The primary objective is to compare the efficacy of moxifloxacin 400 mg PO OD for five days with the respective efficacy of amoxicillin clavulanic acid 875/125 mg PO BID for seven days in the treatment of subjects with AECB. The primary efficacy…
ID
Source
Brief title
Condition
- Bacterial infectious disorders
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective is to compare the efficacy of moxifloxacin 400 mg PO OD
for five days with the respective efficacy of amoxicillin clavulanic acid
875/125 mg PO BID for seven days in the treatment of subjects with AECB. The
primary efficacy endpoint will be clinical failure rates at 8 weeks post-
therapy visit in outpatients with AECB.
Clinical failure is defined as the requirement for additional (including
increased dose or duration of treatment) systemic antibiotics and/or systemic
corticosteroids and/or hospitalization with antibiotic and/or systemic
corticosteroid administration within 8 weeks post therapy.
Secondary outcome
• Clinical efficacy rates at the During Therapy, End of Therapy (EOT), and at 4
weeks Post therapy visits
• Bacteriological eradication rates at the During Therapy, EOT, 4 weeks and 8
weeks Post therapy visits
• Clinical efficacy rates (for subjects with positive sputum culture at
enrollment) at the During Therapy, EOT, and 4 weeks Post therapy and 8 weeks
Post therapy visits
• Weekly mean symptom scores measured by the Acute Exacerbation of Chronic
Bronchitis Symptom Scale (AECB SS)
• Rates and speed of symptom relief measured by the AECB SS
• Need for any change in dosage or additional respiratory medication such as
bronchodilators and inhaled steroids, excluding short acting bronchodilators
• Improvement in symptom burden measured by the AECB SS
• Improvement in health related QoL measured by The St. George*s Hospital
Respiratory Questionnaire (SGRQ)
• Lung function test will be compared between treatment groups at each
assessment visit
• Healthcare resource utilization/consumption related to chronic bronchitis
management including rescue medications, concomitant medications, therapeutic
adjuncts, diagnosis procedures, other medical care/medical staff requirements,
hospitalizations, and work productivity and activity impairment
• Safety and tolerability of moxifloxacin versus amoxicillin clavulanic acid,
with particular attention to rates of diarrhea
Background summary
Chronic bronchitis is defined as a clinical diagnosis in patients presenting
with persistent cough and excessive secretion of mucus resulting in sputum
production on most days for at least three consecutive months in two
consecutive years. Due to its chronic course, and periodic attacks of acute
exacerbations, therapeutic management of chronic bronchitis exerts a
substantial economic burden on society. The etiology of acute exacerbations of
chronic bronchitis (AECB) is multifactorial in nature, with bacterial agents
accounting for approximately 50% of AECB episodes, investigational studies have
shown that the number of patients with pathogenic bacteria in the respiratory
secretions and airway bacterial load, increased during exacerbations. These
studies, involving sputum analysis, bronchoscopic sampling, molecular
epidemiology of bacterial strains, and immunology have linked the presence of
bacterial infection. Patients with AECB are usually treated with empiric
antibiotic therapy because the causative pathogen is generally not identified
in clinical practice. The benefits of antibiotic therapy for AECB have been
demonstrated in numerous clinical studies, especially in subjects with more
severe airflow obstruction and at least two of the three following symptoms:
increased dyspnea, increased sputum volume, and/or increased sputum purulence.
Moxifloxacin, an 8 methoxyfluoroquinolone, has activity against all key
respiratory tract pathogens There is growing evidence that despite the apparent
successful management of AECB in patients with COPD, these episodes result in
progressive lung damage with deteriorating lung function over time. In
addition, both the acute exacerbations and the long-term sequelae of AECB
result in significant morbidity, mortality and deterioration in quality of life.
