Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-blind, Placebo-controlled, Parallel Group Trial Assessing the Proportion of Patients Experiencing an Exacerbation and Proportion of Patients Hospitalized for an Exacerbation Over 6 Months During Treatment With Tiotropium 18 Mcg Capsule Once Daily in Patients With COPD in a Veterans Affairs Setting
Brief Summary: The primary objective of this trial is to determine whether treatment with tiotropium (18 mcg) capsule once daily via the HandiHaler reduces the proportion of patients with COPD experiencing an exacerbation and the proportion of patients hospitalized for an exacerbation during a six month observation period.


Options:
A: Inclusion criteria:

1. All patients must sign an informed consent consistent with International Conference on Harmonization Good Clinical Practice (ICH-GCP) guidelines prior to participation in the trial, which includes medication washout and restrictions.
2. Male or female patients 40 years of age or older.
3. Patients must be current or ex-smokers with a smoking history of ≥10 pack-years. (Patients who have never smoked cigarettes must be excluded)
4. All patients must have a diagnosis of COPD (P06-12085), and must meet the following criteria: Relatively stable airway obstruction with a post-bronchodilator FEV1 ≤ 70% of predicted normal and post-bronchodilator FEV1 / FVC ≤70%.

   Pulmonary function tests (PFTs) were conducted after the inhalation of 400 μg salbutamol / albuterol (preferred), however testing with either 200 μg salbutamol/albuterol or a combination of salbutamol / albuterol with ipratropium bromide (2 to 4 actuations) was acceptable. Other short-acting beta agonists, such as terbutaline, may have been used for the testing. The medication used for the testing was documented. Further, historical data from measurements within the past 6 months either at the site or at a referral site may have been used (see Section 6.2.1 of the CTP, located in Appendix 16.1.1). Subjects were not to have been randomized to the study without the availability of spirometry data at the actual study site.

   Eligibility for PFT sub-study: For subjects participating in the spirometry sub-study, historical data may not have been used for inclusion. These subjects must have qualified in the clinic at Visit 1 after performing a baseline measurement. These subjects performed a pre-dose PFT which was followed by the administration of 400 μg salbutamol / albuterol only (no other short-acting beta agonist was allowed), followed by a post-dose PFT for qualification.
5. Able to inhale from the HandiHaler® and the Respimat® devices.

Exclusion criteria:

1. Significant diseases other than COPD. A significant disease is defined as a disease or condition which, in the opinion of the investigator, may put the patient at risk because of participation in the study or may influence the patients ability to participate in the study.
2. Patients with a recent history (i.e., six months or less) of myocardial infarction.
3. Patients with any unstable or life-threatening cardiac arrhythmia requiring intervention or change in drug therapy during the last year.
4. Hospitalisation for cardiac failure (New York Heart Association (NYHA) Class III or IV) during the past year.
5. Known active tuberculosis.
6. Patients with a history of asthma, cystic fibrosis, clinically evident bronchiectasis, interstitial lung disease, or pulmonary thromboembolic disease.
7. History of thoracotomy with pulmonary resection. Subjects with a history of thoracotomy for other reasons were to have been evaluated per exclusion criterion 1.
8. Subject was planning to undergo lung transplant or lung volume reduction surgery (LVRS).
9. Malignancy for which the subject had undergone resection, radiation, chemotherapy or biological treatments within the last 5 years. Subjects with treated basal cell carcinoma were allowed.
10. Known respiratory infection or exacerbation of COPD in the 4 weeks prior to randomization.
11. Known hypersensitivity to anticholinergic drugs, lactose, benzalkonium chloride (BAC), ethylenediaminetetraacetic acid (EDTA), or any other components of the HandiHaler® or Respimat® inhalation solution delivery system.
12. Known moderate to severe renal impairment (as judged by the investigator).
13. Known narrow angle glaucoma.
14. Known significant symptomatic prostatic hyperplasia or bladder-neck obstruction. Subjects whose symptoms were controlled on treatment may have been included.
15. Use of systemic corticosteroid medication at unstable doses (i.e., less than 6 weeks on stable dose) or at doses in excess of the equivalent of 10 mg prednisolone per day.
16. Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception for at least 3 months prior to and for the duration of the trial.
17. Significant alcohol or drug abuse within the past 12 months.
18. Subjects requiring the use of supplemental oxygen therapy for \> 12 hours per day.
19. Subjects who had completed a pulmonary rehabilitation program in the 6 weeks prior to the screening visit or subjects who were currently in a pulmonary rehabilitation program that was not maintained throughout the duration of the study.
20. Subjects who had taken an investigational drug within 30 days prior to the Screening Visit.
21. Previous participation (receipt of randomized treatment) in this study.
22. Subjects who were currently participating in an interventional study.
B: Inclusion Criteria:

