Not Yet RecruitingPhase 4ACTRN12615000981527

Oral paracetamol versus intravenous indomethacin for the treatment of patent ductus arteriosus in premature infants: A Randomised Control Trial (The OVID Trial)

In preterm infants with a haemodynamically significant ductus arteriosus, does oral paracetamol treatment compared to intravenous indomethacin result in greater narrowing or closure of the ductus arteriosus?

Sponsor

Monash Newborn, Monash Children's Hospital

Enrollment

150 participants

Start Date

Nov 2, 2015

Study Type

Interventional

Conditions

Prematurity

Summary

This will be a placebo randomised control trial conducted in the neonatal intensive care unit. The trial will compare oral paracetamol against current standard therapy for a haemodynamically significant ductus arteriosus, which is intravenous indomethacin.

Eligibility

Sex: Both males and femalesMin Age: 7 DayssMax Age: 14 Dayss

Inclusion Criteria9

Gestation: less than 32 weeks (up to 31 weeks 6 days) gestation
Post-natal (or post-gestation) age of greater than/equal to 7 days OR following the second routine cranial ultrasound assessment
Clinical suspicion of a haemodynamically significant PDA, e.g.
Active praecordium, loud murmur or wide pulse pressure
The need for respiratory support (defined as CPAP/NIMV/IMV/HFO) with FiO2 greater than or equal to 30%. These infants should have an echocardiographic assessment to confirm the presence of PDA
Echocardiographic evidence of either:
Significant left-to-right shunting across PDA (hsDA score of equal or greater than 6) comprising transductal diameter, velocity and left atrial aortic root ratio OR
A composite score of greater than or equal to than 16 based on the Sehgal score
Infant is on minimal enteral feed defined as less than or equal to 10ml/kg/day

Exclusion Criteria11

Major congenital abnormalities, including congenital heart disease
Severe intraventricular haemorrhage (IVH) (grade 3 or 4)
Evidence of coagulation dysfunction: Platelet count < 100,000/microlitre or presence of blood in endotracheal/gastric aspirate, haematuria
Intrauterine growth restriction defined as <3rd centile and/or reverse end diastolic flow on antenatal Dopplers.
Echocardiographic evidence of significant right-to-left shunting across PDA
Elevated serum creatinine > 100 micromol/L
Concerns about abdominal problems (feeding intolerance aspirates > feeding volume, bilious colour, abdominal distension)
Life threatening sepsis
Urine output of less than 1ml/kg/hour during the preceding 8 hours
Evidence of liver dysfunction or hyperbilirubinaemia requiring exchange transfusion
Decision not-to-treat by the attending neonatologist

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Interventions

Paracetamol, delivered orally Dosage: 15 mg/kg 6 hourly for 3 days, per course of treatment. The assessment for ductal status after the first course will be made by the neonatologist responsible for

Paracetamol, delivered orally Dosage: 15 mg/kg 6 hourly for 3 days, per course of treatment. The assessment for ductal status after the first course will be made by the neonatologist responsible for the infant who will base decision-making based on the echocardiography performed after the first course of treatment (within 72 hours after first treatment). The neonatologist will then decide if a second course of treatment is required (with input from paediatric cardiology). The second course of treatment will be given if on the second echocardiography (within 72 hours after first treatment) shows the presence of a hemodynamically significant ductus arteriosus and if the attending neonatologist decides. The maximum number of treatment courses will be two. Infant randomised to oral paracetamol arm will receive intravenous placebo. The intravenous placebo will be normal saline, which will be administered at 24 hourly interval for 3 days.