Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Double-blind, Randomized, Placebo-controlled Study to Investigate Chronic Intermittent-pulse-therapy of Moxifloxacin as a Prevention of Acute in Exacerbation Out-patients With Chronic Bronchitis.
Brief Summary: Moxifloxacin, is being tested at approximately 60 study centres in 15 countries to determine if this drug, when taken periodically in addition to the patients normal treatment, is effective at reducing the number of flare-ups of chronic bronchitis he has. Approximately 1132 subjects will participate, and it is expected that the study will run for 2 years in order to reach that goal. The patients individual involvement in the study will be 17 months. Moxifloxacin will be compared to a placebo drug (no active ingredients). The study medication (moxifloxacin or placebo) will be taken in addition to the patients normal medication for chronic bronchitis. In addition to the first clinic visit, called a screening visit, the patient will be required to come back to the clinic for ten more study visits, every 8 weeks. At the first visit the study co-ordinator will provide him with the dates for all the visits. Over a period of 48 weeks the patient will return to the clinic on 6 occasions where he will receive the study medication which he will take for five days, in addition to his normal treatment for chronic bronchitis. After this time the patient will enter a follow up period for 24 weeks, where he will come to the clinic for assessments and continue to take his normal medication but not receive the study drug. A complete medical history will be taken at the first visit, including the patients past and current smoking habit. A breath test will be performed to assess how well his lungs are functioning. In addition, he will also be asked to provide a sputum sample for a microbiological examination to identify any bacteria present in the sample. The patient must be able to provide a sputum sample at the screening visit. If the patient meets all the inclusion / exclusion criteria for the study, he will be allocated randomly to one of the following treatment groups at the second visit.- Treatment group 1: Receives moxifloxacin orally once daily for five days.- Treatment group 2: Receives a matching placebo once daily for five days.In between each visit (four weeks after your clinic visit), the study site co-ordinator will contact the patient to check on his well being. If the patient or the doctor decides to stop the patients participation in the trial for any reason, the patient will be required to return to the clinic for a physical examination, take a breath test, provide a sputum sample (if possible) and have a blood sample taken.


Options:
A: Inclusion Criteria:

* Acute exacerbation of COPD type I or II according to GOLD
* Ability to perform lung function tests
* Ability to take oral medication

Exclusion Criteria:

* Pregnant or lactating women, or women of childbearing age not using an acceptable method of contraception.
* Pretreatment ( \> 24 hours) with an antibiotic for the present exacerbation.
* Pretreatment with corticosteroids (\>30 mg for more than 4 days) for the present exacerbation.
* Progression or new radiographic abnormalities on the chest X-ray.
* Severe exacerbation that required mechanical ventilation.
* History of bronchiectasis
* Recent or unresolved lung malignancy.
* Other disease likely to require antibiotic therapy.
* Significant gastrointestinal or other conditions that may affect study drug absorption.
* Class III or IV congestive heart failure or stroke.
* Immunodeficiency disorders such as AIDS, humoral immune defect, ciliary dysfunction etc. and the use of immunosuppressive drugs (\>30 mg prednisolone maintenance dose or equivalent for more than 4 weeks).
* Cystic fibrosis
* Tuberculosis.
* Impaired renal function (creatinine clearance \< 20 ml/min).
B: Inclusion Criteria:

* Acute exacerbations (at least one criterion present: increase of dyspnoea, increase of sputum production and/or increase of purulence) of
* patients older than 40 years old,
* smokers or ex-smokers of more than 10 pack-years,
* with COPD and FEV1 greater than 50%, diagnosed by spirometry and a predicted ratio FEV1/FVC\<0.7%.

Exclusion Criteria:

* Severe COPD (FEV1\<50%)
* Pneumonia
* Active neoplasm
* Tracheotomy
* Criteria for hospitalisation
* Patients previously being on antibiotics
* Immunodepressed patients
* History of hypersensitivity to beta-lactams or intolerance to clavulanate
* Enrollment in other clinical trials
* Patients who refuse to take part in this study
* Patients who have not had a spirometry test for the past two years
C: Inclusion Criteria:

* Adults, either sex, older or equal than 40 years of age
* For female patients, the following conditions are to be met:

  * has been postmenopausal for at least 1 year, or
  * is surgically incapable of bearing children, or
  * is of childbearing potential, and the following conditions are met:

    * has a negative pregnancy test (urine- or serum-based) immediately before study entry (i.e., before the start of treatment or any other study procedure that could potentially harm the fetus), and one or more of following criteria
    * must agree to abstinence or use an accepted method of contraception. The subject must agree to continue with the same method throughout the study.
    * having only female sexual partners
    * sexual relationship with sterile male partners only
* Patients diagnosed with COPD stages I-IV as defined by the Global initiative for chronic Obstructive Lung disease (GOLD).

