First Comprehensive Results From The UPLIFT Trial Revealed At The ERS Annual Congress In Berlin - Authors Reaffirm Tiotropium's Safety

Main Category: COPD
Also Included In: Clinical Trials / Drug Trials
Article Date: 06 Oct 2008 - 2:00 PDT

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The UPLIFT (Understanding Potential Long-term Impacts on Function with Tiotropium) study is a randomized double-blind, parallel-group, 4-year trial. One of the largest COPD trials ever undertaken, UPLIFT was aimed at comparing treatment with tiotropium once daily to placebo in COPD patients.

It involved 5,993 patients, aged 65±8 years, with a FEV1 of 1.32± 0.44 L, followed in 470 sites and 37 countries. Three out of four patients were men and 30% current smokers.

Patients were randomised 1:1 to receive either 18 mg tiotropium or placebo once daily. In both arms, patients were allowed to continue with their normally prescribed respiratory medications, including dose adjustments throughout the trial, except inhaled anticholinergics.

As presented at the 18th Annual Congress of the European Respiratory Society (ERS) in Berlin on Sunday, exploratory modelling of UPLIFT's data, accounting for the time during the treatment period when patients were not on inhaled steroids or long-acting beta-agonists, shows a difference in rate of decline of FEV1 of 10.1 ± 3.8 mL/yr. (p=0.008) in favor of tiotropium. In addition, according to the results presented to the ERS Congress participants, tiotropium significantly reduces the risk of exacerbations leading to hospitalisations, versus the control group.

Yet, the UPLIFT trial shows no treatment differences in the rate of decline of trough or postbronchodilator FEV1.

Discontinuation rate was 45% in the placebo group, versus 36% among the patients on tiotropium (p<0.001).

The investigators of the study, which was simultaneously published on-line ahead of print by the New England Journal of Medicine on Sunday, announced in Berlin that mean FEV1 and FVC showed statistically significant improvements, and that these improvements were maintained throughout the trial.

Moreover, as tiotropium reduced the risk of COPD exacerbations by 14% (95%CI) and the risk of respiratory failure by 33%, all cause mortality during the treatment period was reduced by 16%.

Tiotropium maintained improvements of lung function and health status over four years, reduced exacerbations, decreased reports of respiratory failure and improved survival, concluded the investigators at the ERS Annual Congress.

As a recently released meta-analysis, published in the Journal of the American Medical Association (JAMA, vol.300, No 12, September 24), pointed to the question of cardiovascular risk associated with inhaled anticholinergics, the authors of the UPLIFT study were keen to reaffirm that they consider tiotropium as a safe drug.

Considering that COPD currently affects more than 200 million people and that tiotropium provides to most of them a significant improvement in lung function, it is important to assure doctors and their patients that the drug is a safe and effective medication, they added.

"Thanks to its Annual meeting, which is now the world's largest congress in respiratory medicine and currently attracting more than 18,500 respiratory professionals from more than 100 countries, the ERS is able to provide the best platform ever to discuss this issue", emphasized Leonardo Fabbri, ERS President.

European Respiratory Society

European Respiratory Society Annual Congress