SALT LAKE CITY -- In what is being billed as a landmark trial, a combination of two drugs often used alone has increased survival, quality of life, and lung function in patients with chronic obstructive pulmonary disease, researchers said here.
SALT LAKE CITY, Oct. 24 -- In what is being billed as a landmark trial, a combination of two drugs often used alone has increased survival, quality of life, and lung function in patients with chronic obstructive pulmonary disease, researchers said here.
Combining Flovent (fluticasone propionate) and Serevent (salmeterol) in a single formulation resulted in a 17.5% relative risk reduction in all-cause mortality, compared with placebo, over three years, Bartolome Celli, M.D., of Caritas-St. Elizabeth's Medical Center in Boston reported at CHEST 2006, the meeting of the American College of Chest Physicians.
The benefit eluded statistical significance, however, with a P-value of 0.052, Dr. Celli told reporters here before presenting data from the TOwards a Revolution in COPD Health (TORCH) study.
He conceded that the issue of significance is likely to be a point of controversy. "Is it a positive trial or a negative trial?"
But combined with other analyses, including significant improvements in quality of life, number of exacerbations, and lung function, Dr. Celli said that he is "pretty confident" that the mortality effect is real.
He noted that a Cox proportional analysis of the combination, compared with placebo, showed a hazard ratio for death of 0.811, which was statistically significant at P=0.031. And, he added, the reduction in COPD-related death reached statistical significance.
"To me the signal is strong enough," he said. Doctors with COPD patients should consider prescribing the combination formulation.
The multinational TORCH trial enrolled 6,112 patients with moderate-to-severe COPD and randomized them to one of four arms -- placebo, Flovent alone, Serevent alone, or the combination formulation.
Dr. Celli said the study is a landmark because it is the largest-ever intervention trial in COPD and included patients and investigators from around the world.
Also, Dr. Celli said, "it is the first to show an impact on mortality."
The trial is "one of the single most important trials in respiratory medicine that has been in an awfully long time," commented Ronald Grossman, M.D., of the University of Toronto. In fact, he noted, the 17.5% effect on mortality is probably "a very, very conservative estimate."
The study evaluated patients on an intent-to-treat basis, he said, so that the large number of patients who dropped out of the placebo arm and moved to more effective treatment were counted as failures.
"It's hard to believe it's not a real effect," he said.
For the study, the two drugs were combined at 500 mcg of Flovent and 50 mg of Serevent. GlaxoSmithKline, which sponsored the TORCH trial, sells a slightly different formulation -- 250 mg of Flovent and 50 mg of Serevent -- in the U.S. as Advair, Dr. Celli said.
Dr. Celli said he couldn't comment on what effect, if any, the U.S. formulation might have on mortality and other factors in COPD patients.
In terms of mortality, the two component arms were not significantly different from placebo, Dr. Celli said.
The study also found: