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Extremely Low Gestatonal Age Infants' Paracetamol Study

Phase 1
Completed
Conditions
Prematurity; Extreme
Low Birthweight, Extremely (999 Grams or Less)
Interventions
Registration Number
NCT03641209
Lead Sponsor
Outi Aikio
Brief Summary

In the present trial, early, intravenous paracetamol is compared to placebo in extremely premature or low birth weight infants in order to evaluate the effect on ductal closure.

Detailed Description

The purpose of this randomized, placebo-controlled, double-blind, phase 2, one center clinical trial is to study the efficacy and safety of early (\< 96 h) intravenous paracetamol in prophylactic closure of ductus arteriosus in extremely premature (gestational age \<28+0 wk, ELGA) or low birth weight (\<1000 g, ELBW) infants. The infants born extremely preterm or low birth weight are a focus of the study, since a small phase 2 study on paracetamol failed to demonstrate contraction of ductus arteriosus.

In the investigator's previous cohort of ELGA/ELBW infants, the numbers of patients who needed any therapies for patent ductus arteriosus (PDA) were 29 (23%) in the paracetamol exposed group, and 90 (54%) in the control group. As demonstrated in a phase 2 study, the early paracetamol treatment induced the closure of ductus arteriosus: the mean (SD) ductal closure age was 177 (338) h in the whole paracetamol group. However, in the subgroup of ELGA infants born before 28 gestation weeks (n=14), the mean (SD) ductal closure ages in the paracetamol and placebo groups were 491 (504) h and 858 (719) h, respectively.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
40
Inclusion Criteria
  • Premature infants born before 28+0 gestation weeks and/or birth weight less than 1000g
Exclusion Criteria
  • Severe malformation or suspected chromosomal defect or other very severe life-threatening disease (e.g. very severe birth asphyxia or persistent pulmonary hypertension, etc.)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo0.45% sodium chloride (NaCl) solution, equal amounts in mL as would have been given the experimental drug
ParacetamolParacetamol 10mg/mL infusion solutionParacetamol 10 mg/mL infusion solution, intravenous loading dose 20 mg/kg, followed by maintenance dose 7.5 mg/kg every 6 h up to 9 days
Primary Outcome Measures
NameTimeMethod
Ductal closureNeonatal intensive care unit (NICU) treatment period up to 13 weeks

Postnatal age of the observed closure of ductus arteriosus

Secondary Outcome Measures
NameTimeMethod
MortalityThe first hospitalization period up to 19 weeks

Mortality

Complications of prematurityThe first hospitalization period up to 19 weeks

The long term complications of prematurity (moderate-to-severe bronchopulmonary dysplasia (BPD), intraventricular hemorrhage gr 2-4, moderate to severe necrotizing enterocolitis, retinopathy of prematurity (ROP) needing therapy)

Paracetamol serum levelsStudy drug period up to 10 days

Paracetamol serum levels

Paracetamol side effectsNeonatal intensive care unit (NICU) treatment period up to 13 weeks

Any observed or detected paracetamol side effects

Long term morbidityThe first hospitalization period up to 19 weeks

Other long-term morbidity

PDA, treatedNeonatal intensive care unit (NICU) treatment period up to 13 weeks

The need for PDA therapies (ibuprofen, paracetamol, ligation)

Near-infrared spectroscopy valuesStudy drug period up to 10 days

Near-infrared spectroscopy values

PDANeonatal intensive care unit (NICU) treatment period up to 13 weeks

Open ductus arteriosus without any traditional PDA therapies

Ventilatory assistNeonatal intensive care unit (NICU) treatment period up to 13 weeks

The duration of any ventilation assist, days

Trial Locations

Locations (1)

Department of Pediatrics, Oulu University Hospital

🇫🇮

Oulu, Finland

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