Extremely Low Gestatonal Age Infants' Paracetamol Study

Prematurity; Extreme Clinical Trial

— Paras  

Official title:

Extremely Low Gestational Age Infants' Paracetamol Study: a Randomized Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03641209
• Other study ID #: 39/2018
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 3, 2018
• Est. completion date: March 1, 2024

Study information

• Verified date: March 2024
• Source: University of Oulu
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: March 1, 2024
• Est. primary completion date: November 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 96 Hours

Eligibility

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.)

Related Conditions & MeSH terms

• Birth Weight
• Low Birthweight, Extremely (999 Grams or Less)
• Prematurity; Extreme

Intervention

Drug:
• Paracetamol 10mg/mL infusion solution
Intravenous paracetamol solution for infusion

Other:
• Placebo
Half physiological saline solution as the non-active placebo solution

Locations

Country	Name	City	State
Finland	Department of Pediatrics, Oulu University Hospital	Oulu

Sponsors (1)

Lead Sponsor	Collaborator
Outi Aikio

Country where clinical trial is conducted

Finland, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ductal closure	Postnatal age of the observed closure of ductus arteriosus	Neonatal intensive care unit (NICU) treatment period up to 13 weeks
Secondary	Near-infrared spectroscopy values	Near-infrared spectroscopy values	Study drug period up to 10 days
Secondary	Paracetamol serum levels	Paracetamol serum levels	Study drug period up to 10 days
Secondary	Paracetamol side effects	Any observed or detected paracetamol side effects	Neonatal intensive care unit (NICU) treatment period up to 13 weeks
Secondary	PDA	Open ductus arteriosus without any traditional PDA therapies	Neonatal intensive care unit (NICU) treatment period up to 13 weeks
Secondary	PDA, treated	The need for PDA therapies (ibuprofen, paracetamol, ligation)	Neonatal intensive care unit (NICU) treatment period up to 13 weeks
Secondary	Ventilatory assist	The duration of any ventilation assist, days	Neonatal intensive care unit (NICU) treatment period up to 13 weeks
Secondary	Complications of prematurity	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)	The first hospitalization period up to 19 weeks
Secondary	Long term morbidity	Other long-term morbidity	The first hospitalization period up to 19 weeks
Secondary	Mortality	Mortality	The first hospitalization period up to 19 weeks