None listed
Conditions
Brief summary
Background: In term infants functional closure of the PDA usually occurs in the first 72 hours, but may take longer in preterm infants. The primary rationale for treatment of the duct is that the left to right shunt across the PDA can cause deleterious systemic and pulmonary haemodynamic effects. This potentially leads to excessive pulmonary blood flow that may result in pulmonary haemorrhage or a need for increased respiratory support (oxygen and/or positive pressure) and systemic circulatory compromise causing abnormal organ function and tissue injury. The need to treat a PDA at a later stage when acute complications are less likely is currently controversial. Though the data on the outcome of preterm infants with persistent ductus arteriosus have been scarce, there has been a study addressing this issue which reports eightfold increase in mortality of VLBW neonates with persistent PDA. A recent abstract publication described a case series of 5 infants who appeared to have spontaneous late PDA closure following the use of paracetamol for unrelated indications. Paracetamol is a commonly used medication in infants with a relatively benign side effect profile, so if found to be efficacious, could provide a useful alternative for treatment of PDA. Aim: 1.To study the effect of paracetamol given orally in closure of late PDA in premature neonates; 2. Examine the safety and efficacy profile of paracetamol. Study design: a prospective randomised, blinded, placebo controlled trial. Population: Preterm infants born <33 weeks gestational age with a persistent PDA who are >4 weeks of postnatal age and tolerating at least 50% enteral feeds. Method: A clinician performed ultrasound (CPU) by qualified neonatal medical staff will assess ductal size and haemodynamic significance at 4 weeks of age. Any abnormal liver function will be excluded prior to commencement of study medication using routine blood tests. After randomisation, the study group will receive paracetamol as per Australian guidelines for neonates(25mg/kg loading dose, followed by maintenance dose of 15mg/kg at an interval appropriate for gestational age. The placebo group will receive the same volume of oral placebo solution, most likely sucrose. The study medication course will be for 5 days. A CPU by a clinician blinded to study medication allocation will be performed after 48 hours of medication administration and again after 5 days to document ductal patency and haemodynamic significance. 0.5ml of blood will be collected in a lithium heparin tube for repeat liver function tests and paracetamol serum levels 48 hours after commencement of study medication and again at completion of study medication on day 5. Some of these tests may overlap with required routine blood tests and therefore may not be extra. The primary outcome will be succesful closure of PDA as documented on clinician performed ultrasound.
Interventions
A clinician performed ultrasound (CPU) by qualified neonatal medical staff will assess ductal size and haemodynamic significance. This will be documented utilising the standard measures of flow pattern, diastolic flow in the descending aorta, left atrium / aortic ratio (LA/AO), left pulmonary artery diastolic velocity (LPAD), left ventricular end diastolic diameter (LVEDD) and left ventricular output (LVO).
If not routinely collected in the previous week, a blood sample of 0.5ml will then be col
A clinician performed ultrasound (CPU) by qualified neonatal medical staff will assess ductal size and haemodynamic significance. This will be documented utilising the standard measures of flow pattern, diastolic flow in the descending aorta, left atrium / aortic ratio (LA/AO), left pulmonary artery diastolic velocity (LPAD), left ventricular end diastolic diameter (LVEDD) and left ventricular output (LVO). If not routinely collected in the previous week, a blood sample of 0.5ml will then be collected for elevated Liver Function Tests (LFTs): alanine transaminase and aspartate transaminase, plus conjugated SBR levels, to detect any abnormal liver function prior to commencement of study medication. After randomisation, the study group will receive paracetamol as per Neofax guidelines with an oral loading dose of 25mg/kg/dose, followed by a maintenance dose of 15mg/kg/dose. The maintenance dosing interval will be 8 hourly in preterm infants more than or equal to 32 weeks postmenstrual age, 12 hourly in preterm less than 32 weeks postmenstrual age, and 6 hourly in term infants. The total duration of treatment will be 5 days in all groups.
Sponsors
A/Professor Martin Kluckow
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
4 Weeks to 20 Weeks
Healthy volunteers
No
Inclusion criteria
1. Babies with a persistent PDA born <33 weeks gestational age who are >4 weeks of postnatal age and tolerating at least 50% (i.e. 80ml/kg/day) of enteral feeds 2. Echocardiographic findings of a PDA with a Colour Doppler duct size more than 1.5mm with pulsatile pattern with or without oxygen and/or CPAP support. 3. Informed written parental consent
Exclusion criteria
1. PDA with evidence of congestive cardiac failure, signs include tachycardia; venous congestion; high catecholamine levels; and, ultimately, insufficient cardiac output with poor perfusion and end-organ compromise. 2. Abnormal liver function tests : a. Elevated alanine transaminase (twice normal level for corrected gestation) b. Elevated aspartate transaminase (twice normal level for corrected gestation) c. Elevated conjugated bilirubin (>80mmol/L)
Outcome results
None listed