Paracetamol and Patent Ductus Arteriosus (PDA)

Study Overview
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Brief Summary
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The investigators propose that paracetamol will be similarly effective to ibuprofen in treating PDA in the premature neonate, with fewer side effects.

Detailed Description
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Preterm neonates with a hemodynamically significant PDA will potentially be candidates for study. After obtaining parental consent, the infants will be prospectively and randomly assigned to one of two groups: 1.po Paracetamol at a dose of 15 mg/kg every 6 hours at x 3 days or Group 2- IV indomethacin - 0.2 mg/kg/dose q 12h for three doses; or IV Ibuprofen 10 mg/kg infused over 15 minutes, followed by two doses of 5mg/kg each at 24 hour intervals (total of 3 doses).Clinical staff will be blinded as to the study group assignment of the babies and since the group 1 drug is to be given every six hours, all babies will receive a parenteral substance every 6 hours. For Group 2 infants, the intermittent doses will be IV D5W alternating with drug.All infants will fed trophic feeds (20 cc/kg/day) during the treatment for ductal closure.

Official Title
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Paracetamol in the Treatment of Patent Ductus Arteriosus in the Premature Neonate

Conditions
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Patent Ductus Arteriosus

Intervention / Treatment
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* Drug: Paracetamol
* Drug: NSAID
* Drug: D5W


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Echocardiographic diagnosis of hemodynamically significant patent ductus arteriosus Exclusion Criteria: Major congenital anomalies Life-threatening infection Active NEC and/or intestinal perforation Recent (within the previous 24 hours) intraventricular hemorrhage Grade 3-4 Urine output <1 ml per kilogram per hour during the preceding 8 hours Serum creatinine concentration of >1.6 mg % Platelet count of <60,000 per cc.

Ages Eligible for Study
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Minimum Age: 2 Days
Maximum Age: 2 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paracetamol<br>Babies with hsPDA will be treated with paracetamol 15 mg/kg/dose x 4/day for three days | Drug: Paracetamol<br>* po Paracetamol 15 mg/kg every 6 hours x 3 days<br>|
| Experimental: NSAID<br>Babies with hsPDA will be randomized to treatment with IV indomethacin 17 mcg/kg/hr x 36 hr | Drug: NSAID<br>* IV indomethacin 2 mg/kg/dose for three doses at 12 hour intervals; or IV Ibuprofen 10 mg/kg infused over 15 minutes, followed by two doses of 5mg/kg each at 24 hour intervals (total of 3 doses).<br>Drug: D5W<br>* Since the paracetamol is given q 6 hours, in order to maintain blinding of the clinical staff, a placebo (D5W) must be given intermittently between the doses of NSAID such that each infant will receive drug every 6 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Closure of the Ductus |  | 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absence of peripheral vasoconstriction | Doppler flow velocity in anterior cerebral artery, superior mesenteric artery and renal artery will be measured before and after pharmacologic treatment. | 48 hours | 
| Absence of hepatotoxicity | Liver function will be compared between the two study groups at 1 week following completion of pharmacologic treatment | 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PDA, Paracetamol, Indomethacin, Ibuprofen