Use of the novel composite endpoint known as COPDCompEx may be able to predict treatment effect on moderate to severe exacerbations of chronic obstructive pulmonary disease (COPD), thus allowing shorter phase 2 clinical trials requiring fewer patients compared with current studies. A post hoc analysis was conducted using data from 20 randomized controlled trials (RCTs) to test and develop COPDCompEx, and results were published in the journal Respiratory Medicine.
Investigators sought to explore the utility of COPDCompEx as an assessment tool in patients with COPD. In this analysis, diary events were examined against predefined threshold values for peak expiratory flow, use of reliever medications in both the morning and the evening, and patients’ symptoms. Symptoms included individual domain scores for the Breathlessness, Cough, and Sputum Scale, along with wheeze and chest tightness. Symptoms experienced by patients were captured mostly in patients’ diaries in the evening, with sleep disturbance symptoms described in the morning. A COPDCompEx event was defined as any first occurrence of a diary event, a study dropout, or a moderate or severe exacerbation of COPD. Ratios of frequency of events, treatment effect, and future sample size were compared between COPDCompEx and moderate and severe COPD exacerbations.
Data from the 20 RCTs yielded a total analytical dataset of 18,442 patients with moderate to very severe COPD. The COPDCompEx development dataset included a total of 6260 patients with a history of 1 or more COPD exacerbations during the previous 12 months; the COPDCompEx test dataset included a total of 12,182 patients.
To develop COPDCompEx, data were included from 8 studies conducted over a period of 3 to 12 months that evaluated the effect of maintenance therapy with budesonide and formoterol in a combination inhaler. Further, COPDCompEx performance was tested in data from an additional 12 studies also conducted over a period of 3 to 12 months in patients with moderate to very severe COPD.
Findings from the study showed that at 3 months, the percentage of patients who experienced COPDCompEx events increased more than 3-fold compared with exacerbations alone. All of the components evaluated contributed to the COPDCompEx event rate. Treatment effects at 3 months were closely matched between COPDCompEx and exacerbations of COPD, with the large net gain in power considerably reducing the required sample size.
The investigators concluded that the use of COPDCompEx may help to predict the therapeutic effect on moderate to severe COPD exacerbations, thus enabling the use of shorter phase 2 clinical trials that would require fewer patients, with exacerbations being a key phase 3 endpoint. This would permit more efficient decision making as well as a decreased burden and risk to study participants.