Tiotropium (18mcg) in Chronic Obstructive Pulmonary Disease (COPD) Patients With a Respiratory Infection

A 12-week, Randomised, Placebo-controlled, Double-blind, Parallel Group, Multi-center Trial to Assess the Efficacy and Safety of Tiotropium Bromide (18 µg) Delivered Via the HandiHaler® in Patients With Newly Diagnosed and/or Maintenance Treatment naïve Chronic Obstructive Pulmonary Disease (COPD) Experiencing an Acute Respiratory Infection (TICARI 1: Tiotropium In COPD Patients With an Acute Respiratory Infection 1)

The aim of the study is to investigate whether the early introduction of maintenance bronchodilator therapy during an acute symptomatic episode of the disease shows benefits on the recovery of symptoms. It also represents an opportunity to identify COPD patients earlier in their disease state and start maintenance therapy, if appropriate.

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 and conducting any study procedures.
2. Male or female patients 40 years of age or older.
3. Ability to independently read and understand English and/or Spanish.
4. Any self-reported history of smoking (e.g. = 100 cigarettes (~5 packs) during life-time).
5. Acute respiratory symptoms for up to 7 days
6. All patients must have a diagnosis of COPD, and must have an airway obstruction with a post-bronchodilator (Forced Expiratory Volume in 1 second (FEV1)/Forced Vital Capacity (FVC)) <0.7. The diagnosis of COPD can be made at Visit 1.
7. The clinical assessment of the enrolled patient in the judgement of the investigator supports the introduction of COPD maintenance therapy.
8. Patients must be able to inhale medication in a competent manner from the HandiHaler® device and from a metered dose inhaler (MDI)

Exclusion criteria:

1. Therapy with any long-acting bronchodilator, short-acting anticholinergic, inhaled corticosteroid or regular maintenance use (>14 consecutive days) of systemic corticosteroid (the latter for respiratory indications) during the previous 6 months (short course of systemic corticosteroid for up to 14 days for respiratory indications allowed); in case of use of systemic corticosteroid medication for other than respiratory conditions, then exclusion of unstable doses (i.e., less than six weeks on stable dose) or at doses in excess of the equivalent of 10 mg prednisolone-equivalent per day. In addition, daily use of short-acting beta2-agonist for more than a week prior to Visit 0 not allowed.

   The following exclusion criteria apply at Visit 1:

2. 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 patient¿s ability to participate in the study.

3. A recent history (i.e., six months or less) of myocardial infarction. Patients being stable with a history of cardiac stents prior to six month are permitted.

4. Any unstable or life-threatening cardiac arrhythmia requiring intervention or change in drug therapy during the last year.

5. Hospitalisation for cardiac failure (New York Heart Association (NYHA) Class III or IV) during the past year.

6. Any significant or new ECG findings at V1 as judged by the investigator, including, but not limited to signs of ischemia, arrhythmia, heart failure, or the report of chest pain.

7. Known active tuberculosis.

8. Current asthma (patient treated for asthma in the last 2 years), cystic fibrosis, clinical diagnosis of bronchiectasis, interstitial lung disease, or pulmonary thromboembolic disease.

9. A history of thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion no. 2.

10. Malignancy for which the patient has undergone resection, radiation, chemotherapy or biological treatments within the last year or is currently on active radiation therapy, chemotherapy or biological treatment. Patients with treated basal cell carcinoma are allowed.

11. At visit 0 or 1, a severe respiratory infection, e.g. pneumonia (as suspected by investigator), any condition or exacerbation requiring ER visit or hospitalization, need for oxygen treatment.

12. Known hypersensitivity to anticholinergic drugs, lactose, or any other components of the HandiHaler® or MDI inhalation solution delivery system.

13. Treatment with any restricted pulmonary medication

14. Requirement of supplemental oxygen therapy for = 24 hours during the previous 6 months.

15. Known moderate to severe renal impairment.

16. Known narrow angle glaucoma.

17. Significant symptomatic prostatic hyperplasia or bladder-neck obstruction. Patients whose symptoms are controlled on treatment may be included.

18. 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 e.g., Norplant®) for at least three months prior to and for the duration of the trial.

19. Significant alcohol or drug abuse within the past 12 months.

20. Actively participating in a pulmonary rehabilitation program.

21. Previously randomized in this study or currently participating in another interventional study.

22. Visual impairment that as judged by the investigator does not allow the patient to independently read and complete the questionnaires and electronic diary (eDiary).