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

NCT00750581 | Terminated Phase 2 DMC

• 1 other identifier: RT734510
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Patent Ductus Arteriosus

Keywords

Patent Ductus Arteriosus

Outcome Measures

Primary Outcomes (1)

• Survival without PDA ligation at discharge

  till the discharge from hospital

Secondary Outcomes (2)

• PDA closure rate

  after completion of indomethacin treatment

• Incidence of necrotizing enterocolitis, renal failure and bronchopulmonary dysplasia

  till discharge from hospital

Study Arms (2)

Standard dose group

PLACEBO COMPARATOR

The 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

Drug: Indomethacin

Escalating dose group

ACTIVE COMPARATOR

The 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

Drug: Indomethacin

Interventions

Indomethacin DRUG

Infants randomized to Escalating Dose group 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.

Also known as: indocid

Escalating dose group; Standard dose group

Eligibility Criteria

• Age: Up to 4 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Preterm infants with gestational age \< 29 weeks and/or birth weight \< 1251gm
• Presence of PDA after completion of first course of indomethacin

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Calgary: lead

Study Sites (1)

Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

Location

MeSH Terms

Conditions

Ductus Arteriosus, Patent

Interventions

Indomethacin

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Amuchou S Soraisham, MD, DM

  University of Calgary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 8, 2008
• First Posted: September 10, 2008
• Study Start: August 1, 2008
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: August 18, 2016

Record last verified: 2016-08

Locations

CA (1)