Influenza A InfectionPhase 2CombinaNCT00830323
Efficacy and Safety of Combination Therapies With Oseltamivir & Zanamivir or Oseltamivir & Amantadine Versus Oseltamivir Monotherapy in the Treatment of Seasonal Influenza A Infection
A Phase 2 study testing oseltamivir + zanamivir, oseltamivir+ amantadine and oseltamivir in people with Influenza A Infection, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
Neuraminidase inhibitors (NAI) are effective anti-influenza antiviral treatment. During their use in experimentally infected patients, it has been shown that the viral load detected in the nasal fluid is decreasing significantly faster than in non treated patients. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Influenza A Infection
- What is being tested?
- oseltamivir + zanamivir, oseltamivir+ amantadine and oseltamivir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteFrance
- Study dates
- Jan 2009to Aug 2009
- Phase
- Phase 2
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Influenza season declared
- Subjects aged>18 years and < 65 years presenting within 36h documented of onset influenza illness
- Who have fever >38°C
- Who present at least one 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
- Primary care follow up
Who cannot join
- Influenza Vaccination in the 12 months prior the beginning of the study
- Asthma, Chronic bronchitis
- Woman with a positive urine pregnancy test
- Active breast feeding
- Woman without contraception
- Clearance of creatinine< 30 ml/min Chronic renal disease
Show all 10Show fewer
- History of depression, psychiatric disorders, epilepsy
- Patients receiving cortocosteroids, immunosuppressants or antipsychotic antiemetic drugs
- Known oseltamivir or zanamivir hypersensibility
- Non member of the social security or CMU
Trial locations and contacts
1 site in 1 country.
About this study
Neuraminidase inhibitors (NAI) are effective anti-influenza antiviral treatment. During their use in experimentally infected patients, it has been shown that the viral load detected in the nasal fluid is decreasing significantly faster than in non treated patients. During clinical practice, the emergence of NAI-resistant strains has been observed. These strains remain rare, but their emergence seemed to be related to the mis-use of the NAI products (insufficient duration or dosage). This observation as well as the detection of NAI-resistant viruses in the community raises concerns about putative emergence of resistant clones in the specific context of a pandemic, when the use of NAI will be very large in the aim of reducing transmission, and subsequently the impact of the emerging virus.
In this context, it is important to determine the putative interest of alternative strategies.
Read more
Although zanamivir and oseltamivir are both issued from the same class , this combination may lead to a more rapid viral clearance in the infected cases, and to a reduction in the emergence of resistant sub-clones, and alternatively, might lead to a competitive inhibition. The evaluation of these combinations needs to be conducted in vivo.
Among available anti influenza antivirals, M2 blockers have been previously used. Although their efficacy against A H5N1 remains to be ascertained, their use in combination with NAI should also be evaluated in the context of a preparation for a possible pandemic and determination of the stockpile.
Therefore, the evaluation of combination therapies in the treatment of a virologically suspected influenza will be investigated in primary care during the winter season 2008-2009.
Read the detailed description
Study Schedule:
- Patient's follow up: 7 days with 10 visits V1, V2, V3, V4, V5 every 12 hours V6, V7, V8, V9, V10 every 24 hours
- V1: conducted by the GP rapid test diagnostic for influenza A, urine pregnancy test for women, inclusion /randomisation, nasal sample, initiation of treatment.
- V2 to V9: conducted by a nurse at the patient's home; nasal sample, symptoms scoring, safety assessment (side effects)
- V 10: conducted by GP; medical evaluation (follow up evaluation)
- Conditions
- Influenza A Infection
- Being tested
- oseltamivir + zanamivir, oseltamivir+ amantadine, oseltamivir
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
oseltamivir + zanamivirDrug
oseltamivir (75mg bd for 5 days, oral) zanamivir (5mg bd for 5 days, inhaled by mouth)
oseltamivir+ amantadineDrug
oseltamivir (75mg bd for 5 days, oral) + amantadine (100mg bd for 5 days, oral)
oseltamivirDrug
oseltamivir (75mg bd for 5 days, oral)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: oseltamivir + zanamivir |
| Arm 2 | Experimental | Not described Receives: Drug: oseltamivir+ amantadine |
| Arm 3 | Active comparator | Not described Receives: Drug: oseltamivir |
What is being measured
The primary outcome is the main question the study is designed to answer.
describe the antiviral efficacy in the 3 arms in the treatment of seasonal influenza infection as assessed by negative viral detection in nose swabs at the fifth swab [H48±3]
Measured: 48 hours
Describe the antiviral efficacy in 3 arms in the treatment of seasonal influenza infection as assessed by negativity of RT-PCR for viral RNA in nose and throat swabs at the 5th swab [H48±3] and at the 7th swab [H84±3].
Measured: 84 hours
Secondary outcomes (5)
Describe the antiviral efficacy in combination therapy arms (1,2) and in monotherapy arm (3) in the treatment of seasonal influenza infection as assessed by time to sustained negativity of RT-PCR for viral RNA or viral culture in any sample.
Measured: 168 hours
Assess viral replication dynamics (duration and level of viral replication) in the respiratory tract in the combination and standard-dose cohorts.
