Low Birthweight, Extremely (999 Grams or Less), Prematurity; Extreme
Conditions
Keywords
acetaminophen, ductus arteriosus, NIRS, intravenous
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.
Interventions
DRUGParacetamol 10mg/mL infusion solution
Intravenous paracetamol solution for infusion
OTHERPlacebo
Half physiological saline solution as the non-active placebo solution
Sponsors
Outi Aikio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Placebo, 0.45 % saline, is similar to paracetamol, both being clear liquids, so the staff will remain unaware which drug the patient receives. The study drug will be kept and prepared away from the NICU, at the separate ward 55 office, in a locked cabinet. The study drug will be prepared by the research nurse, the pharmacist of the ward, or during nighttime, by a nurse who does not participate in the study patients' treatment in any way.
Intervention model description
Randomized, controlled, one center trial
Eligibility
Sex/Gender
ALL
Age
No minimum to 96 Hours
Healthy volunteers
No
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.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ductal closure | Neonatal intensive care unit (NICU) treatment period up to 13 weeks | Postnatal age of the observed closure of ductus arteriosus |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Paracetamol serum levels | Study drug period up to 10 days | Paracetamol serum levels |
| Paracetamol side effects | Neonatal intensive care unit (NICU) treatment period up to 13 weeks | Any observed or detected paracetamol side effects |
| PDA | Neonatal intensive care unit (NICU) treatment period up to 13 weeks | Open ductus arteriosus without any traditional PDA therapies |
| PDA, treated | Neonatal intensive care unit (NICU) treatment period up to 13 weeks | The need for PDA therapies (ibuprofen, paracetamol, ligation) |
| Near-infrared spectroscopy values | Study drug period up to 10 days | Near-infrared spectroscopy values |
| Complications of prematurity | The 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) |
| Long term morbidity | The first hospitalization period up to 19 weeks | Other long-term morbidity |
| Mortality | The first hospitalization period up to 19 weeks | Mortality |
| Ventilatory assist | Neonatal intensive care unit (NICU) treatment period up to 13 weeks | The duration of any ventilation assist, days |
Countries
Finland
Outcome results
None listed