Long-term mortality follow-up of the ISOLDE participants: causes of death during 13 years after trial completion.

The Inhaled Steroids in Obstructive Lung Disease (ISOLDE) study was a trial that randomised 752 patients with moderate to severe COPD to fluticasone propionate 1000 mcg/day or placebo for three years. We aimed to examine the causes of death of the ISOLDE participants after the original three up to 13 years post-randomisation. Death certificates were obtained either from the NHS Strategic Tracing Service or from the Office of National statistics. Deaths were classified according to the trial protocol. In the subsample of 375 participants from the seven ISOLDE original centers where complete extended follow-up was conducted, the factors associated with observed higher mortality (p<0.05) were male gender, older age and more severe COPD. Causes of death were; 107 (52%) respiratory, 38 (18%) cardiac, 29 (14%) lung cancer, 16 (8%) other cancer and 16 (8%) other causes. The percentage of respiratory-related deaths increased during the follow-up period; from 46% within the three-year trial, to 48% after 3-6 years, 57% after 6-9 years, and 60% after 9-13 years of follow-up (p for trend<0.05). We conclude that participants' survival is poor (only 44% in the 13 years after the ISOLDE trial), and that respiratory-related illnesses were the most frequent causes of death in patients with moderate to severe COPD.