Gastric InfluenzaPhase 3BIVIRNCT00799760
Evaluation of Efficacity and Safety of Oseltamivir and Zanamivir
A Phase 3 study testing oseltamivir + zanamivir in people with Gastric Influenza, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastric Influenza
- What is being tested?
- oseltamivir + zanamivir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 541 participants
- Where
- 1 siteFrance
- Study dates
- Dec 2008to Nov 2010
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- who have giving written informed consent prior to enrollment
- Patient examined before the inclusion
- able to complete a questionnaire.
Who cannot join
- 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
Show all 9Show fewer
- oseltamivir or zanamivir hypersensibility
- patient treated by oseltamivir or zanamivir or amantadine 14 days before
- Non member of the social security or CMU
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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)
- Conditions
- Gastric Influenza
- Being tested
- oseltamivir + zanamivir, oseltamivir + zanamivir's placebo, oseltamivir's placebo + zanamivir
- Keywords
- influenza A, neuraminidase inhibitor, oseltamivir, zanamivir, treatment outcome, resistance, mutation, combination therapy, monotherapy, pandemic, primary care, randomized controlled trials, antiviral agent
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
oseltamivir + zanamivirDrug
Also called experimental Arm
oral oseltamivir 75mg twice daily + zanamivir 10 mg inhaled by mouth twice daily during 5 days
oseltamivir + zanamivir's placeboDrug
Also called Active comparator Arm
oral oseltamivir 75mg twice daily+ placebo inhaled by mouth twice daily during 5 day
oseltamivir's placebo + zanamivirDrug
Also called active comparator arm
oral placebo twice daily + zanamivir 10 mg inhaled by mouth twice daily during 5 day
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | oral oseltamivir 75mg twice daily + zanamivir 10 mg inhaled by mouth twice daily during 5 days Receives: Drug: oseltamivir + zanamivir |
| 2 | Active comparator | oral oseltamivir 75mg twice daily+ placebo inhaled by mouth twice daily during 5 days Receives: Drug: oseltamivir + zanamivir's placebo |
| 3 | Active comparator | oral placebo twice daily + zanamivir 10 mg inhaled by mouth twice daily during 5 day Receives: Drug: oseltamivir's placebo + zanamivir |
What is being measured
The primary outcome is the main question the study is designed to answer.
RT-PCR for influenza A virus in nasal secretion
Measured: 2 days
Secondary outcomes (8)
Time to resolution of influenzal illness Severity of illness
Measured: 14 days
Severity of illness
Measured: 14 Days
Adverse event (graded on a four -point scale:mild-moderate- severe-life threatening)
Measured: 14 days
Compliance to antiviral treatment
Measured: 14 days
Number of persons with influenza illness in households contact
Measured: 14 days
Evaluation of restricted activity (requirement for additional health car)
Measured: 14 days
Frequency of and need for antibiotic treatment of influenza (otitis media, bronchitis, sinusitis, and pneumonia )
Measured: 14 days
Frequency of resistance to antiviral drugs
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2008 (estimated)
- Study startDec 2008
- Primary completionNov 2009
- Study completionNov 2010
Why it stopped: Just Terminated for the end of the pandemia
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Gastric InfluenzaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 541 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche, GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Catherine LEPORT, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00799760
- Sponsor's protocol ID
- P060209
- Other IDs
- AOM 08209, 2008-004026-16, 2008
- Acronym
- BIVIR
- Status last verified
- Nov 2008
- First submitted
- 28 Nov 2008
- Last updated
- 19 Mar 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 22264308Galimard 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.
PubMed 30170561Flicoteaux 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.
PubMed 28698321Duval 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.
PubMed 21072246
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00799760
- Acronym / sponsor ID
- BIVIR / P060209
- Conditions
- Gastric Influenza
- Keywords
- influenza A, neuraminidase inhibitor, oseltamivir, zanamivir, treatment outcome, resistance, mutation, combination therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Just Terminated for the end of the pandemia
- Enrolment
- 541 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche, GlaxoSmithKline
- Study start
- Dec 2008
- Primary completion
- Nov 2009 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 1 Dec 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: oseltamivir + zanamiviroral oseltamivir 75mg twice daily + zanamivir 10 mg inhaled by mouth twice daily during 5 days |
| 2 | Active comparator | Drug: oseltamivir + zanamivir's placebooral oseltamivir 75mg twice daily+ placebo inhaled by mouth twice daily during 5 days |
| 3 | Active comparator | Drug: oseltamivir's placebo + zanamiviroral placebo twice daily + zanamivir 10 mg inhaled by mouth twice daily during 5 day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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)
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| oseltamivir + zanamivirAlso: experimental Armoral oseltamivir 75mg twice daily + zanamivir 10 mg inhaled by mouth twice daily during 5 days | Drug | 1 |
| oseltamivir + zanamivir's placeboAlso: Active comparator Armoral oseltamivir 75mg twice daily+ placebo inhaled by mouth twice daily during 5 day | Drug | 2 |
| oseltamivir's placebo + zanamivirAlso: active comparator armoral placebo twice daily + zanamivir 10 mg inhaled by mouth twice daily during 5 day | Drug | 3 |
Primary outcome
RT-PCR for influenza A virus in nasal secretion
Time frame: 2 days
8 secondary outcomes
Time to resolution of influenzal illness Severity of illness
Time frame: 14 days
Severity of illness
Time frame: 14 Days
Adverse event (graded on a four -point scale:mild-moderate- severe-life threatening)
Time frame: 14 days
Compliance to antiviral treatment
Time frame: 14 days
Number of persons with influenza illness in households contact
Time frame: 14 days
Evaluation of restricted activity (requirement for additional health car)
Time frame: 14 days
Frequency of and need for antibiotic treatment of influenza (otitis media, bronchitis, sinusitis, and pneumonia )
Time frame: 14 days
Frequency of resistance to antiviral drugs
Time frame: 14 days
Results and safety
The study was stopped early (reason given: Just Terminated for the end of the pandemia). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2012.
- Results publication: PubMed 22264308Blanchon 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.
- Derived from this study: PubMed 30170561Galimard 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.
- Derived from this study: PubMed 28698321Flicoteaux 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.
- Derived from this study: PubMed 21072246Duval 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Catherine LEPORT, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing oseltamivir + zanamivir in people with Gastric Influenza, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Just Terminated for the end of the pandemia). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
RT-PCR for influenza A virus in nasal secretion (time frame: 2 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00799760, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2012.