A Study on Higher-dose Oseltamivir Treatment's Impact on Viral Clearance and Clinical Recovery in Adults Hospitalized With Influenza

Influenza Clinical Trial

Official title:

Initiating Oseltamivir in Adults Hospitalized With Influenza -- a Study on the Impact of Virological Clearance and Clinical Recovery for Higher-dose Treatment Started Within 96 Hours

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01052961
• Other study ID #: CUHK 7010015, MV22926
• Status: Completed
• Phase: Phase 4
• First received: January 19, 2010
• Last updated: July 19, 2012
• Start date: January 2010
• Est. completion date: June 2012

Study information

• Verified date: July 2012
• Source: Chinese University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Health authority: Hong Kong: Joint CUHK-NTEC Clinical Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

Adult patients hospitalized with influenza have higher viral loads and more severe illnesses. Thus more aggressive treatment approaches (e.g. higher dose oseltamivir) have been suggested to treat patients suffering from severe influenza infection.

The investigators plan to investigate the impact of higher-dose oseltamivir (150 mg b.d.) treatment on viral clearance and clinical recovery in adult patients hospitalized for severe influenza. Such information may lead to optimization of the management strategy used for these patients.

Description:

• The investigators plan to study the impact of higher-dose oseltamivir (150 mg b.d.) treatment on rate of viral load decline and RNA negativity (in nasal and throat swabs, assessed by quantitative RT-PCR assay) and time to clinical recovery in adult patients hospitalized for severe influenza.

• Patients who received intervention (oseltamivir 150 mg b.d. for 5 days) will be compared to those in the non-intervention arm (patients may receive oseltamivir treatment at 75 mg b.d. for 5 days, decided by their managing physicians) in the two respective study sites. Viral load changes and viral clearance will be compared. Clinical progress and time to symptom recovery will be reported. The protocol will be crossed-over to the other site at a defined time frame.

• oseltamivir 150 mg b.d. has been shown to be safe and well-tolerated in earlier clinical trials

• higher-dose treatment has been suggested by health authorities (e.g. WHO) to treat severe influenza infection/pneumonia.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 157
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• confirmed influenza A (H1N1, H3N2) or B infection by IFA or RT-PCR, with a compatible clinical illness

• presented within 96 hours from symptom onset

• age >/= 18 years

Exclusion Criteria:

• lack of consent

• suspected avian influenza

• patients who have received antivirals against influenza prior to admission

• suspected or confirmed oseltamivir resistance

• pre-existing renal impairment, with creatinine clearance <40 ml/min

• pre-existing hepatic failure

• participation in a clinical study involving experimental medication in the past 4 weeks

• pregnant women, or who are attempting to become pregnant, or who are breast feeding.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Influenza
• Influenza, Human
• Respiratory Tract Infections

Intervention

Drug:
• Oseltamivir
oseltamivir 150 mg bd for 5 days

Locations

Country	Name	City	State
Hong Kong	The Chinese University of Hong Kong, Prince of Wales Hospital and Alice Ho Miu Ling Nethersole Hospital	Hong Kong	Hksar

Sponsors (2)

Lead Sponsor	Collaborator
Chinese University of Hong Kong	Hoffmann-La Roche

Country where clinical trial is conducted

Hong Kong, 

References & Publications (7)

Lee N, Chan PK, Choi KW, Lui G, Wong B, Cockram CS, Hui DS, Lai R, Tang JW, Sung JJ. Factors associated with early hospital discharge of adult influenza patients. Antivir Ther. 2007;12(4):501-8. — View Citation

Lee N, Chan PK, Hui DS, Rainer TH, Wong E, Choi KW, Lui GC, Wong BC, Wong RY, Lam WY, Chu IM, Lai RW, Cockram CS, Sung JJ. Viral loads and duration of viral shedding in adult patients hospitalized with influenza. J Infect Dis. 2009 Aug 15;200(4):492-500. doi: 10.1086/600383. — View Citation

Lee N, Cockram CS, Chan PK, Hui DS, Choi KW, Sung JJ. Antiviral treatment for patients hospitalized with severe influenza infection may affect clinical outcomes. Clin Infect Dis. 2008 Apr 15;46(8):1323-4. doi: 10.1086/533477. — View Citation

Lee N, Wong CK, Chan PK, Lun SW, Lui G, Wong B, Hui DS, Lam CW, Cockram CS, Choi KW, Yeung AC, Tang JW, Sung JJ. Hypercytokinemia and hyperactivation of phospho-p38 mitogen-activated protein kinase in severe human influenza A virus infection. Clin Infect Dis. 2007 Sep 15;45(6):723-31. Epub 2007 Aug 8. — View Citation

Nicholson KG, Aoki FY, Osterhaus AD, Trottier S, Carewicz O, Mercier CH, Rode A, Kinnersley N, Ward P. Efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. Neuraminidase Inhibitor Flu Treatment Investigator Group. Lancet. 2000 May 27;355(9218):1845-50. Erratum in: Lancet 2000 Nov 25;356(9244):1856. — View Citation

Treanor JJ, Hayden FG, Vrooman PS, Barbarash R, Bettis R, Riff D, Singh S, Kinnersley N, Ward P, Mills RG. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. US Oral Neuraminidase Study Group. JAMA. 2000 Feb 23;283(8):1016-24. — View Citation

World Health Organization. Clinical management of human infection with pandemic (H1N1) 2009: revised guidance. Available at: http://www.who.int/csr/resources/publications/swineflu/clinical_management_h1n1.pdf. Last accessed on 1st Dec, 2009

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	rate of influenza virus load decline and viral RNA negativity upon receiving 5 days of study treatment		during and upon completion of the 5-day study treatment	No
Secondary	time to clinical recovery (including symptoms, vital signs, hospital discharge)		during and upon completion of the 5-day study treatment	No