Antiviral Therapy for Influenza A H1N1 (SEA032)
The aims of this study are to characterise the clinical efficacy and virological clearance dynamics of orally administered oseltamivir in patients with influenza caused by novel influenza A(H1N1). This research will also contribute to enhancing research capacity in affected countries.
The objectives are to assess the:
- viral replication levels over time in affected patients
- antiviral efficacy of oral oseltamivir
- patterns and compartments of viral shedding, tissue distribution
- innate inflammatory response and relation to viral replication
- kinetics of antibody response
- antiviral sensitivity of influenza viruses at baseline and during oseltamivir treatment using in vitro and molecular methods
- pharmacokinetic characteristics of oseltamivir and oseltamivir carboxylate
- all cause in hospital mortality
- clinical and radiological features, disease course and outcome
- length of stay in hospital
- risk factors associated with development of severe disease and death
Influenza A Virus Infection
|Study Design:||Observational Model: Case-Only
Time Perspective: Prospective
|Official Title:||Antiviral Treatment in Adults and Children With Novel Influenza A (H1N1) Respiratory Tract Infection - a Clinical, Virological and Pharmacokinetic Study.|
- Viral clearance on Day 5 on all collected nasopharyngeal samples, assessed by RT PCR for new influenza A(H1N1) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
- Viral clearance on Day 1, 2, 3, 4, 5 (H1N1) on nose and throat swab, assessed by RT PCR. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Biospecimen Retention: Samples With DNA
Nasal swabs, throat swabs, nasopharyngeal aspirates, rectal swabs, urine, blood, will be obtained for virological analyses, according to the age group specific study schedules
|Study Start Date:||September 2009|
|Study Completion Date:||September 2010|
|Primary Completion Date:||August 2010 (Final data collection date for primary outcome measure)|
Any patient over 1 year of age who presents to a participating institution with confirmed influenza A and who meets the study inclusion/exclusion criteria may be approached for informed consent. Choice of antiviral is up to the study physician. Children aged 1-6 years and asthmatics should receive oseltamivir. The weight- and age-adjusted dosage used will be that approved for treatment of uncomplicated seasonal influenza, and doses will be administered twice daily for 5 days for patients with normal renal function. All patients who are clinical and/or virologic failures at day 5 will be treated for an additional 5 days of antivirals. After coming off antiviral therapy patients can be discharged at day 10 if deemed ready by study physicians and they are virologically negative.
During the course of treatment study evaluations will be performed to determine primary efficacy end points including viral clearance on Day 5 on all collected nasopharyngeal samples, assessed by RT PCR for novel H1N1 influenza AND no clinical features of clinical failure. Evaluations will also be performed to determine secondary viral, serological, clinical efficacy, safety and pharmacokinetic endpoints.
Patients will be followed up for up to 6 months after discharge for a clinical assessment, pulmonary function and outcome of pregnancy.
The protocol will be reviewed after 6 months from starting or after 100 patients with Influenza A are recruited.
|National Institute for Infectious and Tropical Diseases (NIITD), Viet Nam|
|Principal Investigator:||Jeremy Farrar, MD||Oxford University Clinical Research Unit Ho Chi Minh City Vietnam|