Sinusitis, Bacterial Infections
Conditions
Keywords
Treatment of acute bacterial rhinosinusitis
Brief summary
This is a clinical study organized to collect clinical data to better define the activity of some antimicrobials already marketed in Italy and in the rest of the world for the treatment of acute bacterial rhinosinusitis
Interventions
Patients will be administered daily a single moxifloxacin 400 mg tablet for 7 days
Patient will be administered daily Amoxicilline/Clavulanate 1000 mg tablets every 8 hours for 10 days
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>= 18 years * Clinical diagnosis of acute rhinosinusitis with signs and symptoms present for \>/= 5-7 days but \< 28 days * Clinical diagnosis will be confirmed by nasal endoscopic examination
Exclusion criteria
* History of chronic sinusitis defined as greater than four weeks of continuous symptoms (subject with history of sinus surgery may be included; subjects with recurrent acute sinusitis may be included) * 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 * Known immunodeficiency diseases including, but not limited to: neutropenia (neutrophil count \< 1000/mm3), human immunodeficiency virus (HIV) infection (Cluster of differentiation 4 (CD4)+ T-cell count of \< 200/mm3). Note: HIV testing is not required * Received systemic antibacterial therapy likely to be effective in the treatment of acute bacterial sinusitis for more than 24 hours within 5/6 days of enrollment * Requirement for concomitant systemic antibacterial therapy with agents other than those specified in this protocol * Currently receiving topical nasal corticosteroids, unless they have been on a stable dose for \> 4 weeks prior to enrollment * Requirement for concomitant therapy with systemic corticosteroids * Pregnant or breast feeding * Of childbearing potential in whom pregnancy cannot be excluded by a negative pregnancy test and who are not using reliable barrier method of contraception * Received an investigational drug in the past 30 days * Previously enrolled in this study * Unable to take oral medication * History of allergy to quinolone antibiotics or related compounds and beta-lactams * History of tendinopathy associated with quinolones * Known to have congenital or sporadic syndromes of QT interval corrected for rate (QTc) prolongation or receiving concomitant medication reported to increase the QTc interval (e.g. amiodarone, sotalol, disopyramide, quinidine, procainamide, terfenadine) * Uncorrected hypokalemia * End stage liver cirrhosis (class Child-Pugh C) * Severe renal impairment requiring dialysis * Diagnosis of rapidly fatal illness with a life expectancy of less than 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Response (Per-protocol Population) | At 'Test-of-Cure', Day 1-3 after treatment | Number of patients in the population who met criteria pre-specified in the protocol whose clinical response 1-3 days after treatment was assessed by the investigator as clinical cure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Response (Intent-to-treat Population) | At 'Test-of-Cure', Day 1-3 after treatment | Number of patients in the population who received at least one dose of study medication whose clinical response 1-3 days after treatment was assessed by the investigator as clinical cure |
| Number of Participants With Response (Per-protocol Population) | End of Follow-up, Day 24-30 after treatment | Number of patients in the population who met criteria pre-specified in the protocol whose clinical response 24-30 days after treatment was assessed by the investigator as continued clinical cure |
| Number of Participants With Response (Microbiologically Valid Patients) | At 'Test-of-Cure', Day 1-3 after treatment | Bacteriological Efficacy Rate at the 'Test-of-Cure' visit, measured in patients defined as 'microbiologically valid'. A bacteriological success is an eradication without super- or reinfection or presumed eradication. |
Countries
Italy
Participant flow
Recruitment details
Enrollment started on 13 Feb 2006 and the last study visit occurred on 20 Jan 2008. The study was conducted at 34 active otorhinolaryngology centers in Italy.
Pre-assignment details
Number of patients screened: 293 Number of patients having at least one observation under study medication: 287 (intention-to-treat population = ITT population) Number of patients adhered to major predefined aspects of the study protocol: 251 (per-protocol population = PP population). Primary population for efficacy was PP.
Participants by arm
| Arm | Count |
|---|---|
| Moxifloxacin (Avelox, BAY12-8039) Moxifloxacin (Avelox, BAY12-8039) 400 mg tablets once daily (OD) for 7 days and amoxicillin/clavulanate 1000 mg matching placebo tablets three times daily (TID) for 10 days | 145 |
| Amoxicillin/Clavulanate Amoxicillin/clavulanate 1000 mg matching tablets three times daily (TID) for 10 days and moxifloxacin 400 mg matching placebo tablets once daily (OD) for 7 days | 142 |
| Total | 287 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-up | Lost to Follow-up | 1 | 0 |
| Treatment | Adverse Event | 8 | 4 |
| Treatment | Lost to Follow-up | 5 | 3 |
| Treatment | Other | 0 | 1 |
| Treatment | Withdrawal by Subject | 11 | 12 |
Baseline characteristics
| Characteristic | Moxifloxacin (Avelox, BAY12-8039) | Amoxicillin/Clavulanate | Total |
|---|---|---|---|
| Age, Continuous | 41.7 years STANDARD_DEVIATION 13.2 | 39.7 years STANDARD_DEVIATION 13.6 | 40.7 years STANDARD_DEVIATION 13.4 |
| Age, Customized >18 and <65 years | 133 participants | 132 participants | 265 participants |
| Age, Customized <=18 years | 0 participants | 0 participants | 0 participants |
| Age, Customized >=65 years | 12 participants | 10 participants | 22 participants |
| Sex: Female, Male Female | 63 Participants | 75 Participants | 138 Participants |
| Sex: Female, Male Male | 82 Participants | 67 Participants | 149 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 145 | 0 / 142 |
| serious Total, serious adverse events | 1 / 145 | 1 / 142 |
