Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III Single-blind, Randomised Placebo Controlled Trial of Long Term Therapy in Patients With Stable COPD Using Moxifloxacin, Azithromycin and Doxycycline: a Bayesian Decision Analysis, Including Other Criteria, Will be Used to Distinguish the Optimal Antibiotic Treatment
Brief Summary: Chronic Obstructive Pulmonary Disease (COPD) is the cause of considerable deaths, and exacerbations (flare up of symptoms) are a major cause of hospital admission in the UK. Bacterial infections play an important role in the development of COPD, however, there is little information available about the use of long term antibiotics in the treatment of this disease. Therefore the purpose of this study is to identify the best antibiotic regime for treating patients with COPD who have persistent bacterial infection in their lung. We will test a variety of approaches including both older and newer regimes prescribed either on a daily basis at a lower dose or in "pulsed" courses (for example, every other day or five days every month). The three antibiotics tested in this study are: moxifloxacin, azithromycin and doxycycline. This is a 13 weeks study conducted at the Royal Free Hospital, London. It is expected that approximately 200 patients will be selected for this study. The information we get from this study may help us to treat future patients with COPD better.


Options:
A: Inclusion Criteria:

* Participation in the COPSAC2010 cohort
* recurrent wheeze
* and others

Exclusion Criteria:

* Macrolide allergy
* Heart, liver or kidney disease.
* and others
B: Inclusion Criteria:

* 12-71 months of age.
* Recurrent significant wheezing in the past year (any of the following):

  * \>3 episodes, ≥1 of which was clinically significant\*; OR
  * \>2 clinically significant\* episodes; OR
  * \>4 months of daily controller therapy AND \>1 clinically significant\* episode.
  * \* Clinically significant episode: requiring any of the following: (1) systemic corticosteroids (oral or injectable), (2) unscheduled physician office visit, (3) ED visit, (4) urgent care visit, or (5) hospitalization.
* Up to date with immunizations, including varicella (unless the subject has already had clinical varicella). If the subject needs varicella vaccine, this will be arranged with the primary care physician and must be received prior to randomization.
* Willingness to provide informed consent by the child's parent or guardian.

Exclusion Criteria:

Participants who meet any of the following criteria are NOT eligible for enrollment, but may be re-enrolled if these exclusion criteria are resolved:

* \>4 courses of systemic corticosteroids in past 12 months.
* More than 1 hospitalization for wheezing illnesses within the preceding 12 months.
* Use of long-term controller medications for asthma, including inhaled corticosteroids, leukotriene modifiers, cromolyn/nedocromil, or theophylline for more than 8 months (cumulative use) in the past 12 months.
* Current use of higher than step 2 NAEPP asthma guideline therapy (e.g. medium-high dose ICS alone or combination therapy of low-medium-high dose ICS + LABA, montelukast, theophylline or cromolyn). NOTE: children who have evidence of well-controlled symptoms immediately preceding study entry while receiving Step 2 controller therapy (presence of self-reported symptoms on average no more than 2 times per week and less than 2 nights per month of nocturnal awakenings, requiring albuterol, during the 4 weeks preceding visit 1) may be enrolled and will have their controller therapy discontinued upon study entry.
* Use of OCS in the past 2 weeks.
* Daily symptoms or \>2 nocturnal awakenings, requiring albuterol, on average in the last 2 weeks.
* Use of antibiotics in the past month.
* Current treatment with antibiotics for diagnosed sinus disease.
* Participation presently or in the past month in another investigational drug trial.
* Evidence that the family may be unreliable or nonadherent, or may move from the clinical center area before trial completion.
* Contraindication of use of systemic corticosteroids or azithromycin.
* Clinically relevant gastroesophageal reflux.
* Concurrent medical conditions other than asthma that are likely to require oral or injectable corticosteroids during the study.
* If receiving allergy shots, change in dose within the past 3 months.

