Clinical trial NCT00985582: Antiviral Therapy for Influenza A H1N1
Official title: Antiviral Treatment in Adults and Children With Novel Influenza A (H1N1) Respiratory Tract Infection - a Clinical, Virological and Pharmacokinetic Study.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Influenza A Virus Infection
Keywords: Influenza A Virus (H1N1)
Lead sponsor: South East Asia Infectious Disease Clinical Research Network
Sponsor class: NETWORK
Collaborators: name: Wellcome Trust
First posted: 2009-09-28
Enrollment: 181
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: This is a single arm clinical and virological study assessing the use of oral oseltamivir or other agents in the treatment of patients with novel influenza A(H1N1) infection.

Any patient over 1 year of age with confirmed novel influenza A(H1N1) in whom appropriate informed consent to collect data and samples is obtained. The protocol will be reviewed after 6 months from starting or after 100 patients with new influenza A(H1N1) are recruited.

Brief summary: 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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Adults, including pregnant and breast feeding women, and Children aged ≥ 12 months when first seen with an acute febrile respiratory tract illness (ARI) of any severity and influenza A, virologically proven on a respiratory specimen according to hospital procedure, which is suspected to be novel influenza A(H1N1)
* A positive influenza A H1 swine screening reverse transcriptase polymerase chain reaction (RT PCR) or conventional PCR assay on one respiratory specimen : NPA, NP swab, nasal wash, nasal swab and throat swab
* Underlying illnesses including HIV
* Prescribed oseltamivir prior to presentation

Exclusion Criteria:

* Lack of informed consent

Primary outcomes:
measure: Viral clearance on Day 5 on all collected nasopharyngeal samples, assessed by RT PCR for new influenza A(H1N1)
timeFrame: 12 months
Secondary outcomes:
measure: Viral clearance on Day 1, 2, 3, 4, 5 (H1N1) on nose and throat swab, assessed by RT PCR.
timeFrame: 12 months
Other outcomes:
Locations:
city: Hanoi
country: Vietnam
facility: National Institute for Infectious and Tropical Diseases (NIITD), Viet Nam
Study officials:
affiliation: Oxford University Clinical Research Unit Ho Chi Minh City Vietnam
name: Jeremy Farrar, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lackenby A, Thompson CI, Democratis J. The potential impact of neuraminidase inhibitor resistant influenza. Curr Opin Infect Dis. 2008 Dec;21(6):626-38. doi: 10.1097/QCO.0b013e3283199797.
citation: Ferraris O, Lina B. Mutations of neuraminidase implicated in neuraminidase inhibitors resistance. J Clin Virol. 2008 Jan;41(1):13-9. doi: 10.1016/j.jcv.2007.10.020. Epub 2007 Dec 11.
citation: Shiraishi K, Mitamura K, Sakai-Tagawa Y, Goto H, Sugaya N, Kawaoka Y. High frequency of resistant viruses harboring different mutations in amantadine-treated children with influenza. J Infect Dis. 2003 Jul 1;188(1):57-61. doi: 10.1086/375799. Epub 2003 Jun 23.
citation: Hurt AC, Ho HT, Barr I. Resistance to anti-influenza drugs: adamantanes and neuraminidase inhibitors. Expert Rev Anti Infect Ther. 2006 Oct;4(5):795-805. doi: 10.1586/14787210.4.5.795.
citation: Dutkowski R, Thakrar B, Froehlich E, Suter P, Oo C, Ward P. Safety and pharmacology of oseltamivir in clinical use. Drug Saf. 2003;26(11):787-801. doi: 10.2165/00002018-200326110-00004.