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

Sponsored by:	University of Calgary
Information provided by:	University of Calgary
ClinicalTrials.gov Identifier:	NCT00750581

Purpose

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.

Condition	Intervention	Phase
Patent Ductus Arteriosus	Drug: Indomethacin	Phase II Phase III

Drug Information available for: Indomethacin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	An Escalating Dose Indomethacin for the Treatment of Persistent Patent Ductus Arteriosus (PDA) In Preterm Infants- A Randomized Pilot Study

Further study details as provided by University of Calgary:

Primary Outcome Measures:

Survival without PDA ligation at discharge [ Time Frame: till the discharge from hospital ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

PDA closure rate [ Time Frame: after completion of indomethacin treatment ] [ Designated as safety issue: Yes ]
Incidence of necrotizing enterocolitis, renal failure and bronchopulmonary dysplasia [ Time Frame: till discharge from hospital ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	30
Study Start Date:	August 2008
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Standard dose group: Active 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 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.

Arms

Assigned Interventions

Standard dose group: Active 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

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.

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

Ages Eligible for Study:	up to 4 Weeks
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00750581

Contacts

Contact: Amuchou S Soraisham, MD, DM

(403) 944-1615

amuchou.soraisham@calgaryhealthregion.ca

Locations

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

Sponsors and Collaborators

University of Calgary

Investigators

Principal Investigator:

Amuchou S Soraisham, MD, DM

University of Calgary

More Information

Responsible Party:	University of Calgary ( Amuchou Soraisham )
Study ID Numbers:	RT734510
Study First Received:	September 8, 2008
Last Updated:	September 8, 2008
ClinicalTrials.gov Identifier:	NCT00750581
Health Authority:	Canada: Health Canada

Keywords provided by University of Calgary:

Patent Ductus Arteriosus

Study placed in the following topic categories:

Heart Diseases
Cardiovascular Abnormalities
Indomethacin
Patent ductus arteriosus

Congenital Abnormalities
Heart Defects, Congenital
Ductus Arteriosus, Patent

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Cardiovascular Agents
Reproductive Control Agents
Gout Suppressants
Pharmacologic Actions
Tocolytic Agents

Sensory System Agents
Analgesics, Non-Narcotic
Therapeutic Uses
Cardiovascular Diseases
Anti-Inflammatory Agents, Non-Steroidal
Peripheral Nervous System Agents
Analgesics
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009