Evaluation of Efficacity and Safety of Oseltamivir and Zanamivir (BIVIR)

March 16, 2012 updated by: Assistance Publique - Hôpitaux de Paris

Evaluation of Combination Therapy With Oseltamivir and Zanamivir Versus Monotherapy in the Treatment of Virologically Confirmed Influenza in Primary Care a Randomises Double Blind Controlled Trial Study

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

In the near future, a pandemic caused by a newly emerging influenza A virus has been predicted by the WHO. In order to prevent the high mortality due to the pandemic, antiviral drugs are seen as essential requirements for control of initial influenza outbreaks.

Zanamivir (GSK) and Oseltamivir (Roche) are stockpiled by the French government in the setting of pre-pandemic plan. In France, Zanamivir and Oseltamivir are both registered for the prophylactic and therapeutic use against influenza A.

Previous studies have shown that neuraminidase inhibitors (oseltamivir and zanamivir, based treatment) are associated with shorter illness duration and resulted in significant decrease of viral load in the nasal secretions.

In Winter season 2007-2008 the presence of oseltamivir-resistant viruses circulating in the community in several European countries is in marked contrast to the previous winter seasons, when oseltamivir resistance was detected in <1% of circulating strains from . Patients infected by viruses with neuraminidases carrying these mutations, didn't present unusual disease syndromes.

Although zanamivir and oseltamivir are both issued from the same class ,a combination of these two neuraminidase inhibitors could reduce the duration and severity of acute influenza and the incidence of secondary complications, reduce the spread of influenza, and the frequency of neuraminidase inhibitors mutations. An evaluation of the combination of oseltamivir and zanamivir versus zanamivir with placebo versus oseltamivir associated with placebo in the treatment of a virologically suspected influenza in primary care will be investigated in a randomised double blind placebo controlled trial study in France during the winter season 2008-2009.

Primary outcome measure:

Evaluate viral efficacy after 2 days of biotherapy oseltamivir and zanamivir versus zanamivir with placebo versus oseltamivir associated with placebo.

Patients and methods:

Randomised double blind, placebo controlled multicenter trial conducted during the influenza season 2008-2009 Arm 1: oral oseltamivir 75mg twice daily + zanamivir 10 mg inhaled by mouth twice daily during 5 days Arm 2: oral oseltamivir 75mg twice daily+ placebo inhaled by mouth twice daily during 5 days Arm 3: oral placebo twice daily + zanamivir 10 mg inhaled by mouth twice daily during 5 days.

Schedule:

D0: rapid test diagnostic for influenza A urine pregnancy test for women inclusion /randomisation initiation of treatment D2:nasal sample for influenza RNA RTPCR D5:End of treatment D7:medical evaluation (follow up evaluation) D14:nurse call (clinical evaluation)

Study Type

Interventional

Enrollment (Actual)

541

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Deulemont, France, 59000
        • Centre Investigateur 155

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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
  • Patient examined before the inclusion
  • able to complete a questionnaire.

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
oral oseltamivir 75mg twice daily + zanamivir 10 mg inhaled by mouth twice daily during 5 days
Drug: oseltamivir + zanamivir
oral oseltamivir 75mg twice daily + zanamivir 10 mg inhaled by mouth twice daily during 5 days
Other Names:
  • experimental Arm
Active Comparator: 2
oral oseltamivir 75mg twice daily+ placebo inhaled by mouth twice daily during 5 days
Drug: oseltamivir + zanamivir's placebo
oral oseltamivir 75mg twice daily+ placebo inhaled by mouth twice daily during 5 day
Other Names:
  • Active comparator Arm
Active Comparator: 3
oral placebo twice daily + zanamivir 10 mg inhaled by mouth twice daily during 5 day
Drug: oseltamivir's placebo + zanamivir
oral placebo twice daily + zanamivir 10 mg inhaled by mouth twice daily during 5 day
Other Names:
  • active comparator arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
RT-PCR for influenza A virus in nasal secretion
Time Frame: 2 days
2 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Time to resolution of influenzal illness Severity of illness
Time Frame: 14 days
14 days
Severity of illness
Time Frame: 14 Days
14 Days
Adverse event (graded on a four -point scale:mild-moderate- severe-life threatening)
Time Frame: 14 days
14 days
Compliance to antiviral treatment
Time Frame: 14 days
14 days
Number of persons with influenza illness in households contact
Time Frame: 14 days
14 days
Evaluation of restricted activity (requirement for additional health car)
Time Frame: 14 days
14 days
Frequency of and need for antibiotic treatment of influenza (otitis media, bronchitis, sinusitis, and pneumonia )
Time Frame: 14 days
14 days
Frequency of resistance to antiviral drugs
Time Frame: 14 days
14 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

GlaxoSmithKline
Hoffmann-La Roche

Investigators

  • Principal Investigator: Catherine LEPORT, MD, PhD, Assistance Publique - Hopitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2008

Primary Completion (Actual)

November 1, 2009

Study Completion (Actual)

November 1, 2010

Study Registration Dates

First Submitted

November 28, 2008

First Submitted That Met QC Criteria

November 28, 2008

First Posted (Estimate)

December 1, 2008

Study Record Updates

Last Update Posted (Estimate)

March 19, 2012

Last Update Submitted That Met QC Criteria

March 16, 2012

Last Verified

November 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P060209
  • AOM 08209 (Other Identifier: French Ministry)
  • 2008-004026-16 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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