Trial record 1 of 1 for:    NCT00799760
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Evaluation of Efficacity and Safety of Oseltamivir and Zanamivir (BIVIR)

This study has been terminated.
(Just Terminated for the end of the pandemia)
Sponsor:
Collaborators:
Hoffmann-La Roche
GlaxoSmithKline
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00799760
First received: November 28, 2008
Last updated: March 16, 2012
Last verified: November 2008
  Purpose

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.


Condition Intervention Phase
Gastric Influenza
Drug: oseltamivir + zanamivir
Drug: oseltamivir + zanamivir's placebo
Drug: oseltamivir's placebo + zanamivir
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • RT-PCR for influenza A virus in nasal secretion [ Time Frame: 2 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to resolution of influenzal illness Severity of illness [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • Severity of illness [ Time Frame: 14 Days ] [ Designated as safety issue: No ]
  • Adverse event (graded on a four -point scale:mild-moderate- severe-life threatening) [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
  • Compliance to antiviral treatment [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • Number of persons with influenza illness in households contact [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • Evaluation of restricted activity (requirement for additional health car) [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • Frequency of and need for antibiotic treatment of influenza (otitis media, bronchitis, sinusitis, and pneumonia ) [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • Frequency of resistance to antiviral drugs [ Time Frame: 14 days ] [ Designated as safety issue: No ]

Enrollment: 541
Study Start Date: December 2008
Study Completion Date: November 2010
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: active comparator arm

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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00799760

Locations
France
Centre Investigateur 155
Deulemont, France, 59000
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Hoffmann-La Roche
GlaxoSmithKline
Investigators
Principal Investigator: Catherine LEPORT, MD, PhD Assistance Publique - Hôpitaux de Paris
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT00799760     History of Changes
Other Study ID Numbers: P060209, AOM 08209, 2008-004026-16
Study First Received: November 28, 2008
Last Updated: March 16, 2012
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
influenza A
neuraminidase inhibitor
oseltamivir
zanamivir
treatment outcome
resistance
mutation
combination therapy
monotherapy
pandemic
primary care
randomized controlled trials
antiviral agent

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Zanamivir
Oseltamivir
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 26, 2014