Sinusitis
Conditions
Keywords
Respiratory Tract Infection, Bacterial Sinusitis
Brief summary
The purpose of the study is to evaluate the effectiveness and safety of Avelox in a 5 day treatment of adult patients with acute bacterial sinusitis and to measure the amount of time it takes for symptom relief. Avelox is currently not approved for the 5 day treatment of acute bacterial sinusitis, therefore in this study Avelox is considered an investigational drug. In this study Avelox will be compared to placebo.
Interventions
Moxifloxacin - 400 mg once a day for 5 days
DRUGPlacebo
Placebo - 380 mg Microcrystalline Cellulose
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects must meet all the following criteria at the time of enrollment: * Age \>/= 18 years * Clinical diagnosis of acute bacterial sinusitis with signs and symptoms present for = 7 days but \< 28 days as defined by A), radiographic, and B) clinical criteria, as follows: * Radiographic Criteria: The presence of one or more of the following on a radiographic paranasal sinus film (Waters' view): - Evidence of air-fluid levels - Opacification * Clinical Criteria: The presence of two major symptoms, or the presence of at least one major and one minor symptom as defined in the list below: * Major symptoms: - Purulent anterior or posterior nasal discharge - Unilateral facial pain or malar tenderness * Minor symptoms: - Frontal headache - Fever (oral = 38.0°C/100.4°F, tympanic = 38.5°C/101.2°F, axillary = 37.5°C/99.5°F) - Culture material obtained by sinus puncture; the aspirated specimen sent for Gram stain, quantitative culture and susceptibility testing prior to initiation of antimicrobial therapy
Exclusion criteria
Subjects with one or more of the following criteria will not be eligible for this study: * History of chronic sinusitis defined as greater than four weeks of continuous symptoms (subjects with recurrent acute sinusitis will be included) * History of sinus surgery (antral sinus puncture is not considered as a surgery) * Any symptoms that suggest the subject's current illness is allergic rhinitis (e.g. repetitive sneezing, itchy nose or eyes, provocation by an allergen) and not acute bacterial sinusitis * Known bacteremia, meningitis or infection infiltrating the tissues neighboring the sinuses
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Clinical Cure (Modified Intent-to-Treat (MITT)) | At 'Test-of-Cure' (TOC), Day 1-5 after end of treatment | The primary efficacy variable was clinical response (CR) at the TOC visit, and was rated as improvement, complete resolution, failure, or indeterminate. Clinical cure, ie, success, was defined as complete resolution or improvement in the signs and symptoms such that no further therapy (antimicrobial, steroid, or irrigation) was required. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Day When Patients Reached Symptom Improvement as Measured by Patient Reported Data, Using Last Observation Carried Forward (LOCF) Approach | Daily until 'Test-Of-Cure' (Day 1-5 after end of treatment) | The Sino-Nasal Outcome Test (SNOT-16) was used to assess subject-reported time to symptom improvement. Improvement was defined as a decrease of at least 14 units on the test. This difference is the smallest difference that has been identified as beneficial to subjects. |
| Treatment Day When Patients Returned to Normal Activities as Measured by Patient Reported Data, Using LOCF Approach | Daily until 'Test-Of-Cure' (Day 1-5 after end of treatment) | The Activity Impairment Assessment (AIA) questionnaire was used to assess activity impairment at baseline and time to return to normal activities. The AIA was administered prior to first dose, every 24 hours during treatment, and at the TOC visit. Improvement in the AIA total score was defined as a decrease of at least 3 units. |
| Percentage of Subjects With Clinical Improvement During Therapy | Day 3 of treatment | A secondary efficacy variable was clinical response (CR) at the During Therapy visit at day 3 or 4 of treatment. CR was rated as improvement, cure, failure, or indeterminate. Clinical evaluation was based on the presence and severity (mild, moderate, or severe) of several signs and symptoms of acute sinusitis. |
| Percentage of Subjects With Continued Clinical Cure During Long-Term Follow-Up | Day 12 to 26 after end of treatment | A secondary efficacy variable was clinical response (CR) at the Follow-up visit 17-21 days following the start of treatment. CR was rated as continued cure, failure/relapse, or indeterminate. Clinical evaluation was based on the presence and severity (mild, moderate, or severe) of several signs and symptoms of acute sinusitis. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Clinical Cure (Per Protocol Population (PP)) | At 'Test-of-Cure', Day 1-5 after end of treatment | The primary efficacy variable was clinical response (CR) at the TOC visit, and was rated as improvement, complete resolution, failure, or indeterminate. Clinical cure, ie, success, was defined as complete resolution or improvement in the signs and symptoms such that no further therapy (antimicrobial, steroid, or irrigation) was required. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 37 investigative centers in the United States from January 2005 to March 2008.