The recent multinational, randomized MOSAIC study compared moxifloxacin with
the bucket of comparators (amoxicillin, clarithromycin and cefuroxime axetil)
in patients with Anthonisen type 1 AECB. Although moxifloxacin and the
comparator regimens were equivalent in terms of clinical success rates (cure
plus improvement) at 7 to 10 days after therapy, moxifloxacin showed
superiority over the comparator group in clinical cure rates in patients who
were not treated with systemic corticosteroids or were on stable systemic
corticosteroid treatment (p=0.03). In addition, superiority of moxifloxacin was
seen in bacteriological eradication and long term outcomes. Moreover, subjects
65 years or older, or with four or more exacerbations per year in the
moxifloxacin group appeared to have a prolonged time to treatment
failure/relapse and a lower number of acute exacerbations within six to eight
weeks following the treatment and onward, than in the comparator group. This
early difference between the two treatment groups suggested that the main, long
term difference was primarily accrued in the first six to eight weeks post
antimicrobial treatment, perhaps due to the persistence of bacterial infection.
Thus, this period requires further investigations to assess the reasons for
treatment failures and the type of exacerbations occurring early after
antibiotic treatment.
Study objective
The primary objective is to compare the efficacy of moxifloxacin 400 mg PO OD
for five days with the respective efficacy of amoxicillin clavulanic acid
875/125 mg PO BID for seven days in the treatment of subjects with AECB. The
primary efficacy endpoint will be clinical failure rates at 8 weeks post-
therapy visit in outpatients with AECB.
Clinical failure is defined as the requirement for additional (including
increased dose or duration of treatment) systemic antibiotics and/or systemic
corticosteroids and/or hospitalization with antibiotic and/or systemic
corticosteroid administration within 8 weeks post therapy.
Secondary objectives:
• Clinical efficacy rates at the During Therapy, End of Therapy (EOT), and at 4
weeks Post therapy visits
• Bacteriological eradication rates at the During Therapy, EOT, 4 weeks and 8
weeks Post therapy visits
• Clinical efficacy rates (for subjects with positive sputum culture at
enrollment) at the During Therapy, EOT, and 4 weeks Post therapy and 8 weeks
Post therapy visits
• Weekly mean symptom scores measured by the Acute Exacerbation of Chronic
Bronchitis Symptom Scale (AECB SS)
• Rates and speed of symptom relief measured by the AECB SS
• Need for any change in dosage or additional respiratory medication such as
bronchodilators and inhaled steroids, excluding short acting bronchodilators
• Improvement in symptom burden measured by the AECB SS
• Improvement in health related QoL measured by The St. George*s Hospital
Respiratory Questionnaire (SGRQ)
• Lung function test will be compared between treatment groups at each
assessment visit
• Healthcare resource utilization/consumption related to chronic bronchitis
management including rescue medications, concomitant medications, therapeutic
adjuncts, diagnosis procedures, other medical care/medical staff requirements,
hospitalizations, and work productivity and activity impairment
• Safety and tolerability of moxifloxacin versus amoxicillin clavulanic acid,
with particular attention to rates of diarrhea
Study design
This is a multicenter, multinational, multiregional, prospective, randomized,
double-blind, double dummy, Phase IV clinical study in outpatients with acute
exacerbation of chronic bronchitis, which will determine the clinical non
inferiority at 8 weeks post therapy, of valid per protocol moxifloxacin treated
subjects versus valid per protocol amoxicillin clavulanic acid treated
subjects.
Intervention
Active Treatment Group 1: Moxifloxacin 400 mg PO OD
for 5 days
Active Treatment Group 2: Amoxicillin clavulanic acid 875/125 mg PO BID
for 7 days
Study burden and risks
The number of visits to be completed by patients is, after randomization 4.
In case a premature stop of the study, by whatever reasons as therapy failure,
refusing to proceed etc. one *premature visit* for termination has to be
performed.
During the first 13 days, so during the active treatment, patient should fill
out a diary at home. Afterwards this will be repeated during the remaining
visits in hospital. Then also two questionares will be completed, the AECB-SS
and the SGRO.
During all visits patients will be asked to assess spirometry, i.e. blowing
FEV1.
If the patient is able to produce sputum, this will be sampled during every
visit.
Taken together, the study hardly costs any physical or psychological burden.
The number of visits (max. 5) and filling out the questionnaires might cause
some effort.
Energieweg 1
3641 RT Mijdrecht
NL
Energieweg 1
3641 RT Mijdrecht
NL
Listed location countries
Age
Inclusion criteria
Study subjects must meet all of the following inclusion criteria:
1. Outpatients
2. Male or female subjects, >=60 years old
3. Subject who can be managed with oral antimicrobials
4. FEV1<=50% predicted at enrollment in addition to a historical record of FEV1 of <=60% within the past 12 months obtained during a stable infection-free period. A historical record of FEV1 is not required if the enrollment FEV1 is less than or equal to 50%.
