Paracetamol And Ibuprofen/Indomethacin in Closing Patent Ductus Arteriosus of Preterm Infants - Randomised, Placebo-controlled Multicentre Trial
Overview
- Phase
- Phase 1
- Intervention
- Paracetamol 10Mg/mL
- Conditions
- Patent Ductus Arteriosus
- Sponsor
- University of Oulu
- Enrollment
- 22
- Locations
- 4
- Primary Endpoint
- Ductal closure
- Status
- Terminated
- Last Updated
- last year
Overview
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.
Investigators
Outi Aikio
MD, PhD, Docent, Specialist in Peditrics and Neonatology
University of Oulu
Eligibility Criteria
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.)
Arms & Interventions
Pedea 5mg/mL and 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)
Intervention: Paracetamol 10Mg/mL
Pedea 5mg/mL and 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)
Intervention: Ibuprofen
Pedea 5mg/mL and 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
Intervention: 0.45% Sodium Chloride
Pedea 5mg/mL and 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
Intervention: Ibuprofen
Indomethacin 25mg/mL and Paracetamol10mg/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)
Intervention: Paracetamol 10Mg/mL
Indomethacin 25mg/mL and Paracetamol10mg/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)
Intervention: Indomethacin
Indomethacin 25mg/mL and 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
Intervention: 0.45% Sodium Chloride
Indomethacin 25mg/mL and 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
Intervention: Indomethacin
Outcomes
Primary Outcomes
Ductal closure
Time Frame: Neonatal internsive care unit (NICU) stay up to 12 weeks
Number of patients with ductal contraction without need for other PDA therapies
Secondary Outcomes
- Cardiac ultrasound findings(NICU stay up to 12 weeks)
- Paracetamol side effects(Study drug period plus 7 days, up to 10 days)
- Other long-term morbidity, and mortality(Hospital stay up to 18 weeks)
- Paracetamol serum levels(Study drug period up to 4 days)
- Need for ductal therapies(NICU stay up to 12 weeks)
- Duration of any ventilation assist(NICU stay up to 12 weeks)
- Long term complications of prematurity(Hospital stay up to 18 weeks)