Participants who meet any of the following criteria are NOT eligible for enrollment, and may not be re-enrolled:

* Gestation less than late preterm as defined as birth before 34 weeks gestational age.
* Presence of lung disease other than asthma, such as cystic fibrosis and BPD. Evaluation during the screening process will assure that an adequate evaluation of other lung diseases has been performed.
* Presence of other significant medical illnesses (cardiac, liver, gastrointestinal, endocrine) that would place the study subject at increased risk of participating in the study.
* Immunodeficiency disorders.
* History of respiratory failure requiring mechanical ventilation.
* History of hypoxic seizure.
* History of significant adverse reaction to any study medication ingredient.
* The child has significant developmental delay/failure to thrive, defined as crossing of two major percentile lines during the last year for age and gender. If a child plots less than the 10th percentile for age and gender, a growth chart for the previous year will be obtained from the child's primary care provider.
C: 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
D: Inclusion criteria :

Adult and adolescent (12 years of age or older) participants with a physician diagnosis of asthma for \>=12 months, based on the Global Initiative for Asthma (GINA) 2014 guidelines and the following criteria:

* Participants with severe asthma and a well-documented, regular prescribed treatment of maintenance corticosteroids in the 6 months prior to Visit 1 and using a stable OCS dose (ie, no change of OCS dose) for 4 weeks prior to Visit 1. Participants must be taking 5 to 35 mg/day of prednisone/prednisolone, or the equivalent, at Visit 1 and at the randomization visit. In addition, the participants must agree to switch to study-required prednisone/prednisolone as their OCS and use it per protocol for the duration of the study.
* Existing treatment with high-dose inhaled corticosteroid (ICS; \>500 mcg total daily dose of fluticasone propionate or equivalent) in combination with a second controller (ie, long-acting beta agonist \[LABA\], leukotriene receptor antagonist \[LTRA\]) for at least 3 months with a stable dose of ICS for \>=1 month prior to Visit 1. In addition, participants requiring a third controller for their asthma are considered eligible for this study, and it should also be used for at least 3 months with a stable dose \>= 1 month prior to Visit 1.
* A forced expiratory volume in 1 second (FEV1) \<80% of predicted normal for adults and \<=90% of predicted normal for adolescents at Visit 1.
* Evidence of asthma as documented by either: reversibility of at least 12% and 200 mL in FEV1 after the administration of 200 to 400 mcg (2 to 4 inhalations of albuterol/salbutamol or levalbuterol/levosalbutamol, or of a nebulized solution of albuterol/salbutamol or levalbuterol/levosalbutamol, if considered as a standard office practice) before randomization or documented in the 12 months prior to Visit 1 OR airway hyperresponsiveness (methacholine: provocative concentration that causes a positive reaction \[PC20\] of \<8 mg/mL) documented in the 12 months prior to Visit 1.

Exclusion criteria:

* Participants \<12 years of age or the minimum legal age for adolescents in the country of the investigative site, whichever is higher (for those countries where local regulations permit enrollment of adults only, participant recruitment will be restricted to those who were \>=18 years of age).
* Participants who weighed \<30.0 kg.
* Chronic obstructive pulmonary disease (COPD) or other lung diseases (eg, idiopathic pulmonary fibrosis, Churg-Strauss Syndrome, allergic bronchopulmonary aspergillosis, cystic fibrosis) which may impair lung function.
* Clinical evidence or imaging (eg, chest X-ray, computed tomography, magnetic resonance imaging) within 12 months of Visit 1 with clinically significant findings of lung disease(s) other than asthma, as per local standard of care.
* A participant who experiences a deterioration of asthma that results in emergency treatment or hospitalization within 4 weeks of Screening Visit 1.
* A participant who requires 12 puffs or more of rescue medication on any 1 day in the week prior to Visit 1.
* A participant who has experienced an upper or lower respiratory tract infection within the 4 weeks prior to screening.
* Current smoker or cessation of smoking within 6 months prior to Visit 1.
* Previous smoker with a smoking history \>10 pack-years.
* Comorbid disease that might interfere with the evaluation of the investigational medicinal product.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Answer: C