MedPath

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

Phase 2
Terminated
Conditions
Patent Ductus Arteriosus
Interventions
Registration Number
NCT00750581
Lead Sponsor
University of Calgary
Brief Summary

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.

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
9
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Standard dose groupIndomethacinThe infants randomized to the standard dose group will receive indomethacin (0.1 mg/kg) at 24 hr intervals for 5 days. These infants will also 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
Escalating dose groupIndomethacinThe infants randomized to the Escalating dose group will receive indomethacin started at 0.2 mg/kg/dose every 12 hours for 2 doses with stepwise increment in indomethacin dose by 0.1 mg/kg/dose every 24 hours upto maximum dose of 0.6 mg/kg/dose
Primary Outcome Measures
NameTimeMethod
Survival without PDA ligation at dischargetill the discharge from hospital
Secondary Outcome Measures
NameTimeMethod
PDA closure rateafter completion of indomethacin treatment
Incidence of necrotizing enterocolitis, renal failure and bronchopulmonary dysplasiatill discharge from hospital

Trial Locations

Locations (1)

Foothills Medical Centre

🇨🇦

Calgary, Alberta, Canada

Foothills Medical Centre
🇨🇦Calgary, Alberta, Canada

MedPath

Empowering clinical research with data-driven insights and AI-powered tools.

© 2025 MedPath, Inc. All rights reserved.