Efficacy of aclidinium/formoterol fixed-dose combination versus salmeterol/fluticasone in COPD
Bibliographic record
Abstract
Background: Aclidinium bromide/formoterol fumarate fixed-dose combination (FDC) twice daily (BID) is licensed in Europe for COPD treatment. Aim: To evaluate the efficacy of aclidinium/formoterol vs. salmeterol/fluticasone propionate FDC (SAL/FLU) in patients with COPD. Methods: A randomised, double-blind, Phase IIIb, 24-week study in patients with COPD Assessment Test (CAT) score ≥10 compared aclidinium/formoterol 400/12 µg BID via Genuair ® with SAL/FLU 50/500 µg BID via Accuhaler ® (NCT01908140). Endpoints were peak FEV 1 (primary), Transition Dyspnoea Index (TDI; secondary), CAT, device preference and exacerbations. Non-inferiority of aclidinium/formoterol vs. SAL/FLU was tested for peak FEV 1 and TDI. Superiority in peak FEV 1 was also analysed. Adverse events (AEs) were monitored throughout. Results: 933 patients were randomised: mean age 63.4 years; 65.1% male; mean post bronchodilator FEV 1 1.48 L (53.2% predicted); mean CAT score 18.5. 788 patients (84.5%) completed the study. Aclidinium/formoterol achieved greater peak FEV 1 vs. SAL/FLU from Day 1 to Week 24 (p < 0.0001; Table). Improvements in TDI, CAT and exacerbations were similar in both groups (Table). More patients preferred Genuair (51.9%) than Accuhaler (18.5%, p < 0.0001). The incidence of AEs, and AEs leading to study discontinuation was similar across groups. The most common AEs were COPD exacerbations (17.5%), headache (6.4%) and nasopharyngitis (5.8%). Conclusion: Superiority in peak FEV 1 and non-inferiority in TDI were demonstrated for aclidinium/formoterol FDC vs. SAL/FLU in patients with stable COPD. Improvements in quality of life and exacerbations were similar in both groups. More patients preferred Genuair to Accuhaler. Both treatments were well tolerated. Tab. 1: Efficacy of aclidinium/formoterol FDC vs. salmeterol/fluticasone FDC Aclidinium/formoterol 400/12 µg BID n = 468 Salmeterol/fluticasone 50/500 µg BID n = 463 Peak FEVi at baseline, L, mean (95% Cl) a 1.39 (1.34, 1.44) 1.38 (1.33, 1.43) PeakFEVi at Week 24, L, mean (95% Cl) b 1.66 (1.63, 1.68)"' 1.56 (1.54, 1.58) TDI focal score at Week 24, units, mean (95% Cl) b,c 1.88 (1.54, 2.21) 1.88 (1.54, 2.22) CAT total score at Week 24, units, mean (95% Cl) b 15.81 (15.23, 16.40) 16.11 (15.53, 16.70) Patients with ≥1 HCRU- defined exacerbation during study, % 15.8 16.6 Patients with ≥1 EXACT- identified exacerbation during study, % 37.8 39.5 Efficacy data were analysed in the intent-to-treat population with the exception of TDI focal score, which was analysed in the per-protocol population (non-inferiority analyses) 66 (14.1%) patients in the aclidinium/formoterol group and 79 (17.0%) in the salmeterol/fluticasone group did not complete the study Two patients randomised to aclidinium/formoterol 400/12 µg BID received salmeterol/fluticasone 50/500 µg BID; one patient randomised to salmeterol/fluticasone 50/500 µg BID received aclidinium/formoterol 400/12 µg BID. Efficacy data for these patients were analysed according to randomisation, safety data were analysed according to received treatment. a Absolute value b Data reported as least squares means c Per-protocol population: aclidinium/formoterol 400/12 µg BID n = 423; salmeterol/fluticasone 50/500 µg BID n = 414 ***p < 0.0001 vs. salmeterol/fluticasone 95% CI, 95% confidence interval; BID, twice daily; CAT, COPD Assessment Test; EXACT, EXAcerbations of Chronic pulmonary disease Tool; FEV 1 , forced expiratory volume in 1 second; HCRU, healthcare resource utilisation; TDI, Transition Dyspnoea Index Funding This study was funded by Almirall S.A., Barcelona, Spain. Medical writing support, funded by AstraZeneca PLC, Barcelona, Spain, was provided by Richard Knight of Complete Medical Communications.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".