Pre-assignment details
Modified Intent-to-Treat (MITT): Subjects who received at least 1 dose of study drug with a baseline sinus culture positive for at least 1 of 5 common bacteria that cause sinusitis (73 moxifloxacin \[M\], 45 placebo \[P\]). Per protocol (PP): Subjects with a positive baseline culture (as above) meeting a long list of additional criteria (62 M, 42 P).
Participants by arm
| Arm | Count |
|---|---|
| Moxifloxacin 400 mg Moxifloxacin 400mg once daily for 5 days | 251 |
| Placebo Matching placebo for 5 days | 123 |
| Total | 374 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow up | Lack of Efficacy | 0 | 1 |
| Follow up | Lost to Follow-up | 1 | 1 |
| Treatment | Adverse Event | 3 | 1 |
| Treatment | Lack of Efficacy | 21 | 20 |
| Treatment | Lost to Follow-up | 3 | 1 |
| Treatment | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Placebo | Moxifloxacin 400 mg |
|---|---|---|---|
| Age Continuous | 40.2 years STANDARD_DEVIATION 13.5 | 40.3 years STANDARD_DEVIATION 13 | 40.1 years STANDARD_DEVIATION 13.8 |
| Causative Organisms Isolated from Pretreatment Specimens at Study Entry Haemophilus influenzae | 43 participants | 15 participants | 28 participants |
| Causative Organisms Isolated from Pretreatment Specimens at Study Entry Moraxella catarrhalis | 19 participants | 12 participants | 7 participants |
| Causative Organisms Isolated from Pretreatment Specimens at Study Entry Non causative pathogene | 98 participants | 32 participants | 66 participants |
| Causative Organisms Isolated from Pretreatment Specimens at Study Entry No pathogene growth | 154 participants | 45 participants | 109 participants |
| Causative Organisms Isolated from Pretreatment Specimens at Study Entry Staphylococcus aureus | 16 participants | 5 participants | 11 participants |
| Causative Organisms Isolated from Pretreatment Specimens at Study Entry Streptococcus pneumoniae | 45 participants | 13 participants | 32 participants |
| Causative Organisms Isolated from Pretreatment Specimens at Study Entry Streptococcus pyogenes | 4 participants | 2 participants | 2 participants |
| Duration of infection | 13.0 days STANDARD_DEVIATION 5.1 | 12.7 days STANDARD_DEVIATION 4.7 | 13.2 days STANDARD_DEVIATION 5.4 |
| Location of infection Bilateral | 115 participants | 40 participants | 75 participants |
| Location of infection Left | 119 participants | 37 participants | 82 participants |
| Location of infection Right | 140 participants | 46 participants | 94 participants |
| Severity of infection Mild | 10 participants | 2 participants | 8 participants |
| Severity of infection Moderate | 225 participants | 72 participants | 153 participants |
| Severity of infection Severe | 139 participants | 49 participants | 90 participants |
| Sex: Female, Male Female | 245 Participants | 80 Participants | 165 Participants |
| Sex: Female, Male Male | 129 Participants | 43 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 49 / 251 | 23 / 123 |
| serious Total, serious adverse events | 1 / 251 | 1 / 123 |
Outcome results
Primary
Percentage of Subjects With Clinical Cure (Modified Intent-to-Treat (MITT))
The primary efficacy variable was clinical response (CR) at the TOC visit, and was rated as improvement, complete resolution, failure, or indeterminate. Clinical cure, ie, success, was defined as complete resolution or improvement in the signs and symptoms such that no further therapy (antimicrobial, steroid, or irrigation) was required.
