Extremely Low Gestatonal Age Infants' Paracetamol Study

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Prematurity; Extreme, Low Birthweight, Extremely (999 Grams or Less)

Intervention / Treatment
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* Drug: Paracetamol 10mg/mL infusion solution
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.)

Ages Eligible for Study
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Maximum Age: 96 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, controlled, one center trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paracetamol<br>Paracetamol 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 | Drug: Paracetamol 10mg/mL infusion solution<br>* Intravenous paracetamol solution for infusion<br>* Other names: Paracetamol Fresenius Kabi 10 mg/mL infusion solution;|
| Placebo Comparator: Placebo<br>0.45% sodium chloride (NaCl) solution, equal amounts in mL as would have been given the experimental drug | Other: Placebo<br>* Half physiological saline solution as the non-active placebo solution<br>* Other names: Natriumklorid Braun 4,5mg/mL solution for infusion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ductal closure | Postnatal age of the observed closure of ductus arteriosus | Neonatal intensive care unit (NICU) treatment period up to 13 weeks | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ductus arteriosus, acetaminophen, NIRS, intravenous