Please select the eligibility criteria that correspond to the clinical trial below.
Title: Proof of Concept Study to Investigate the Impact of Azithromycin Administered iv Versus Placebo on the Prevention of Pneumonia in Ventilated Patients Colonized by Pseudomonas Aeruginosa
Brief Summary: The purpose of this study is to assess the clinical efficacy of azithromycin, used as a quorum-sensing blocker, when compared to placebo for preventing or delaying the occurrence of pneumonia in ventilated patients colonized with Pseudomonas aeruginosa.


Options:
A: 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
B: Inclusion Criteria:

* Have provided written informed consent to participate in the study in accordance with the local ethics committee regulations
* Have a confirmed diagnosis of bronchiectasis (by HRCT) Aged 18 years or over Have chronic sputum production, defined as a greater than 45 mililitres volume produced in the 1 week prior to study entry.
* Be able to perform reproducible spirometry
* Be in a relatively stable disease state in the 6 weeks prior to entry, as defined by the absence of the following: respiratory exacerbations requiring hospitalisation, change in cough and/or sputum production, new or increased hemoptysis, more than 10% weight loss, use of additional antibiotic courses

Exclusion Criteria:

* Subjects will be excluded if one or more of the following criteria occur. The subject: Is an investigator, or an immediate family member of an investigator
* Has a confirmed diagnosis of cystic fibrosis, as evidenced by genetic analysis or a sweat test result more than 60mmol/L
* Has a primary immunodeficiency Is a pregnant or lactating female Has had a respiratory exacerbation requiring hospitalisation or additional course of antibiotics in the 6 weeks prior to study entry
* Has been prescribed or used oral steroids on any occasion for the 3 months prior to study entry.
* Has been using mucolytic agents on any occasion for the 2 months prior to study entry Has active tuberculosis
* Has an active malignancy, including melanoma (other skin carcinomas excluded)
* Has a history of significant liver disease or insufficiency Has a significant history of drug abuse (including alcohol abuse) or mental illness Has a known intolerance or allergy to macrolides
* Has been participating in another interventional drug study in the 3 months prior to enrolment into this study
C: Inclusion Criteria:

* Bronchiectasis confirmed by HRCT of the chest
* Clinically stable (not requiring antibiotics for at least 4 weeks preceding the study start date)
* Aged 18-70
* Chronic sputum production \> 5 mls for the majority of days in 3 months before enrolment
* Chronically colonized (on at least 2 occasions in the preceding 12 months) whilst clinically stable
* At least two exacerbations in the past year
* Patients able to tolerate a nebulized gentamicin challenge
* FEV1 \> 30% predicted
* Smoking \< 20 pack year history and ex-smokers \>1 year.

Exclusion Criteria:

* Cystic fibrosis
* Emphysema on HRCT chest
* Thoracic surgery within the past 1 year
* Allergic bronchopulmonary aspergillosis
* Poorly controlled asthma ( \> 20% diurnal variation in peak expiratory flows despite treatment)
* Unstable angina or uncontrolled congestive cardiac failure
* Active malignancy
* Pregnancy or breast feeding
* Creatinine clearance \< 30 mls/minute
* Vestibular instability
* Previous documented intolerance to aminoglycosides
D: Inclusion Criteria:

* Male and non pregnant female aged 18 to 75 years
* Patients hospitalized in ICU, under mechanically assisted ventilation expected to be mandatory for 3 days or more
* Reasonable survival chance within next few days with an Apache score 10-25
* Tracheal aspirate found positive for P. aeruginosa
* The subject (or a close family member in case of incompetence) understands the procedure, agrees to participate, and is willing to give written informed consent
* Informed consent must be obtained for all subjects before enrollment in the study, by patient or by a close family member

Exclusion Criteria:

* Poor prognosis as judged by Apache score II score \>25
* Pregnant female
* Grossly under-or overweight (BMI\<18or \>29)
* Ongoing therapy with a macrolide
* Known allergy to any macrolide
* Proven P. aeruginosa pneumonia
* Ongoing anti-pseudomonal therapy with a proven susceptible colonizing strain
* Anticipated short duration of mechanical ventilation (\<3 days)
* Known drug interaction that could either decrease efficacy or raise safety concerns
* Severe hepatic failure (type C, score \>10 on Child Pugh scale)
* Sick sinus syndrome or long QT syndrome
* Recent donation of blood or participation in another clinical trial within 3 months
* Any situation exposing the patient to higher risk or possibly confounding results

Answer: D