Respiratory Trials·org

COPD · Triple versus dual therapy

TRIBUTE

Extrafine triple therapy versus dual bronchodilation in COPD

TRIBUTE trial design and results
Design Double-blind, double-dummy, parallel-group RCT at 187 sites in 17 countries
Treatment Extrafine beclometasone 87 microg / formoterol 5 microg / glycopyrronium 9 microg, two inhalations twice daily
Control Indacaterol 85 microg / glycopyrronium 43 microg once daily
Population 1532 patients with symptomatic COPD, severe or very severe airflow limitation, and an exacerbation in the previous year
Follow-up 52 weeks
Primary endpoint Rate of moderate-to-severe COPD exacerbations
Result 0.50 per patient-year (95% CI 0.45 to 0.57) with triple therapy versus 0.59 (0.53 to 0.67) with indacaterol/glycopyrronium — rate ratio 0.848 (0.723 to 0.995, p=0.043). Pneumonia occurred in 28 of 764 (4%) versus 27 of 768 (4%).
Secondary endpoints Lung function, symptoms, adverse events including pneumonia

In patients with symptomatic COPD, severe or very severe airflow limitation, and an exacerbation history despite maintenance therapy, extrafine BDP/FF/G significantly reduced the rate of moderate-to-severe exacerbations compared with IND/GLY, without increasing the risk of pneumonia.

The trial authors, in the published abstract

How it has aged

A smaller and more marginal result than IMPACT or ETHOS — the confidence interval very nearly crosses one. Its distinctive finding is the absence of a pneumonia signal, which has been attributed to the extrafine formulation and the lower steroid dose, though the trial was not powered to settle that.

Publications

Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial

Papi A, Vestbo J, Fabbri L, et al. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial. Lancet 2018 Mar 17;391(10125):1076-1084.

  • 15% lower moderate-to-severe exacerbation rate than indacaterol/glycopyrronium
  • No increase in pneumonia with the inhaled steroid-containing arm