Table 5.
Severe Exacerbations and All-Cause Mortality in the TRIBUTE, ETHOS, and IMPACT Trials
| TRIBUTE23 | ETHOS24 | IMPACT22,89 | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Study arms | BDP/FM/GLY BID (N=764) | IND/GLY QD (N=768) | BUD (320)/GLY/FM BID (N=2137) | BUD (160)/GLY/FM BID (N=2121) | FM/GLY BID (N=2120) | BUD/FM BID (N=2131) | FF/UMEC/VI QD (N=4151) | FF/VI QD (N=4134) | UMEC/VI QD (N=2070) |
| On-treatment severe exacerbations | |||||||||
| Rate, per year | 0.07 | 0.09 | 0.13 | 0.14 | 0.15 | 0.16 | 0.13 | 0.15 | 0.19 |
| Rate ratio (95% CI), SITT vs dual therapy | – | 0.787 (0.551, 1.125), P=0.189 | – | – | BUD 320 µg SITT: 0.84 (0.69, 1.03), P=0.09 BUD 160 µg SITT: 0.88 (0.72, 1.08), P-value not reported |
BUD 320 µg SITT: 0.80 (0.66, 0.97), P=0.02 BUD 160 µg SITT: 0.83 (0.69, 1.01), P-value not reported |
– | 0.87 (0.76, 1.01), P=0.06 | 0.66 (0.56, 0.78), P<0.001 |
| On-/off-treatment death from any causea | |||||||||
| Deaths, n (%) | 16 (2.09%)b | 21 (2.73%)b | 28 (1.31%) | 39 (1.84%) | 49 (2.31%) | 34 (1.60%) | 89 (2.14%) | 97 (2.35%) | 60 (2.90%) |
| Relative risk reduction, SITT vs dual therapy: HR (95% CI) | – | NR | – | – | BUD 320 µg SITT: 0.54 (0.34, 0.87)c BUD 160 µg SITT: 0.79 (0.52, 1.20) |
BUD 320 µg SITT: 0.78 (0.47, 1.30) BUD 160 µg SITT: 1.13 (0.72, 1.80) |
– | 0.90 (0.67, 1.20), P=0.458 | 0.71 (0.51, 0.99), P=0.043 |
| Absolute risk difference, SITT vs dual therapy | – | 0.64%b | – | – | BUD 320 µg SITT: 1.00% BUD 160 µg SITT: 0.47% |
BUD 320 µg SITT: 0.29% BUD 160 µg SITT: −0.24% |
– | 0.21% | 0.76% |
Notes: Data are over 52 weeks in the ITT population, unless otherwise indicated. aETHOS: analysis performed with the use of a treatment policy estimand, which included all observed data regardless of whether patients continued to receive their assigned treatment,24 IMPACT: on- and off-treatment deaths included all observed data regardless of whether patients continued to receive their assigned treatment and are those which occurred between study treatment start date and 7 days after study treatment stop date (inclusive) for study treatment completers or up to the projected Week 52 date + 7 days for patients who prematurely discontinued study treatment;89 bAEs leading to a fatal outcome (safety population); cno statistical inferences can be made due to hierarchy broken on severe exacerbations.
Abbreviations: BDP, beclometasone dipropionate; BUD, budesonide; CI, confidence interval; FF, fluticasone furoate: FM, formoterol; GLY, glycopyrronium; HR, hazard ratio; IND, indacaterol; NR, not reported; SITT, single-inhaler triple therapy; UMEC, umeclidinium; VI, vilanterol.