"Tiotropium and Outcomes in Chronic Obstructive Pulmonary Disease". The New England Journal of Medicine. 2008. 359(15):1543-1554. PubMed
Links to original sources: Wiki Journal Post Full Journal Article
Contents 1 Clinical Question 2 Bottom Line 3 Major Points 4 Guidelines 5 Design 6 Population 6.1 Inclusion Criteria 6.2 Exclusion Criteria 6.3 Baseline Characteristics 7 Interventions 8 Outcomes 8.1 Primary Outcome 8.2 Secondary Outcomes 9 Funding 10 Further Reading
In patients with chronic obstructive pulmonary disease (COPD), does long-term therapy with tiotropium improve clinical outcomes?
In patients with COPD, therapy with tiotropium over a 4-year period improved lung function, quality of life, and exacerbations but did not significantly slow the rate of decline in FEV1.
Earlier studies suggested that tiotropium might slow the rate of decline in FEV1 in patients with COPD. The Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial aimed to investigate whether tiotropium would reduce FEV1 decline over a 4-year period while allowing other respiratory medications except other inhaled anticholinergic drugs.
As of the time of the study, guidelines did not specifically recommend the use of tiotropium for altering disease progression, though it may be used for symptomatic relief.
- Multicenter, double-blind, placebo-controlled, parallel-group trial - N=5,993 patients with moderate-to-very-severe COPD - Tiotropium (n=2,987) vs. Placebo (n=3,006) - Setting: 490 investigational centers in 37 countries - Enrollment: January 2003 to March 2004 - Analysis: Intention-to-treat - Follow-up: 4 years - Primary outcome: Yearly rate of decline in mean FEV1 before and after bronchodilation from day 30 until completion of double-blind treatment
Inclusion Criteria - Diagnosis of COPD - Age ≥40 years - Smoking history of ≥10 pack-years - Postbronchodilator FEV1 ≤70% predicted and FEV1/FVC ratio ≤70% after bronchodilation
Exclusion Criteria - Asthma history - COPD exacerbation or respiratory infection within 4 weeks before screening - History of pulmonary resection - Use of supplemental oxygen >12 hours/day - Coexisting illness impacting participation or results
Baseline Characteristics - Mean age: 65±8 years - 75% male, 30% current smokers - Mean postbronchodilator FEV1: 1.32±0.44 liters (48% predicted)
- Patients received either 18 μg of tiotropium or matching placebo once daily delivered through the HandiHaler inhalation device
Primary Outcome - No significant differences between groups in the rate of decline in the mean FEV1 before or after bronchodilation from day 30 to the end of the study-drug treatment
- Tiotropium group maintained mean FEV1 and FVC improvements throughout the trial compared to placebo (P<0.001) - SGRQ scores were better in the tiotropium group throughout the 4-year period (P<0.001) - Delay in time to the first exacerbation and hospitalization for an exacerbation with tiotropium
Supported by Boehringer Ingelheim and Pfizer.
- For a list of investigators involved in the UPLIFT trial, see Supplementary Appendix 1.