5. Documented history of 2 or more AECB episodes, within 12 months of study enrollment, requiring a course of systemic antibiotics and/or systemic corticosteroids
6. All symptoms/signs must be present and confirmed by the Investigator:
• Increase in dyspnea
• Purulent sputum
• Increase in sputum volume
7. Subject must provide a purulent sputum sample by deep expectoration prior to randomization for Gram stain, culture and sensitivity testing. The sputum will be assessed macroscopically by the investigator and graded according to the provided color chart.
8. Current or past cigarette smoker with >=20 pack year smoking history (Pack years are calculated by dividing the number of cigarettes smoked per day by 20 (number of cigarettes/pack) and multiplying by the number of years a person has smoked)
9. Subjects must have an infection free interval of at least 30 days prior to enrollment
10. Subjects must be willing and able to complete the questionnaires and subject booklet without assistance
11. Subjects with medical conditions and social status at the time of enrollment compatible with study protocol procedures
12. Willing and able to provide written informed consent
Exclusion criteria
Subjects who meet at least one of the following exclusion criteria must be excluded from study participation:
1. Known hypersensitivity to quinolones, ß lactams, or to any of the excipients of the study drugs
2. Known to have congenital or acquired QT prolongation
3. Known to have clinically relevant bradycardia
4. Known to have clinically relevant heart failure with reduced left ventricular ejection fraction
5. Known to have previous history of symptomatic arrhythmias
6. Taking QT prolonging drugs, for example class IA or III antiarrhythmic agents (e.g., quinidine, procainamide, amiodarone, sotalol), neuroleptics (e.g., phenothiazines, pimozide, sertindole, haloperidol, sultopride), tricyclic antidepressants, certain antihistaminics (e.g., terfenadine, astemizole, mizolastine), or other QT prolonging drugs (e.g., cisapride, vincamine iv, bepridil, and diphemanil)
7. Known electrolyte disturbances that are not controlled, particularly uncorrected hypokalemia
8. Known history of hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose galactose malabsorption
9. Requiring hemodialysis
10. History of a tendon disease/disorder
11. Known history of liver dysfunction, including known elevated transaminases (ALT and/or AST >3 times the upper limit of normal)
12. Known severe renal impairment with glomerular filtration rate of <30mL/min
13. Known neutropenia (neutrophil count <1000/mm³) caused by immunosuppressive therapy or malignancy
14. Known to have AIDS (CD4 count of <200/mm³), or be HIV positive and receiving Highly Active Anti Retroviral Therapy (HAART) (HIV testing is not mandatory)
15. Known bronchial carcinoma, active pulmonary tuberculosis, known diffuse bronchiectasis, cystic fibrosis, chronic asthma (>15% reversibility), or pneumonia (a chest X ray is not mandatory)
16. Known history of chronic colonization of pathogenic organisms resistant to moxifloxacin and/or amoxicillin clavulanic acid (e.g., Pseudomonas aeruginosa, MRSA)
17. Receiving long term (>4 consecutive weeks) systemic corticosteroid treatment (>10 mg/day of prednisolone or equivalent) (see Section 4.5.7 Prior and Concomitant Medication)
18. Received short course of systemic corticosteroid treatment within 30 days prior to enrollment
19. Requiring intravenous antibiotic therapy for treatment of the current exacerbation
20. Unable to take oral medication
21. Life expectancy of less than 6 months
22. Receiving systemic antibacterial therapy within 30 days prior to study enrollment
23. Requiring concomitant systemic antibacterial agents
24. Use of any investigational drug or device within 30 days of screening, or previously enrolled in this study
25. Requiring home ventilatory support (subjects requiring home/portable oxygen therapy or CPAP for sleep apnea are not excluded) and/or those who have a tracheotomy in situ
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-006096-37-NL |
| CCMO | NL21808.003.08 |
| Other | Studie wordt geplaatst op www.clinicaltrials.gov, zodra registratienummer beschikbaar is sturen wij dat na. |