Clinical trial NCT03641209: Extremely Low Gestatonal Age Infants' Paracetamol Study
Official title: Extremely Low Gestational Age Infants' Paracetamol Study: a Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Prematurity; Extreme
Low Birthweight, Extremely (999 Grams or Less)
Keywords: acetaminophen
ductus arteriosus
NIRS
intravenous
Lead sponsor: University of Oulu
Sponsor class: OTHER
First posted: 2018-08-21
Enrollment: 40
Sex: ALL
Maximum age (years): 96
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, controlled, one center trial
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.)

Primary outcomes:
measure: Ductal closure
timeFrame: Neonatal intensive care unit (NICU) treatment period up to 13 weeks
Secondary outcomes:
measure: Near-infrared spectroscopy values
timeFrame: Study drug period up to 10 days
measure: Paracetamol serum levels
timeFrame: Study drug period up to 10 days
measure: Paracetamol side effects
timeFrame: Neonatal intensive care unit (NICU) treatment period up to 13 weeks
measure: PDA
timeFrame: Neonatal intensive care unit (NICU) treatment period up to 13 weeks
measure: PDA, treated
timeFrame: Neonatal intensive care unit (NICU) treatment period up to 13 weeks
measure: Ventilatory assist
timeFrame: Neonatal intensive care unit (NICU) treatment period up to 13 weeks
measure: Complications of prematurity
timeFrame: The first hospitalization period up to 19 weeks
measure: Long term morbidity
timeFrame: The first hospitalization period up to 19 weeks
measure: Mortality
timeFrame: The first hospitalization period up to 19 weeks
Other outcomes:
Locations:
city: Oulu
country: Finland
facility: Department of Pediatrics, Oulu University Hospital
Study officials:
affiliation: Oulu University Hospital
name: Outi Aikio, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.