and

* Doctor's diagnosis of acute (onset \< 7 days) moderate exacerbation of COPD defined by a sustained worsening of the patient's condition (including at least 2 of the following symptoms: increased dyspnea, increased sputum production, sputum purulence and increased cough), from the stable state and beyond normal day-to-day variations, necessitating a change in regular medication in patient with underlying COPD, needing additional medical assistance.
* Absence of community acquired pneumonia or lower respiratory tract infection with a clear indication for antibiotic treatment as determined by Procalcitonin level \< 0.25 ng/mL and/or absence of pulmonary infiltrates on routine chest x-ray.
* Smoking history of at least 10 Pack Years or more.
* Patients must be able to complete diaries and quality of life questionnaires.
* Patients must sign and date an informed consent prior to any study procedures.

Exclusion Criteria:

* Severe exacerbation: defined by need for ventilatory support (indicated by severe dyspnea with failure to respond to emergency treatment and/or persistent hypoxemia (PaO2 \<50 mm Hg despite O2 administration and / or respiratory acidosis (pH \<7.35 and PaCO2\> 45mmHg)) or mental confusion or circulatory insufficiency (need of vasopressors)
* Fever (\>38.5°C)
* Known impaired hepatic or renal function
* Active or suspected tuberculosis infection of the respiratory tract
* Acute exacerbation of asthma
* Suspected or known hypersensitivity to, or suspected serious adverse reaction to sultamicillin; suspected or known hypersensitivity to penicillins or cephalosporins
* Immunosuppression or Immunosuppressive therapy (cytostatic chemotherapy within last 28 days or neutropenia (neutrophils \< 1000/µ)l; systemic corticosteroids (≥20 mg prednisolon equivalent/day \> 14 days; HIV-infection; immunosuppression after organ- or bone marrow transplant)- Patients with metastatic or hematological malignancy, splenectomized patients or patients with known hyposplenia or asplenia
* Oral/parenteral antibiotic use within 30 days prior to randomization (a singular administration of antibiotics prior to randomization is allowed)
* In-patient treatment within the last 30 days
* An antibiotic is clearly indicated for treatment of a known infection
* Known MRSA (methicillin-resistant Staphylococcus aureus) colonization or infection
* Patients with known bronchiectasis
* Patients with known bacterial airway colonization (\>3 positive sputum cultures in the previous year)
* Progressively fatal disease, or life expectancy ≤6 months
* Mononucleosis
* Lymphatic leukemia
* Severe gastro-intestinal disorders with vomiting and diarrhea
* Women who are breast feeding
* Patients who have received treatment with any other investigational drug within 1 month prior to study entry, or have such treatment planned for the study period during treatment and follow up phase.
* Patients with mental conditions rendering them unable to understand the nature, scope, and possible consequences of the study.
* Patients unlikely to comply with the protocol, e.g., uncooperative attitude, inability to return for follow up visits, and unlikelihood of completing the study.
D: Inclusion Criteria:

* Male or female out-patients \>/= 45 years
* Subjects suffering from chronic bronchitis
* FEV1\</= 70% and FEV1/FVC \</= 70% predicted from age, height and sex
* No documented episode of AECB (requiring treatment) within 6 weeks of randomization and not experiencing an exacerbation at the time of screening
* Sputum production on most days, even when exacerbation free
* Subjects presented with at least two documented (i.e. requiring antibiotics and/or systemic steroid administration) acute exacerbation episodes during the last 12 monthsIf receiving chronic therapy with inhaled long acting bronchodilators and/or inhaled or systemic steroids, the treatment must have remained stable for the preceding 6 weeks prior to screening
* Smoking history of at least 20 pack-years
* Subjects willing and able to give fully informed written consent

Exclusion Criteria:

* Subjects with contra-indications to moxifloxacin- Known bronchial carcinoma, pulmonary tuberculosis, cystic fibrosis, documented chronic bronchial asthma or diffuse bronchiectasis- Subjects who are actively participating in intensive pulmonary rehabilitation programs
* Subjects with a known history of chronic colonization of pathogenic organisms resistant to moxifloxacin, e.g. Pseudomonas spp, MRSA
* No systemic or inhaled antibiotic therapy during the 6 weeks prior to screening and any long term antibiotic usage
* Subjects requiring home ventilatory support for COPD and those who have a tracheostomy in situ (subjects requiring home/potable oxygen therapy or CPAP for sleep apnea can be included)

Answer: D