COPD · Triple versus dual therapy
Efficacy and Safety of Triple Therapy in Obstructive Lung Disease
| Design | Phase 3, double-blind, parallel-group RCT with four arms |
|---|---|
| Treatment | Budesonide 320 microg or 160 microg with glycopyrrolate 18 microg and formoterol 9.6 microg, twice daily |
| Control | Glycopyrrolate/formoterol, or budesonide/formoterol |
| Population | 8509 patients with moderate-to-very-severe COPD and at least one exacerbation in the past year |
| Follow-up | 52 weeks |
| Primary endpoint | Annual rate of moderate or severe COPD exacerbations |
| Result | 1.08 per year with 320 microg budesonide triple therapy and 1.07 with 160 microg, versus 1.42 with glycopyrrolate/formoterol and 1.24 with budesonide/formoterol. Against glycopyrrolate/formoterol, rate ratio 0.76 (95% CI 0.69 to 0.83, p<0.001); against budesonide/formoterol, 0.87 (0.79 to 0.95, p=0.003). Confirmed pneumonia occurred in 3.5 to 4.5% of the steroid-containing arms versus 2.3% with glycopyrrolate/formoterol. |
| Secondary endpoints | Lung function, symptoms, mortality, pneumonia |
Triple therapy with twice-daily budesonide (at either the 160-microg or 320-microg dose), glycopyrrolate, and formoterol resulted in a lower rate of moderate or severe COPD exacerbations than glycopyrrolate-formoterol or budesonide-formoterol.
The trial authors, in the published abstract
The cleaner of the two big triple-therapy trials, because it did not withdraw inhaled steroids at randomisation the way IMPACT did. That the 160 microg dose matched the 320 microg dose is the practical finding: the exacerbation benefit does not require the higher steroid burden.
Rabe KF, Martinez FJ, Ferguson GT, et al. Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very-Severe COPD. N Engl J Med 2020 Jul 2;383(1):35-48.