An Escalating Dose Indomethacin for the Treatment of Persistent Patent Ductus Arteriosus (PDA) In Preterm Infants

Condition(s) targeted: Patent Ductus Arteriosus

Intervention: Indomethacin (Drug)

Phase: Phase 2/Phase 3

Status: Recruiting

Sponsored by: University of Calgary

Official(s) and/or principal investigator(s):
Amuchou S Soraisham, MD, DM, Principal Investigator, Affiliation: University of Calgary

Overall contact:
Amuchou S Soraisham, MD, DM, Phone: (403) 944-1615, Email: amuchou.soraisham@albertahealthservices.ca

A large patent ductus arteriosus (PDA) is associated with congestive heart failure, pulmonary hemorrhage, chronic lung disease (CLD), necrotizing enterocolitis (NEC) and intraventricular bleeding. Indomethacin is the first line of treatment for PDA. Failure of ductal closure with the first course of indomethacin is reported in 30-40% of infants, with a higher failure rate in infants weighing < 1000 gm. PDA ligation is associated with early postoperative hypotension, oxygenation failure and adverse neurodevelopmental outcome in preterm infants. The use of escalating doses of Indomethacin in the treatment of persistent PDA was found to be safe and decreased the need for PDA ligation without adverse effects in one observational study. We hypothesize that the use of an escalated dose of intravenous indomethacin will result in an increase in the probability of survival without need for surgical ligation of PDA as compared to a standard dose indomethacin in newborn infants < 29 weeks of gestational age with persistent PDA.

Official title: An Escalating Dose Indomethacin for the Treatment of Persistent Patent Ductus Arteriosus (PDA) In Preterm Infants- A Randomized Pilot Study

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Survival without PDA ligation at discharge

Secondary outcome:

PDA closure rate

Incidence of necrotizing enterocolitis, renal failure and bronchopulmonary dysplasia

Detailed description: This study is a randomized control trial. Those eligible infants will be randomized to either a Standard Dose group or to Escalating Dose indomethacin group after obtaining parental consent. The infants randomized to the standard dose group will receive indomethacin (0. 1 mg/kg) at 24 hr intervals for 5 days. Escalating Dose group infants will receive indomethacin (0. 2 mg/kg/dose) at 12 hr intervals for 2 doses, followed by indomethacin (0. 3 mg/kg/dose) at 12 hr interval for 2 doses, then Indomethacin (0. 4 mg/kg/dose) at 12 hr interval for 2 doses, increased to indomethacin (0. 5 mg/kg/dose) at 12 hour interval for 2 doses and finally indomethacin 0. 6 mg/kg/dose at 12 hourly interval for 2 doses. To keep the study blinded, the standard group will receive 5 extra doses of normal saline infusion of similar volume at 12 hrly intervals between the indomethacin schedules to match the Escalating dose Indomethacin Schedule. Daily Echo will be performed and if the Echo showed closure of PDA after 3 days of assigned treatment, no further indomethacin will be given in both the groups.

Minimum age: N/A. Maximum age: 4 Weeks. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Preterm infants with gestational age < 29 weeks and/or birth weight < 1251gm

- Presence of PDA after completion of first course of indomethacin

Exclusion Criteria:

- Infants with PDA dependent congenital heart disease

- Chromosomal or major congenital anomalies

- Infants in whom use of indomethacin is contraindicated.(i. e.infants with acute renal

failure,necrotizing enterocolitis,severe thrombocytopenia (platelet count < 60,000/ mm3) and evidence of clinical bleeding (pulmonary bleeding, severe intraventricular bleeding grade 3&4)

Amuchou S Soraisham, MD, DM, Phone: (403) 944-1615, Email: amuchou.soraisham@albertahealthservices.ca

Foothills Medical Centre, Calgary, Alberta T2N 2T9, Canada; Recruiting
Amuchou S Soraisham, MD,DM, Phone: (403) 944-1615, Email: amuchou.soraisham@albertahealthservices.ca
Harish Amin, MD,FRCPC, Sub-Investigator
Stacey Dalgleish, MN,NNP, Sub-Investigator
Nalini Singhal, MD,FRCPC, Sub-Investigator

Starting date: August 2008
Last updated: January 11, 2010