Antiviral Therapy for Influenza A H1N1

Influenza A Virus Infection Clinical Trial

— SEA032  

Official title:

Antiviral Treatment in Adults and Children With Novel Influenza A (H1N1) Respiratory Tract Infection - a Clinical, Virological and Pharmacokinetic Study.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00985582
• Other study ID #: SEA032
• Status: Completed
• Phase: N/A
• First received: September 25, 2009
• Last updated: May 25, 2011
• Start date: September 2009
• Est. completion date: September 2010

Study information

• Verified date: May 2011
• Source: South East Asia Infectious Disease Clinical Research Network
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics CommitteeVietnam: Ministry of HealthThailand: Ethical Committee
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 181
• Est. completion date: September 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year and older

Eligibility

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

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Influenza A Virus Infection
• Influenza, Human
• Respiratory Tract Infections
• Virus Diseases

Locations

Country	Name	City	State
Vietnam	National Institute for Infectious and Tropical Diseases (NIITD), Viet Nam	Hanoi

Sponsors (2)

Lead Sponsor	Collaborator
South East Asia Infectious Disease Clinical Research Network	Wellcome Trust

Country where clinical trial is conducted

Vietnam, 

References & Publications (5)

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. Review. — View Citation

Ferraris O, Lina B. Mutations of neuraminidase implicated in neuraminidase inhibitors resistance. J Clin Virol. 2008 Jan;41(1):13-9. Epub 2007 Dec 11. Review. — View 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. Review. — View 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. Review. — View 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. Epub 2003 Jun 23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Viral clearance on Day 5 on all collected nasopharyngeal samples, assessed by RT PCR for new influenza A(H1N1)		12 months	Yes
Secondary	Viral clearance on Day 1, 2, 3, 4, 5 (H1N1) on nose and throat swab, assessed by RT PCR.		12 months	Yes