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

• Status: Terminated
• Trial end date: 2011-05-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Manitoba
• Collaborator: Hoffmann-La Roche
• Treatments: Oseltamivir

Criteria

Inclusion Criteria:

1. Patients age 12 and older and 45 kg or more

2. Suspected or confirmed influenza (Appendix A)

3. Requirement for ICU admission due to respiratory distress or critical illness defined as one of:

1. Inspired oxygen need of >50% for at least 4 hours (For FiO2 for non-intubated patients see Appendix B)

2. mechanical ventilation

3. Patient is receiving inotrope or vasopressor

4. 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

Exclusion Criteria:

1. Inability to obtain consent

2. Patients receiving more than two doses of 150 mg or higher oseltamivir in 36 hours before study entry

3. Patients having received more than 3 doses of 75 mg oseltamivir immediately in 36 hours before study entry

4. Age less than 12 years, or age <16 and weight less than 45 kg

5. Unlikely to absorb enteral study drug (e.g. patients with partial or complete mechanical bowel obstruction, intestinal ischemia, infarction, and short bowel syndrome)

6. Known allergy or hypersensitivity to oseltamivir

7. Pregnancy or breast feeding

8. Previous enrollment in current study

9. Concurrent involvement in an RCT examining an antiviral agent including other neuraminidase inhibitors, interferon-a and/or ribavirin

10. Chronic renal failure requiring chronic hemodialysis

11. Severe chronic liver disease (Child-Pugh Score 11-15)

12. Anticipated death within 24 hours as judged by attending physician or local PI

13. Patient carrying "do not intubate" order (a "no CPR" or "no defibrillate" or "no chest compressions" order alone is allowed)