Paracetamol and Patent Ductus Arteriosus (PDA)

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

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

Study Overview

• Status: Unknown
• Conditions: Patent Ductus Arteriosus
• Intervention / Treatment: Drug: Paracetamol; Drug: NSAID; Drug: D5W

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Israel
  • Jerusalem, Israel, 91031
    • Recruiting
    • Shaare Zedek Medical Center
    • Principal Investigator: Cathy Hammerman, MD
    • Contact: Cathy Hammerman, MD; Phone Number: +9722666-6238; Email: cathy@cc.huji.ac.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 days to 2 weeks (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Paracetamol; Babies with hsPDA will be treated with paracetamol 15 mg/kg/dose x 4/day for three days	Drug: Paracetamol; po Paracetamol 15 mg/kg every 6 hours x 3 days
Experimental: NSAID; Babies with hsPDA will be randomized to treatment with IV indomethacin 17 mcg/kg/hr x 36 hr	Drug: NSAID; 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).; Drug: D5W; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Shaare Zedek Medical Center
• Investigators: Principal Investigator: Cathy Hammerman, MD, Hebrew University Faculty of Medicine

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: February 6, 2011
• First Submitted That Met QC Criteria: February 7, 2011
• First Posted (Estimate): February 8, 2011

Study Record Updates

• Last Update Posted (Estimate): December 19, 2012
• Last Update Submitted That Met QC Criteria: December 18, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: PDA; Ibuprofen; Paracetamol; Indomethacin
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Heart Defects, Congenital; Cardiovascular Abnormalities; Ductus Arteriosus, Patent; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: SZMC-Hammerman-Acamol-2011