Time frame: At 'Test-of-Cure' (TOC), Day 1-5 after end of treatment
Population: The modified intent-to-treat (MITT) population was the primary analysis population. This population includes all subjects treated with at least one dose of study medication, and who have at least one pre-treatment causative organism.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Moxifloxacin 400 mg | Percentage of Subjects With Clinical Cure (Modified Intent-to-Treat (MITT)) | Failure | 19.2 Percentage of subjects |
| Moxifloxacin 400 mg | Percentage of Subjects With Clinical Cure (Modified Intent-to-Treat (MITT)) | Complete resolution | 12.3 Percentage of subjects |
| Moxifloxacin 400 mg | Percentage of Subjects With Clinical Cure (Modified Intent-to-Treat (MITT)) | Indeterminate | 2.7 Percentage of subjects |
| Moxifloxacin 400 mg | Percentage of Subjects With Clinical Cure (Modified Intent-to-Treat (MITT)) | Improvement | 65.8 Percentage of subjects |
| Moxifloxacin 400 mg | Percentage of Subjects With Clinical Cure (Modified Intent-to-Treat (MITT)) | Success (Clinical Cure) | 78.1 Percentage of subjects |
| Placebo | Percentage of Subjects With Clinical Cure (Modified Intent-to-Treat (MITT)) | Improvement | 55.6 Percentage of subjects |
| Placebo | Percentage of Subjects With Clinical Cure (Modified Intent-to-Treat (MITT)) | Success (Clinical Cure) | 66.7 Percentage of subjects |
| Placebo | Percentage of Subjects With Clinical Cure (Modified Intent-to-Treat (MITT)) | Failure | 33.3 Percentage of subjects |
| Placebo | Percentage of Subjects With Clinical Cure (Modified Intent-to-Treat (MITT)) | Indeterminate | 0 Percentage of subjects |
| Placebo | Percentage of Subjects With Clinical Cure (Modified Intent-to-Treat (MITT)) | Complete resolution | 11.1 Percentage of subjects |
Comparison: Null hypothesis is that the success rate for moxifloxacin = the success rate for placebop-value: 0.189Cochran-Mantel-Haenszel
Secondary
Percentage of Subjects With Clinical Improvement During Therapy
A secondary efficacy variable was clinical response (CR) at the During Therapy visit at day 3 or 4 of treatment. CR was rated as improvement, cure, failure, or indeterminate. Clinical evaluation was based on the presence and severity (mild, moderate, or severe) of several signs and symptoms of acute sinusitis.
Time frame: Day 3 of treatment
Population: The MITT population was the primary analysis population. This population includes all subjects treated with at least one dose of study medication, and who have at least one pre-treatment causative organism. Missing responses at during therapy visit in most cases was due to early clinical failure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Moxifloxacin 400 mg | Percentage of Subjects With Clinical Improvement During Therapy | Improvement | 84.9 Percentage of subjects |
| Moxifloxacin 400 mg | Percentage of Subjects With Clinical Improvement During Therapy | Indeterminate | 4.1 Percentage of subjects |
| Moxifloxacin 400 mg | Percentage of Subjects With Clinical Improvement During Therapy | Missing | 11.0 Percentage of subjects |
| Placebo | Percentage of Subjects With Clinical Improvement During Therapy | Improvement | 73.3 Percentage of subjects |
| Placebo | Percentage of Subjects With Clinical Improvement During Therapy | Indeterminate | 4.4 Percentage of subjects |
| Placebo | Percentage of Subjects With Clinical Improvement During Therapy | Missing | 22.2 Percentage of subjects |
Secondary
Percentage of Subjects With Continued Clinical Cure During Long-Term Follow-Up
A secondary efficacy variable was clinical response (CR) at the Follow-up visit 17-21 days following the start of treatment. CR was rated as continued cure, failure/relapse, or indeterminate. Clinical evaluation was based on the presence and severity (mild, moderate, or severe) of several signs and symptoms of acute sinusitis.