1. All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria:

   * Patients must have relatively stable, mild to severe airway obstruction with an FEV1 =\<70% of predicted normal and an FEV1/FVC \< 70 %.
   * Predicted normal values will be taken from the print-outs of the spirometers. Spirometers have to calibrated according to ECCS.
2. Male or female patients 40 years of age or older.
3. Patients must be current or ex-smokers with a smoking history of 10 or more than 10 pack-years. Pack Years = Number of cigarettes/day : 20 x years of smoking (Patients who have never smoked cigarettes must not be included)
4. Patients must be able to perform all study related tests, acceptable pulmonary function tests, including Peak Expiratory Flow Rate (PEFR) measurements, and must be able to maintain diary cards during the study period as required in the protocol.
5. Patients must be able to inhale medication from the HandiHaler.
6. All patients must sign an Informed Consent Form prior to participation in the trial i.e. prior to pre-study washout of their usual pulmonary medications.

Exclusion Criteria:

1. Patients with significant diseases other than COPD will be excluded. A significant disease is defined as a disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study.
2. Patients with a recent history (i.e., one year or less) of myocardial infarction.
3. Patients with any cardiac arrhythmia requiring drug therapy or who have been hospitalised for heart failure within the past three years.
4. Patients who regularly use daytime oxygen therapy for more than 1 hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy.
5. Patients with known active tuberculosis.
6. Patients with a history of cancer within the last five years. Patients with treated basal cell carcinoma are allowed.
7. Patients with a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis.
8. Patients who have undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated as per exclusion 1.
9. Patients with any respiratory infection in the past six weeks prior to the Screening Visit (Visit 1) or during the run-in period.
10. Patients who are currently in a pulmonary rehabilitation programme or who have completed a pulmonary rehabilitation programme in the six week prior to the Screening Visit (Visit 1).
11. Patients with known hypersensitivity to anticholinergic drugs, lactose or any other components of the inhalation capsule delivery system.
12. Patients with known symptomatic prostate hypertrophy or bladder neck obstruction.
13. Patients with known narrow-angle glaucoma.
14. Patients using oral corticosteroid medication at unstable doses (i.e., less than four weeks on a stable dose before Visit 1) or at doses in excess of the equivalent of 10 mg of prednisolone per day or 20 mg every other day.
15. Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (i.e. oral contraceptives, intrauterine devices, diaphragm or subdermal implants).
16. Patients with a history of asthma, allergic rhinitis or atopy.
17. Patients with a history of and/or active significant alcohol or drug abuse.
18. Patients who have taken an investigational drug within one month prior to Screening Visit (Visit 1). A log of all subjects screened, and reasons for exclusion for those not randomised will be maintained.
C: N/A
D: Inclusion Criteria:

* Adult male and female patients aged 40 with stable moderate to severe COPD (GOLD guidelines).
* Post-salbutamol (FEV1) \< 80% and ≥ 30% of predicted normal value and Post-salbutamol FEV1/FVC \< 70%.
* Current or ex smokers of 10 pack-years.

Exclusion Criteria:

* Patients with no history or current diagnosis of asthma.
* No evidence of an exacerbation within 6 weeks prior to the screening visit.
* No evidence of clinically significant respiratory and/or cardiovascular conditions or laboratory abnormalities.
* No contraindication to use of anticholinergic drugs such as known symptomatic prostatic hypertrophy, bladder neck obstruction or narrow-angle glaucoma.

Answer: C