Measured: 168 hours
Assess the frequency, genetic basis, and duration of antiviral resistance to each arm during and after therapy
Measured: 168 hours
Describe the time to alleviation of illness in the 3 arms defined as the time from the beginning of the study treatment to the time that 7 typical key symptoms of natural influenza had reduced to absent or mi
Measured: 168 hours
Describe the tolerability of combination and in standard-dose arms as assessed by clinical adverse events that are possibly or probably related to each single agent (Incidence and duration)
Measured: 168 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2009 (estimated)
- Study startJan 2009
- Primary completionAug 2009 (estimated)
- Study completionAug 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Influenza A InfectionStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Investigators
- BRUNO LINA, MD,PhD, Principal investigator, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00830323
- Sponsor's protocol ID
- 2008-517
- Acronym
- Combina
- Status last verified
- Oct 2009
- First submitted
- 26 Jan 2009
- Last updated
- 30 Sep 2010
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Combination Therapies With Oseltamivir & Zanamivir or Oseltamivir & Amantadine Versus Oseltamivir Monotherapy in the Treatment of Seasonal Influenza A Infection
- ClinicalTrials.gov ID
- NCT00830323
- Acronym / sponsor ID
- Combina / 2008-517
- Conditions
- Influenza A Infection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- Jan 2009
- Primary completion
- Aug 2009 (estimated)
- Study completion
- Aug 2009 (estimated)
- First posted
- 27 Jan 2009 (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.
Neuraminidase inhibitors (NAI) are effective anti-influenza antiviral treatment. During their use in experimentally infected patients, it has been shown that the viral load detected in the nasal fluid is decreasing significantly faster than in non treated patients. During clinical practice, the emergence of NAI-resistant strains has been observed. These strains remain rare, but their emergence seemed to be related to the mis-use of the NAI products (insufficient duration or dosage). This observation as well as the detection of NAI-resistant viruses in the community raises concerns about putative emergence of resistant clones in the specific context of a pandemic, when the use of NAI will be very large in the aim of reducing transmission, and subsequently the impact of the emerging virus.
In this context, it is important to determine the putative interest of alternative strategies.
Although zanamivir and oseltamivir are both issued from the same class , this combination may lead to a more rapid viral clearance in the infected cases, and to a reduction in the emergence of resistant sub-clones, and alternatively, might lead to a competitive inhibition. The evaluation of these combinations needs to be conducted in vivo.
Among available anti influenza antivirals, M2 blockers have been previously used. Although their efficacy against A H5N1 remains to be ascertained, their use in combination with NAI should also be evaluated in the context of a preparation for a possible pandemic and determination of the stockpile.
Therefore, the evaluation of combination therapies in the treatment of a virologically suspected influenza will be investigated in primary care during the winter season 2008-2009.
Detailed description
Study Schedule:
- Patient's follow up: 7 days with 10 visits V1, V2, V3, V4, V5 every 12 hours V6, V7, V8, V9, V10 every 24 hours
- V1: conducted by the GP rapid test diagnostic for influenza A, urine pregnancy test for women, inclusion /randomisation, nasal sample, initiation of treatment.
- V2 to V9: conducted by a nurse at the patient's home; nasal sample, symptoms scoring, safety assessment (side effects)
- V 10: conducted by GP; medical evaluation (follow up evaluation)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: oseltamivir + zanamivir |
| Arm 2 | Experimental | Drug: oseltamivir+ amantadine |
| Arm 3 | Active comparator | Drug: oseltamivir |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Influenza season declared
- Subjects aged>18 years and < 65 years presenting within 36h documented of onset influenza illness
- Who have fever >38°C
- Who present at least one 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
Key exclusion criteria (10 listed)
- Influenza Vaccination in the 12 months prior the beginning of the study
- Asthma, Chronic bronchitis
- Woman with a positive urine pregnancy test
- Active breast feeding
- Woman without contraception
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 + zanamiviroseltamivir (75mg bd for 5 days, oral) zanamivir (5mg bd for 5 days, inhaled by mouth) | Drug | 1 |
| oseltamivir+ amantadineoseltamivir (75mg bd for 5 days, oral) + amantadine (100mg bd for 5 days, oral) | Drug | Arm 2 |
| oseltamiviroseltamivir (75mg bd for 5 days, oral) | Drug | Arm 3 |
Primary outcome
describe the antiviral efficacy in the 3 arms in the treatment of seasonal influenza infection as assessed by negative viral detection in nose swabs at the fifth swab [H48±3]
Time frame: 48 hours
Describe the antiviral efficacy in 3 arms in the treatment of seasonal influenza infection as assessed by negativity of RT-PCR for viral RNA in nose and throat swabs at the 5th swab [H48±3] and at the 7th swab [H84±3].
Time frame: 84 hours
5 secondary outcomes
Describe the antiviral efficacy in combination therapy arms (1,2) and in monotherapy arm (3) in the treatment of seasonal influenza infection as assessed by time to sustained negativity of RT-PCR for viral RNA or viral culture in any sample.
Time frame: 168 hours
Assess viral replication dynamics (duration and level of viral replication) in the respiratory tract in the combination and standard-dose cohorts.
Time frame: 168 hours
Assess the frequency, genetic basis, and duration of antiviral resistance to each arm during and after therapy
Time frame: 168 hours
Describe the time to alleviation of illness in the 3 arms defined as the time from the beginning of the study treatment to the time that 7 typical key symptoms of natural influenza had reduced to absent or mi
Time frame: 168 hours
Describe the tolerability of combination and in standard-dose arms as assessed by clinical adverse events that are possibly or probably related to each single agent (Incidence and duration)
Time frame: 168 hours
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2010.
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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.
BRUNO LINA, MD,PhD principal investigator
Hospices Civils de Lyon
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing oseltamivir + zanamivir, oseltamivir+ amantadine and oseltamivir in people with Influenza A Infection, run by Hospices Civils de Lyon 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 8 inclusion and 10 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 30 Sep 2010. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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. 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?
describe the antiviral efficacy in the 3 arms in the treatment of seasonal influenza infection as assessed by negative viral detection in nose swabs at the fifth swab [H48±3] (time frame: 48 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Sep 2010; AzTrials last refreshed its copy on 8 Nov 2026.