Time frame: Day 12 to 26 after end of treatment
Population: The MITT population was the primary analysis population. This population includes all subjects treated with at least one dose of study medication, and who have at least one pre-treatment causative organism.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Moxifloxacin 400 mg | Percentage of Subjects With Continued Clinical Cure During Long-Term Follow-Up | Combined Clinical Cure | 73.9 Percentage of subjects |
| Moxifloxacin 400 mg | Percentage of Subjects With Continued Clinical Cure During Long-Term Follow-Up | Clinical Failure / Relapse | 21.9 Percentage of subjects |
| Moxifloxacin 400 mg | Percentage of Subjects With Continued Clinical Cure During Long-Term Follow-Up | Missing | 4.1 Percentage of subjects |
| Placebo | Percentage of Subjects With Continued Clinical Cure During Long-Term Follow-Up | Missing | 2.2 Percentage of subjects |
| Placebo | Percentage of Subjects With Continued Clinical Cure During Long-Term Follow-Up | Combined Clinical Cure | 57.7 Percentage of subjects |
| Placebo | Percentage of Subjects With Continued Clinical Cure During Long-Term Follow-Up | Clinical Failure / Relapse | 40.0 Percentage of subjects |
Secondary
Treatment Day When Patients Reached Symptom Improvement as Measured by Patient Reported Data, Using Last Observation Carried Forward (LOCF) Approach
The Sino-Nasal Outcome Test (SNOT-16) was used to assess subject-reported time to symptom improvement. Improvement was defined as a decrease of at least 14 units on the test. This difference is the smallest difference that has been identified as beneficial to subjects.
Time frame: Daily until 'Test-Of-Cure' (Day 1-5 after end of treatment)
Population: The MITT population was the primary analysis population. This population includes all subjects treated with at least one dose of study medication, and who have at least one pre-treatment causative organism.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Moxifloxacin 400 mg | Treatment Day When Patients Reached Symptom Improvement as Measured by Patient Reported Data, Using Last Observation Carried Forward (LOCF) Approach | Day 3 | 26 participants |
| Moxifloxacin 400 mg | Treatment Day When Patients Reached Symptom Improvement as Measured by Patient Reported Data, Using Last Observation Carried Forward (LOCF) Approach | Day 5 | 39 participants |
| Moxifloxacin 400 mg | Treatment Day When Patients Reached Symptom Improvement as Measured by Patient Reported Data, Using Last Observation Carried Forward (LOCF) Approach | Day 4 | 31 participants |
| Moxifloxacin 400 mg | Treatment Day When Patients Reached Symptom Improvement as Measured by Patient Reported Data, Using Last Observation Carried Forward (LOCF) Approach | Test-Of-Cure | 43 participants |
| Moxifloxacin 400 mg | Treatment Day When Patients Reached Symptom Improvement as Measured by Patient Reported Data, Using Last Observation Carried Forward (LOCF) Approach | Day 2 | 14 participants |
| Placebo | Treatment Day When Patients Reached Symptom Improvement as Measured by Patient Reported Data, Using Last Observation Carried Forward (LOCF) Approach | Test-Of-Cure | 19 participants |
| Placebo | Treatment Day When Patients Reached Symptom Improvement as Measured by Patient Reported Data, Using Last Observation Carried Forward (LOCF) Approach | Day 2 | 7 participants |
| Placebo | Treatment Day When Patients Reached Symptom Improvement as Measured by Patient Reported Data, Using Last Observation Carried Forward (LOCF) Approach | Day 3 | 10 participants |
| Placebo | Treatment Day When Patients Reached Symptom Improvement as Measured by Patient Reported Data, Using Last Observation Carried Forward (LOCF) Approach | Day 4 | 13 participants |
| Placebo | Treatment Day When Patients Reached Symptom Improvement as Measured by Patient Reported Data, Using Last Observation Carried Forward (LOCF) Approach | Day 5 | 16 participants |
Secondary
Treatment Day When Patients Returned to Normal Activities as Measured by Patient Reported Data, Using LOCF Approach
The Activity Impairment Assessment (AIA) questionnaire was used to assess activity impairment at baseline and time to return to normal activities. The AIA was administered prior to first dose, every 24 hours during treatment, and at the TOC visit. Improvement in the AIA total score was defined as a decrease of at least 3 units.
