SPIRIVA in Ususal Care

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title: A Randomised, Double-blind, Parallel Group, 12 Week Study, Comparing the Effect of Once Daily Tiotropium Lactose Capsule With Placebo in Patients With Chronic Obstructive Pulmonary Disease (COPD), naïve to Anticholinergic Agents in Addition to Receiving Their Usual COPD Care

Status Completed

Clinical Trial Summary

The objective of the study is to determine the effect on lung function when either SPIRIVA once daily or placebo once daily is added to the usual therapy (care) of COPD patients naïve to anticholinergic agents managed in primary care. Previous studies have been in both hospital in and outpatients, with washout of some respiratory medications, this is the first study to be conducted in General Practice, the drug's anticipated environment.

Data from this study, including the adverse event monitoring, and post study findings on physical examination, will be used to extend the safety database. Health Resource Utilisation (HRU) data will be recorded to be use with data from other sources for economic analysis of COPD treatment.

Clinical Trial Description

Anticholinergic drugs are currently indicated for all severities of COPD, due to the dominance of cholinergic tone in the pathological process of the disease. SPIRIVA is a new long acting anticholinergic, which has showed the benefits of improved lung function, dyspnoea, health status and less exacerbations compared to ipratropium, salmeterol and placebo in secondary care (hospital setting). The study will determine if the same effect is seen on the on lung function and dyspnoea when either SPIRIVA or placebo is added to the usual therapy /care of COPD patients naïve to anticholinergic agents managed in primary care.

The one year placebo and active controlled studies have confirmed efficacy and safety. No evidence of tolerance to the bronchodilator effects of tiotropium has been seen. Consistent improvements of health outcomes were also demonstrated. In the one-year studies, statistically significantly fewer patients in the tiotropium groups experienced exacerbations, or were hospitalised for exacerbations. Additionally, time to first exacerbation was increased. This suggests that moderate and severe exacerbations are reduced in-patients treated with tiotropium. The mechanism underlying this is not known, but may be associated with sustained airway opening.

The study will involve five visits to the GP surgery over a period of 14 weeks. Patient will attend for an initial visit to have the study information given to them and obtain their written consent. At the subsequent screening visit a physical examination including ECG together with an assessment of lung function will be performed. Once eligibility to the study is confirmed, and after completion of a 14 day 'run-in' period, patients will start treatment with a daily inhalation from the HandiHaler device of either SPIRIVA or placebo, this in addition to their usual COPD therapy.

Throughout the 12 week treatment period, patients will be required to inhale their study treatment medication (each morning) and complete a diary card. Patients will be required to return to the surgery after 2 and 6 weeks, with the final visit at 12 weeks for lung function testing, assessment of symptoms using the Oxygen Cost Diagram (OCD), Health Resources Utilisation (HRU) and any adverse events. On completion of the 12 week treatment period, a full physical examination will be repeated. Adverse event monitoring including COPD exacerbations will take place throughout the study.

Study Hypothesis:

Based on previous studies on COPD patients who were not on long acting beta agonists (LABAs), the standard deviation (SD) for trough FEV1 was 215 ml and an effect of 130 ml was seen on mean trough FEV1 with tiotropium.

It is assumed that 20% of primary care managed COPD patients will be using LABAs as part of their usual care. The effect of tiotropium on mean trough FEV1 in the study population is expected to be lower than the 130 ml seen in previous studies. Placebo is not expected to have any effect on mean trough FEV1.

Assuming an SD of 235ml, a total of 348 patients (174 per group) is adequate to detect a difference of 100 ml in mean trough FEV1 response between treatments with at the least 95% power at the 2.5% level of significance (one-sided) using a two group t-test.

To be considered complete, a patient must complete all primary efficacy data for all study visits as specified in the protocol without violations of the protocol so significant as to obscure the response to treatment.

Comparison(s):

Usual care for COPD ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Pulmonary Disease, Chronic Obstructive

• NCT number: NCT00274079
• Study type: Interventional
• Source: Boehringer Ingelheim
• Status: Completed
• Phase: Phase 4
• Start date: October 2002
• Completion date: October 2003