Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effect of Chronic Macrolide Administration on the Frequency and Severity of COPD Exacerbations
Brief Summary: The purpose of this study is to determine if long-term administration of a macrolide antibiotic will reduce worsening of symptoms among individuals with chronic obstructive pulmonary disease (COPD).


Options:
A: Inclusion Criteria:

* Confirmed COPD diagnosis
* Informed Consent: Patients must give their signed and dated written informed consent to participate
* Gender: Male or female patients
* Age: ≥ 45 years of age at screening
* Produce sputum regularly (produce sputum in at least 3 months of a year)
* Able to complete questionnaires for health status and symptoms and considered able to comply with the dosing regimen.
* Severity of disease: Patients with a measured FEV1\<80% of predicted normal values as determined at screening. An average of three spirometry readings will be taken.

Exclusion Criteria:

* Patients with TB, other chronic respiratory disease (e.g. chronic asthma, bronchiectasis, pulmonary fibrosis), patients with hepatic or renal impairment and patients with prolonged QT interval and other cardiac abnormalities.
* Patients with known hypersensitivity to the antibiotics under evaluation.
* Patients on long term antibiotics for other conditions.
* Patients with uncontrolled hypertension.
* Female patients who are pregnant or planning on becoming pregnant during the study, or are breastfeeding.
* Patients with a history of long QT syndrome or whose QTc measured at Visit 1 is prolonged (\>450 msec for males and females) as confirmed by the ECG assessor.
* Clinically relevant abnormal laboratory values at the screening assessment that could interfere with the objectives of the trial or safety of the volunteer.
* Patient taking clinically significant contraindicated medication, as per the SmPCs
B: Inclusion Criteria:

* Clinical diagnosis of at least moderate Chronic Obstructive Pulmonary Disease (COPD), as defined by the following Global Initiative for COPD (GOLD) criteria:

  1. Post-bronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio of less than 70%
  2. Post-bronchodilator FEV1 less than 80% predicted, with or without chronic symptoms
* Cigarette consumption of 10 pack-years or more (may or may not be active smokers)
* Meets one or more of the following four conditions:

  1. Current, or history of, supplemental O2 use
  2. Received a course of systemic corticosteroids for respiratory problems within 1 year prior to study entry
  3. Visited an emergency department for a COPD exacerbation within 1 year prior to study entry
  4. Hospitalized for a COPD exacerbation within 1 year prior to study entry
* Willing to make return visits
* Available by telephone for duration of study
* Minimum of 4 weeks from the most recent acute exacerbation (have not received a course of systemic corticosteroids, an increased dose of chronically administered systemic corticosteroids, and/or antibiotics for an acute exacerbation for a minimum of 4 weeks from the time of study entry)

Exclusion Criteria:

* Diagnosis of asthma
* Diagnosis other than COPD that results in the patient being either medically unstable, or having a predicted life expectancy less than 3 years
* Special patient groups (i.e., prisoners, pregnant women, or institutionalized patients)
* Women who are at risk of becoming pregnant during the study (pre-menopausal) and who refuse to use acceptable birth control (i.e., hormone-based oral or barrier contraceptive) for the duration of the study
* History of hypersensitivity to any macrolide antibiotic
* Taking any of the following medications:

  1. Cisapride
  2. Ergot derivatives
  3. Pimozide
  4. Disopyramide
  5. Cyclosporin
  6. Tacrolimus
  7. Nelfinavir
  8. Bromocriptine
  9. Hexobarbital
* Corrected QT interval (QTc) on electrocardiogram exceeding 440 ms
* Taking rifabutin or rifampin
* Chronic hepatic insufficiency
* Chronic renal insufficiency
* Diagnosis of bronchiectasis (defined as production of greater than one-half cup of purulent sputum/day)
* If, for either ear, formal audiometric testing in a sound booth results in a pure tone average (i.e., the average of the thresholds for the 4 frequencies 1000, 2000, 3000, or 4000) exceeding 50 decibel (dB), or if the threshold at any one frequency exceeds 60 dB, then the participant will be counseled by the audiologist concerning hearing aids and/or referral to an otolaryngologist. In addition, the audiologist may discuss with the participant whether or not to continue in the study. Following the examination and counseling, the participant will also discuss whether or not to continue in the study with one of the study investigators. If it is found that a participant's pure tone average in the two ears differs by more than 15 dB, or if the difference in the two ears for any one frequency exceeds 20 dB, then the participant will not be eligible for randomization into the study unless cleared by an otolaryngologist
C: Inclusion Criteria:

* Patients \> 40 years of age, in our outpatient clinic with chronic cough and COPD (gold2-4)
* Chronic cough is defined as a cough \> 12 weeks duration, at least 12 weeks a year in 2 subsequent years.
* Analysed for bronchiectasis prior to participation by CT-thorax.

Exclusion Criteria:

* Prior history of asthma
* Use of i.v. or oral corticosteroids and or antibiotics for an exacerbation 3 weeks before inclusion
* Patients suffering from other relevant lung diseases.
* Clinically relevant abnormal laboratory values suggesting an unknown disease requiring further clinical evaluation.
* Liver disease, (ALAT and/or ASAT levels two or more times the upper limit of normal).
* Pregnancy or lactation.
* Use of macrolides the last 6 weeks prior to inclusion.
* Allergy or intolerance to macrolides.
* Other research medication started 2 months prior to inclusion.
* Prior randomisation in this study.
D: Inclusion Criteria:

* Clinical Diagnosis of COPD
* Clinically stable for 6 weeks
* Able to Swallow Tablets

Exclusion Criteria:

* Clinically significant respiratory disease other than COPD
* Women of child bearing age
* Patients receiving existing Medication which may interact adversely with trial drug
* History of clinically significant liver disease

Answer: B