Time frame: Daily until 'Test-Of-Cure' (Day 1-5 after end of treatment)
Population: The MITT population was the primary analysis population. This population includes all subjects treated with at least one dose of study medication, and who have at least one pre-treatment causative organism.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Moxifloxacin 400 mg | Treatment Day When Patients Returned to Normal Activities as Measured by Patient Reported Data, Using LOCF Approach | Test-Of-Cure | 42 participants |
| Moxifloxacin 400 mg | Treatment Day When Patients Returned to Normal Activities as Measured by Patient Reported Data, Using LOCF Approach | Day 4 | 35 participants |
| Moxifloxacin 400 mg | Treatment Day When Patients Returned to Normal Activities as Measured by Patient Reported Data, Using LOCF Approach | Day 2 | 22 participants |
| Moxifloxacin 400 mg | Treatment Day When Patients Returned to Normal Activities as Measured by Patient Reported Data, Using LOCF Approach | Day 5 | 37 participants |
| Moxifloxacin 400 mg | Treatment Day When Patients Returned to Normal Activities as Measured by Patient Reported Data, Using LOCF Approach | Day 3 | 31 participants |
| Placebo | Treatment Day When Patients Returned to Normal Activities as Measured by Patient Reported Data, Using LOCF Approach | Day 5 | 19 participants |
| Placebo | Treatment Day When Patients Returned to Normal Activities as Measured by Patient Reported Data, Using LOCF Approach | Day 3 | 17 participants |
| Placebo | Treatment Day When Patients Returned to Normal Activities as Measured by Patient Reported Data, Using LOCF Approach | Day 4 | 17 participants |
| Placebo | Treatment Day When Patients Returned to Normal Activities as Measured by Patient Reported Data, Using LOCF Approach | Test-Of-Cure | 22 participants |
| Placebo | Treatment Day When Patients Returned to Normal Activities as Measured by Patient Reported Data, Using LOCF Approach | Day 2 | 15 participants |
Other Pre-specified
Percentage of Subjects With Clinical Cure (Per Protocol Population (PP))
The primary efficacy variable was clinical response (CR) at the TOC visit, and was rated as improvement, complete resolution, failure, or indeterminate. Clinical cure, ie, success, was defined as complete resolution or improvement in the signs and symptoms such that no further therapy (antimicrobial, steroid, or irrigation) was required.
Time frame: At 'Test-of-Cure', Day 1-5 after end of treatment
Population: This analysis population was per protocol population, which included all subjects with at least one pre-treatment causative organism, and who had no major deviations from the protocol procedures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Moxifloxacin 400 mg | Percentage of Subjects With Clinical Cure (Per Protocol Population (PP)) | Improvement | 71.0 Percentage of subjects |
| Moxifloxacin 400 mg | Percentage of Subjects With Clinical Cure (Per Protocol Population (PP)) | Failure | 17.7 Percentage of subjects |
| Moxifloxacin 400 mg | Percentage of Subjects With Clinical Cure (Per Protocol Population (PP)) | Indeterminate | 0 Percentage of subjects |
| Moxifloxacin 400 mg | Percentage of Subjects With Clinical Cure (Per Protocol Population (PP)) | Complete resolution | 11.3 Percentage of subjects |
| Moxifloxacin 400 mg | Percentage of Subjects With Clinical Cure (Per Protocol Population (PP)) | Success | 82.3 Percentage of subjects |
| Placebo | Percentage of Subjects With Clinical Cure (Per Protocol Population (PP)) | Indeterminate | 0 Percentage of subjects |
| Placebo | Percentage of Subjects With Clinical Cure (Per Protocol Population (PP)) | Success | 66.7 Percentage of subjects |
| Placebo | Percentage of Subjects With Clinical Cure (Per Protocol Population (PP)) | Complete resolution | 9.5 Percentage of subjects |
| Placebo | Percentage of Subjects With Clinical Cure (Per Protocol Population (PP)) | Failure | 33.3 Percentage of subjects |
| Placebo | Percentage of Subjects With Clinical Cure (Per Protocol Population (PP)) | Improvement | 57.1 Percentage of subjects |
Comparison: Null hypothesis is that the success rate for moxifloxacin = the success rate for placebop-value: 0.075Cochran-Mantel-Haenszel