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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: tiotropium
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: 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. Male or female patients 40 years of age or older. Ability to independently read and understand English and/or Spanish. Any self-reported history of smoking (e.g. = 100 cigarettes ( 5 packs) during life-time). Acute respiratory symptoms for up to 7 days 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. The clinical assessment of the enrolled patient in the judgement of the investigator supports the introduction of COPD maintenance therapy. Patients must be able to inhale medication in a competent manner from the HandiHaler® device and from a metered dose inhaler (MDI) Exclusion criteria: 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: 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. 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. Any unstable or life-threatening cardiac arrhythmia requiring intervention or change in drug therapy during the last year. Hospitalisation for cardiac failure (New York Heart Association (NYHA) Class III or IV) during the past year. 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. Known active tuberculosis. Current asthma (patient treated for asthma in the last 2 years), cystic fibrosis, clinical diagnosis of bronchiectasis, interstitial lung disease, or pulmonary thromboembolic disease. 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. 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. 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. Known hypersensitivity to anticholinergic drugs, lactose, or any other components of the HandiHaler® or MDI inhalation solution delivery system. Treatment with any restricted pulmonary medication Requirement of supplemental oxygen therapy for = 24 hours during the previous 6 months. Known moderate to severe renal impairment. Known narrow angle glaucoma. Significant symptomatic prostatic hyperplasia or bladder-neck obstruction. Patients whose symptoms are controlled on treatment may be included. 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. Significant alcohol or drug abuse within the past 12 months. Actively participating in a pulmonary rehabilitation program. Previously randomized in this study or currently participating in another interventional study. Visual impairment that as judged by the investigator does not allow the patient to independently read and complete the questionnaires and electronic diary (eDiary).

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tiotropium 18mcg<br>active | Drug: tiotropium<br>* 18mcg<br>|
| Placebo Comparator: Placebo<br>placebo | Drug: Placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough FEV1 After 12 Weeks on Study Drug | The primary endpoint was trough forced expiratory volume in 1 second (FEV1) after 12 weeks on study drug. Trough forced expiratory volume in 1 second (FEV1)was defined as the FEV1 measurement prior to the next dosing of study drug and approximately 24 hours after the last inhalation of study drug. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Recovery From Acute Respiratory Symptoms | Time to recovery was assessed with the EXACT-PRO questionnaire tool. The EXACT-PRO was designed to collect data to quantify frequency, severity, and duration of exacerbations in patients with COPD including the onset of and the recovery from COPD exacerbations. The EXACT-PRO is a 14-item questionnaire. Each attribute or item was assessed on a five- or six-point ordinal scale and summed to yield a total score that was converted to a 0-100 scale, with higher scores indicating a more severe health state or exacerbation. The EXACT-PRO was answered by the patients on a daily basis in the evening. | 12 weeks | 
| Trough FVC (in Litres) at 12 Weeks | The trough Forced Vital Capacity (FVC) was defined as the FVC measurement prior to the next dosing of study drug and approximately 24 hours after the last inhalation of study drug. | 12 weeks | 
| Responder Status at Week 4 Clinic Visit | Responder status was determined at each clinic visit. The number and percentage of subjects in each of the following 3 classes were presented: Subject recovered without change of therapy (subjects who received an additional course of antibiotics and/or systemic corticosteroids starting after Visit 1 were not included). Subject recovered but had a change in therapy (subject received an additional course of antibiotics and/or systemic corticosteroids starting after Visit 1). Subject did not recover. | 4 weeks | 
| Responder Status at Week 12 Clinic Visit | Responder status was determined at each clinic visit. The number and percentage of subjects in each of the following 3 classes were presented: Subject recovered without change of therapy (subjects who received an additional course of antibiotics and/or systemic corticosteroids starting after Visit 1 were not included). Subject recovered but had a change in therapy (subject received an additional course of antibiotics and/or systemic corticosteroids starting after Visit 1). Subject did not recover. | 12 weeks | 
| Weekly Rescue Medication Use Over the 12 Weeks of Study | Daily rescue albuterol use was recorded in the diary in response to the following question: How many puffs of rescue medication did you use during the last 24 hours? The weekly rescue medication use was derived by summing the daily uses over the 12 weeks and dividing this total by 12 weeks. | 12 weeks |