Paracetamol And Ibuprofen/Indomethacin in Closing Patent Ductus Arteriosus
- Conditions
- Patent Ductus Arteriosus
- Interventions
- Registration Number
- NCT03648437
- Lead Sponsor
- University of Oulu
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 22
- 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.
- severe malformation or suspected chromosomal defect
- other very severe life-threatening disease (e.g. very severe birth asphyxia or persistent pulmonary hypertension, etc.)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Indomethacin 25mg/mL and Paracetamol10mg/mL Paracetamol 10Mg/mL Intravenous (IV) indometahcin 25mg/mL q 24h for 3 days, dosages: 0.2mg/kg + 0.1mg/kg + 0.1mg/kg and IV paracetamol 10mg/mL for 3 days: loading dose 20mg/kg, following 7.5mg/kg q 6h (up to12 doses) Indomethacin 25mg/mL and 0.45 sodium chloride 0.45% Sodium Chloride Intravenous (IV) indomethacin 25mg/mL q 24h for 3 days, dosages: 0.2mg/kg + 0.1mg/kg + 0.1mg/kg and NaCl 0.45% for 3 days, the same amount in mL as would have been given IV paracetamol Pedea 5mg/mL and Paracetamol 10mg/mL Paracetamol 10Mg/mL Intravenous (IV) ibuprofen 5mg/mL q 24h for 3 days, dosages: 10mg/kg + 5mg/kg + 5mg/kg and IV paracetamol 10mg/mL for 3 days: loading dose 20mg/kg, following 7.5mg/kg q 6h (up to12 doses) Pedea 5mg/mL and 0.45 sodium chloride 0.45% Sodium Chloride IV ibuprofen 5mg/mL q 24h for 3 days, dosages: 10mg/kg + 5mg/kg + 5mg/kg and NaCl 0.45% for 3 days, the same amount in mL as would have been given IV paracetamol Pedea 5mg/mL and Paracetamol 10mg/mL Ibuprofen Intravenous (IV) ibuprofen 5mg/mL q 24h for 3 days, dosages: 10mg/kg + 5mg/kg + 5mg/kg and IV paracetamol 10mg/mL for 3 days: loading dose 20mg/kg, following 7.5mg/kg q 6h (up to12 doses) Pedea 5mg/mL and 0.45 sodium chloride Ibuprofen IV ibuprofen 5mg/mL q 24h for 3 days, dosages: 10mg/kg + 5mg/kg + 5mg/kg and NaCl 0.45% for 3 days, the same amount in mL as would have been given IV paracetamol Indomethacin 25mg/mL and Paracetamol10mg/mL Indomethacin Intravenous (IV) indometahcin 25mg/mL q 24h for 3 days, dosages: 0.2mg/kg + 0.1mg/kg + 0.1mg/kg and IV paracetamol 10mg/mL for 3 days: loading dose 20mg/kg, following 7.5mg/kg q 6h (up to12 doses) Indomethacin 25mg/mL and 0.45 sodium chloride Indomethacin Intravenous (IV) indomethacin 25mg/mL q 24h for 3 days, dosages: 0.2mg/kg + 0.1mg/kg + 0.1mg/kg and NaCl 0.45% for 3 days, the same amount in mL as would have been given IV paracetamol
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Cardiac ultrasound findings NICU stay up to 12 weeks Ductal caliber (mm, mm/kg), LA/Ao ratio
Paracetamol side effects Study drug period plus 7 days, up to 10 days Observed adverse events linked to study drug
Other long-term morbidity, and mortality Hospital stay up to 18 weeks Other severe diseases
Paracetamol serum levels Study drug period up to 4 days Measured paracetamol concentrations (mg/mL)
Need for ductal therapies NICU stay up to 12 weeks Given ductal therapies after the study drug
Duration of any ventilation assist NICU stay up to 12 weeks The ventilation assist time pediod
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
Trial Locations
- Locations (4)
Helsinki Univeristy Central Hospital
🇫🇮Helsinki, Finland
Department of Pediatrics, Oulu University Hospital
🇫🇮Oulu, Finland
Tampere University Hospital
🇫🇮Tampere, Finland
Turku University Hospital
🇫🇮Turku, Finland