Clinical trial NCT00750581: An Escalating Dose Indomethacin for the Treatment of Persistent Patent Ductus Arteriosus (PDA) In Preterm Infants
Official title: An Escalating Dose Indomethacin for the Treatment of Persistent Patent Ductus Arteriosus (PDA) In Preterm Infants- A Randomized Pilot Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Patent Ductus Arteriosus
Keywords: Patent Ductus Arteriosus
Lead sponsor: University of Calgary
Sponsor class: OTHER
First posted: 2008-09-10
Enrollment: 9
Sex: ALL
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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)

Primary outcomes:
measure: Survival without PDA ligation at discharge
timeFrame: till the discharge from hospital
Secondary outcomes:
measure: PDA closure rate
timeFrame: after completion of indomethacin treatment
measure: Incidence of necrotizing enterocolitis, renal failure and bronchopulmonary dysplasia
timeFrame: till discharge from hospital
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
Study officials:
affiliation: University of Calgary
name: Amuchou S Soraisham, MD, DM
role: PRINCIPAL_INVESTIGATOR
References: