Patent Ductus Arteriosus
Conditions
Keywords
acetaminophen, ibuprofen, preterm infant, near infra-red spectroscopy, indomethacin
Brief summary
The purpose of this pilot trial is to study efficacy and safety of simultaneous intravenous (iv) ibuprofen/indomethacin and paracetamol medications in the closure of patent ductus arteriosus (PDA) in preterm infants. It is randomized, placebo-controlled, double-blind, phase 1, multicenter, clinical trial.
Detailed description
Premature infants (born before 37 weeks gestational age) with patent ductus arteriosus (PDA) are the focus of the study since no trials on the additive efficacy of these two medications on the contraction of ductus arteriosus are available. Preterm infants who are diagnosed to have a hemodynamically significant PDA and who, according to the decision of the attending clinician, need ibuprofen/indomethacin therapy, are eligible to this trial. If the parents deny the consent, the patient will be treated according to the standard PDA treatment: three days' iv ibuprofen Pedea® 5mg/ml solution infusion (Oulu, Helsinki, Tartu) dosing: 10mg/kg + 5mg/kg + 5mg/kg (q24h); or three days' iv indomethacin (Turku) 0.2mg/kg + 0.1mg/kg + 0.1mg/kg (q24h). In case of any contraindications for ibuprofen/indomethacin, the treatment would be surgical ligation.
Interventions
DRUGParacetamol 10Mg/mL
Experimental drug
DRUG0.45% Sodium Chloride
Placebo comparator
DRUGIbuprofen
Standard therapy
DRUGIndomethacin
Standard therapy
Sponsors
Helsinki University Central Hospital
Turku University Hospital
Tampere University Hospital
University of Oulu
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
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 neonatal intensive care unit, 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
multicenter, randomized, placebo-controlled, double-blind, clinical trial
Eligibility
Sex/Gender
ALL
Age
No minimum to 4 Months
Healthy volunteers
No
Inclusion criteria
* Preterm infants (born before 37+0 gestation weeks) who are diagnosed to have a hemodynamically significant PDA and who, according to the decision of the attending clinician, need ibuprofen therapy, are eligible to this trial.
Exclusion criteria
* severe malformation or suspected chromosomal defect * 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 internsive care unit (NICU) stay up to 12 weeks | Number of patients with ductal contraction without need for other PDA therapies |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Need for ductal therapies | NICU stay up to 12 weeks | Given ductal therapies after the study drug |
| Cardiac ultrasound findings | NICU stay up to 12 weeks | Ductal caliber (mm, mm/kg), LA/Ao ratio |
| Duration of any ventilation assist | NICU stay up to 12 weeks | The ventilation assist time pediod |
| Paracetamol serum levels | Study drug period up to 4 days | Measured paracetamol concentrations (mg/mL) |
| Long term complications of prematurity | Hospital stay up to 18 weeks | Moderate-to-severe bronchopulmonary dysplasia, intraventricular hemorrhage grade 2-4, moderate to severe necrotizing enterocolitis, retinopathy of prematurity needing therapy |
| Other long-term morbidity, and mortality | Hospital stay up to 18 weeks | Other severe diseases |
| Paracetamol side effects | Study drug period plus 7 days, up to 10 days | Observed adverse events linked to study drug |
Countries
Finland
Outcome results
None listed