Evaluation of Efficacity and Safety of Oseltamivir and Zanamivir

NCT00799760 | Terminated Phase 3 DMC

• 3 other identifiers: P060209AOM 082092008-004026-16
• Study Type: interventional
• Target: 541
• Locations: 1 country
• Sites: 1

Brief Summary

In order to prevent the high mortality due to an hypothetic pandemic caused by a newly emerging influenza A virus, antiviral drugs are seen as essential requirements for control of initial influenza outbreaks.Two antivirals are available for the treatment oseltamivir and zanamivir. Emergence of Oseltamivir resistance has been recently reported. . It appeared opportune to assess the efficacy and safety of biotherapy of neuraminidase inhibitors ,will be investigated by a randomized, placebo controlled, double blind study in France, during the next winter season . This study will be conducted in 300 centres of primary care with 900 adults with a virologically suspected influenza A infection. Individuals will be randomized to 1 of the 3 treatment groups: oseltamivir +zanamivir, or oseltamivir+placebo or placebo +zanamivir.The primary judgment criteria will be the proportion of patients with negative RT PCR negative in nasal secretions at Day 2.

Conditions

Gastric Influenza

Keywords

influenza A; neuraminidase inhibitor; oseltamivir; zanamivir; treatment outcome; resistance; mutation; combination therapy; monotherapy; pandemic; primary care; randomized controlled trials; antiviral agent

Outcome Measures

Primary Outcomes (1)

• RT-PCR for influenza A virus in nasal secretion

  2 days

Secondary Outcomes (8)

• Time to resolution of influenzal illness Severity of illness

  14 days

• Severity of illness

  14 Days

• Adverse event (graded on a four -point scale:mild-moderate- severe-life threatening)

  14 days

• Compliance to antiviral treatment

  14 days

• Number of persons with influenza illness in households contact

  14 days

Study Arms (3)

1

EXPERIMENTAL

oral oseltamivir 75mg twice daily + zanamivir 10 mg inhaled by mouth twice daily during 5 days

Drug: oseltamivir + zanamivir

2

ACTIVE COMPARATOR

oral oseltamivir 75mg twice daily+ placebo inhaled by mouth twice daily during 5 days

Drug: oseltamivir + zanamivir's placebo

3

ACTIVE COMPARATOR

oral placebo twice daily + zanamivir 10 mg inhaled by mouth twice daily during 5 day

Drug: oseltamivir's placebo + zanamivir

Interventions

oseltamivir + zanamivir DRUG

oral oseltamivir 75mg twice daily + zanamivir 10 mg inhaled by mouth twice daily during 5 days

Also known as: experimental Arm

1

oseltamivir + zanamivir's placebo DRUG

oral oseltamivir 75mg twice daily+ placebo inhaled by mouth twice daily during 5 day

Also known as: Active comparator Arm

2

oseltamivir's placebo + zanamivir DRUG

oral placebo twice daily + zanamivir 10 mg inhaled by mouth twice daily during 5 day

Also known as: active comparator arm

3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Influenza season declared
• Subjects aged\>18 years presenting within 36h documented of onset influenza illness
• Who have fever \>38°C
• who present at least on of the following respiratory symptoms( cough, sore throat, nasal symptoms)
• and one of the following constitutional symptoms(headache, myalgia, sweats and or chills or fatigue)
• positive rapid diagnostic test for influenza A
• who have giving written informed consent prior to enrollment
• able to complete a questionnaire.

You may not qualify if:

• Influenza Vaccination in the 12 months prior the beginning of the study
• Patient unable to use diskhaler of Zanamivir
• Asthma, Chronic bronchitis,
• Woman with a positive urine pregnancy test
• Clearance of creatinine\< 30 ml/min Chronic renal disease
• History of depression, psychiatric disorders
• oseltamivir or zanamivir hypersensibility
• patient treated by oseltamivir or zanamivir or amantadine 14 days before
• Non member of the social security or CMU

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Hoffmann-La Roche: collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

Centre Investigateur 155

Deûlémont, 59000, France

Location

Related Publications (4)

• Blanchon T, Mentre F, Charlois-Ou C, Dornic Q, Mosnier A, Bouscambert M, Carrat F, Duval X, Enouf V, Leport C; Bivir Study Group. Factors associated with clinical and virological response in patients treated with oseltamivir or zanamivir for influenza A during the 2008-2009 winter. Clin Microbiol Infect. 2013 Feb;19(2):196-203. doi: 10.1111/j.1469-0691.2011.03751.x. Epub 2012 Jan 20.

  PMID: 22264308 RESULT

• Galimard JE, Chevret S, Curis E, Resche-Rigon M. Heckman imputation models for binary or continuous MNAR outcomes and MAR predictors. BMC Med Res Methodol. 2018 Aug 31;18(1):90. doi: 10.1186/s12874-018-0547-1.

  PMID: 30170561 DERIVED

• Flicoteaux R, Protopopescu C, Tibi A, Blanchon T, Werf SV, Duval X, Mosnier A, Charlois-Ou C, Lina B, Leport C, Chevret S. Factors associated with non-persistence to oral and inhaled antiviral therapies for seasonal influenza: a secondary analysis of a double-blind, multicentre, randomised clinical trial. BMJ Open. 2017 Jul 10;7(7):e014546. doi: 10.1136/bmjopen-2016-014546.

  PMID: 28698321 DERIVED

• Duval X, van der Werf S, Blanchon T, Mosnier A, Bouscambert-Duchamp M, Tibi A, Enouf V, Charlois-Ou C, Vincent C, Andreoletti L, Tubach F, Lina B, Mentre F, Leport C; Bivir Study Group. Efficacy of oseltamivir-zanamivir combination compared to each monotherapy for seasonal influenza: a randomized placebo-controlled trial. PLoS Med. 2010 Nov 2;7(11):e1000362. doi: 10.1371/journal.pmed.1000362.

  PMID: 21072246 DERIVED

MeSH Terms

Interventions

Oseltamivir; Zanamivir

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Guanidines; Amidines; Sialic Acids; Neuraminic Acids; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Amino Sugars; Carbohydrates

Study Officials

• Catherine LEPORT, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2008
• First Posted: December 1, 2008
• Study Start: December 1, 2008
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2010
• Last Updated: March 19, 2012

Record last verified: 2008-11

Locations

FR (1)