 2016 (Härkin et al).
Hypotheses:
I. Hypothesis. Early, intravenous paracetamol is effective and safe therapy in the relief of pain and discomfort of a preterm infant.
II. Hypothesis. Paracetamol levels of a preterm infant remain in safety limits with study dosages.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- — to 24 Hours (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •preterm infants born < 32 weeks gestational age
Exclusion Criteria
- •congenital malformation
- •lethal disease
- •chromosomal abnormality
- •persistent pulmonary hypertension of a newborn
Arms & Interventions
Paracetamol effect on ductus
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.
Intervention: paracetamol (Drug)
Paracetamol effect on ductus
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.
Intervention: 0.45 % saline solution (Drug)
Paracetamol effect on pain
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.
Intervention: paracetamol (Drug)
Paracetamol effect on pain
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.
Intervention: 0.45 % saline solution (Drug)
Outcomes
Primary Outcomes
Ductus diameter mm/kg
Time Frame: at postnatal age of 5 days
Measured by cardiac ultrasound
Cumulative dosage of morphine
Time Frame: at postnatal age of 5 days
The amount of morphine doses administerd during the study
Secondary Outcomes
- Number of apneic periods/day(up to 5 days postnatal age)
- Duration of mechanical ventilation(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)
- 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)
- Left atrium to aorta ratio(participants will be followed for the duration of NICU stay, an expected average of 12 weeks)
- NIAPAS screening scores(up to 5 days postnatal age)
Investigators
Outi Aikio
Specialist in Pediatrics and Neonatology, M.D., Ph.D.
University of Oulu