Influenza A Virus Infection, Influenza B Virus Infection
Conditions
Keywords
Prevention or treatment of influenza in ventilated patients
Brief summary
This proposed pharmacokinetic study will test the hypothesis that in critically ill patients with respiratory failure requiring mechanical ventilation such as might be anticipated to be needed to treat patients with severe influenza pneumonia, oseltamivir administered enterally via nasogastric tube, with and without concomitant food or alimentation, will have similar oral bioavailability to that observed in ambulatory adults ill with influenza in whom oseltamivir therapy 75 mg BID is efficacious and well tolerated. Additionally, this experiment will test the hypothesis that increasing the dose (150 mg), with and without concomitant enteral feeding, will show a proportionate increase in bioavailability. Relative oral bioavailability will be assessed from plasma concentration vs. time over 12 hrs and urinary recovery of drug from 0 to 48 hrs after administration.
Detailed description
Not required
Interventions
The primary objective of this study is to demonstrate that the pharmacokinetics of oseltamivir, when given enterally to critically ill patients, in the standard treatment dose of 75 mg or double that dose, 150 mg, will yield a plasma concentration - versus - Time Area under the curve (AUC) similar to that observed in adults with influenza treated successfully with a dose of 75 mg, that the disposition characteristics are dose proportionate and are not altered by the concomitant administration of enteral feedings.
Sponsors
Hoffmann-La Roche
University of Manitoba
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* patients admitted to the Intensive Care Unit requiring mechanical ventilation due to respiratory failure * must be within the ages of 18-75 yrs
Exclusion criteria
* patients unable to have enteral feeding * intolerance to oseltamivir * pregnancy * gastrointestinal or malabsorptive disease * intestinal bypass surgery * diarrhea (\>2 loose bowel movements per day) * receipt of prokinetic medications (metoclopramide, domperidone, erythromycin) * severe liver disease (hepatocellular enzymes \> 3 times the upper limit of normal) * renal failure (Cockroft-Gault Creatinine Clearance \< 30 ml/min, Dialysis dependant) * cystic fibrosis * intoxication or drug overdose
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Oseltamivir administered enterally via nasogastric tube, with and without concomitant food or alimentation, will have similar oral bioavailability to that observed in ambulatory adults . | 13 months |
Secondary
| Measure | Time frame |
|---|---|
| Test the hypothesis that increasing the dose (150 mg), with and without concomitant enteral feeding, will show a proportionate increase in bioavailability. | 13 months |
Countries
Canada
Outcome results
None listed