Outcome results
Primary
Number of Participants With Response (Per-protocol Population)
Number of patients in the population who met criteria pre-specified in the protocol whose clinical response 1-3 days after treatment was assessed by the investigator as clinical cure
Time frame: At 'Test-of-Cure', Day 1-3 after treatment
Population: Per Protocol population: subjects to meet all of the following (1) Clinical evaluation was performed at TOC visit (2) No other systemic antibacterial agent was administered with study drug up to TOC visit (3) Adequate treatment compliance (≥ 80% of study drug taken) (4) Random code not broken (5) No protocol violation affecting treatment efficacy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Moxifloxacin (Avelox, BAY12-8039) | Number of Participants With Response (Per-protocol Population) | 119 participants |
| Amoxicillin/Clavulanate | Number of Participants With Response (Per-protocol Population) | 125 participants |
Comparison: Calculated were 95% confidence intervals for the difference in success rates between treatment groups (moxifloxacin minus comparator). Method as described in Koch et al. ('Categorical Data Analysis' in Statistical methodology in the pharmaceutical sciences / edited by D. A. Berry, p. 415 ff., Marcel Dekker, 1990)95% CI: [-1.9, 6.2]
Secondary
Number of Participants With Response (Intent-to-treat Population)
Number of patients in the population who received at least one dose of study medication whose clinical response 1-3 days after treatment was assessed by the investigator as clinical cure
Time frame: At 'Test-of-Cure', Day 1-3 after treatment
Population: ITT population: participants having at least one observation under study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Moxifloxacin (Avelox, BAY12-8039) | Number of Participants With Response (Intent-to-treat Population) | 128 participants |
| Amoxicillin/Clavulanate | Number of Participants With Response (Intent-to-treat Population) | 127 participants |
Comparison: Calculated were 95% confidence intervals for the difference in success rates between treatment groups (moxifloxacin minus comparator). Method as described in Koch et al. ('Categorical Data Analysis' in Statistical methodology in the pharmaceutical sciences / edited by D. A. Berry, p. 415 ff., Marcel Dekker, 1990)95% CI: [-7.9, 6.8]
Secondary
Number of Participants With Response (Microbiologically Valid Patients)
Bacteriological Efficacy Rate at the 'Test-of-Cure' visit, measured in patients defined as 'microbiologically valid'. A bacteriological success is an eradication without super- or reinfection or presumed eradication.
Time frame: At 'Test-of-Cure', Day 1-3 after treatment
Population: Patients valid per protocol with a causative organism cultured.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Moxifloxacin (Avelox, BAY12-8039) | Number of Participants With Response (Microbiologically Valid Patients) | Bacteriological success | 21 Participants |
| Moxifloxacin (Avelox, BAY12-8039) | Number of Participants With Response (Microbiologically Valid Patients) | Failure | 0 Participants |
| Amoxicillin/Clavulanate | Number of Participants With Response (Microbiologically Valid Patients) | Bacteriological success | 25 Participants |
| Amoxicillin/Clavulanate | Number of Participants With Response (Microbiologically Valid Patients) | Failure | 1 Participants |
Secondary
Number of Participants With Response (Microbiologically Valid Patients)
Bacteriological Efficacy Rate at the End of Follow-up period, measured in patients defined as 'microbiologically valid'. A bacteriological success is an eradication without super- or reinfection or presumed eradication.
Time frame: End of Follow-up, Day 24-30 after treatment
Population: Patients valid per protocol with a causative organism cultured.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Moxifloxacin (Avelox, BAY12-8039) | Number of Participants With Response (Microbiologically Valid Patients) | Bacteriological success | 19 Participants |
| Moxifloxacin (Avelox, BAY12-8039) | Number of Participants With Response (Microbiologically Valid Patients) | Failure | 0 Participants |
| Moxifloxacin (Avelox, BAY12-8039) | Number of Participants With Response (Microbiologically Valid Patients) | Missing / Indeterminate | 2 Participants |
| Amoxicillin/Clavulanate | Number of Participants With Response (Microbiologically Valid Patients) | Bacteriological success | 23 Participants |
| Amoxicillin/Clavulanate | Number of Participants With Response (Microbiologically Valid Patients) | Failure | 0 Participants |
| Amoxicillin/Clavulanate | Number of Participants With Response (Microbiologically Valid Patients) | Missing / Indeterminate | 3 Participants |
Secondary
Number of Participants With Response (Per-protocol Population)
Number of patients in the population who met criteria pre-specified in the protocol whose clinical response 24-30 days after treatment was assessed by the investigator as continued clinical cure
Time frame: End of Follow-up, Day 24-30 after treatment
Population: PP population at end FU: (1) Clinical evaluation was performed at the TOC visit (2) No other systemic antibacterial agent was administered with study drug up to the TOC visit (3) Adequate treatment compliance (≥80% of study drug taken) (4) Random code not broken (5) No protocol violation affecting treatment efficacy (6) FU assessment available
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Moxifloxacin (Avelox, BAY12-8039) | Number of Participants With Response (Per-protocol Population) | 108 participants |
| Amoxicillin/Clavulanate | Number of Participants With Response (Per-protocol Population) | 117 participants |
Comparison: Calculated were 95% confidence intervals for the difference in success rates between treatment groups (moxifloxacin minus comparator). Method as described in Koch et al. ('Categorical Data Analysis' in Statistical methodology in the pharmaceutical sciences / edited by D. A. Berry, p. 415 ff., Marcel Dekker, 1990)95% CI: [-3.8, 7.1]