Trial Comparing High Versus Standard Dose Oseltamivir in Severe Influenza Infection in ICU

NCT01010087 | Terminated Phase 2 DMC

• 1 other identifier: 133312
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objectives: The primary objective of the trial is to compare the antiviral efficacy of a 10 day course of standard (75 mg bid) and high-dose (225 mg bid) oseltamivir (or equivalent doses in mild-moderate renal failure) in the treatment of severe influenza infections. The hypothesis is that high dose oseltamivir will increase the proportion of patients with negative reverse transcriptase (RT)-PCR detection of influenza viral RNA (and viral culture, at selected sites) at Day 5 post-treatment. An important secondary objective of the trial, which reflects the main clinical objective, is to determine the difference in the numbers of ventilator days between the standard-dose and high-dose groups

Conditions

Influenza A Virus

Keywords

patients admitted to ICU

Outcome Measures

Primary Outcomes (1)

• Negative reverse transcriptase (RT)-PCR detection of viral RNA in nasopharyngeal and tracheal aspirate (intubated) or oropharyngeal (non-intubated) samples at Day 5 among patients who require ICU admission due to respiratory distress.

  Day 5 on study

Secondary Outcomes (1)

• Ventilator days up to 60 d (main clinical endpoint),

  60 days

Study Arms (2)

Standard Oseltamivir dose 75 mg bid

ACTIVE COMPARATOR

Standard dosing

Drug: Oseltamivir

High Dose Oseltamivir arm 225mg bid

EXPERIMENTAL

High dose arm of the study

Drug: Oseltamivir

Interventions

Oseltamivir DRUG

standard (75 mg bid) or high-dose (225 mg bid) oseltamivir

Also known as: Tamiflu

High Dose Oseltamivir arm 225mg bid; Standard Oseltamivir dose 75 mg bid

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients age 12 and older and 45 kg or more
• Suspected or confirmed influenza (Appendix A)
• Requirement for ICU admission due to respiratory distress or critical illness defined as one of:
• Inspired oxygen need of \>50% for at least 4 hours (For FiO2 for non-intubated patients see Appendix B)
• mechanical ventilation
• Patient is receiving inotrope or vasopressor
• Negative b-HCG test or negative bedside urine test pending a confirmatory b-HCG test for pregnancy in women of childbearing age (12-60 years of age) will allow study entry

You may not qualify if:

• Inability to obtain consent
• Patients receiving more than two doses of 150 mg or higher oseltamivir in 36 hours before study entry
• Patients having received more than 3 doses of 75 mg oseltamivir immediately in 36 hours before study entry
• Age less than 12 years, or age \<16 and weight less than 45 kg
• Unlikely to absorb enteral study drug (e.g. patients with partial or complete mechanical bowel obstruction, intestinal ischemia, infarction, and short bowel syndrome)
• Known allergy or hypersensitivity to oseltamivir
• Pregnancy or breast feeding
• Previous enrollment in current study
• Concurrent involvement in an RCT examining an antiviral agent including other neuraminidase inhibitors, interferon-a and/or ribavirin
• Chronic renal failure requiring chronic hemodialysis
• Severe chronic liver disease (Child-Pugh Score 11-15)
• Anticipated death within 24 hours as judged by attending physician or local PI
• Patient carrying "do not intubate" order (a "no CPR" or "no defibrillate" or "no chest compressions" order alone is allowed)

Sponsors & Collaborators

• University of Manitoba: lead
• Hoffmann-La Roche: collaborator

Study Sites (1)

Winnipeg Regional Health Authority; Health Sciences Centre

Winnipeg, Manitoba, R3E 0Z3, Canada

Location

MeSH Terms

Interventions

Oseltamivir

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Anand Kumar, MD

  University of Manitoba

  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: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 5, 2009
• First Posted: November 9, 2009
• Study Start: November 1, 2009
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: June 10, 2011

Record last verified: 2011-06

Locations

CA (1)