One-year safety and efficacy study of arformoterol tartrate in patients with moderate to severe COPD

Abstract

Background: Arformoterol tartrate (arformoterol, 15 μg bid) is a nebulized long-acting β2-agonist approved for maintenance treatment of COPD.

Methods: This was a multicenter, double-blind, randomized, placebo-controlled study. Patients (aged ≥ 40 years with baseline FEV1 ≤ 65% predicted, FEV1 > 0.50 L, FEV1/FVC ≤ 70%, and ≥ 15 pack-year smoking history) received arformoterol (n = 420) or placebo (n = 421) for 1 year. The primary assessment was time from randomization to respiratory death or first COPD exacerbation-related hospitalization.

Results: Among 841 patients randomized, 103 had ≥ 1 primary event (9.5% vs 15.0%, for arformoterol vs placebo, respectively). Patients who discontinued treatment for any reason (39.3% vs 49.9%, for arformoterol vs placebo, respectively) were followed for up to 1 year postrandomization to assess for primary events. Fewer patients receiving arformoterol than placebo experienced COPD exacerbation-related hospitalizations (9.0% vs 14.3%, respectively). Twelve patients (2.9%) receiving arformoterol and 10 patients (2.4%) receiving placebo died during the study. Risk for first respiratory serious adverse event was 50% lower with arformoterol than placebo (P = .003). Numerically more patients on arformoterol (13; 3.1%) than placebo (10; 2.4%) experienced cardiac serious adverse events; however, time-to-first cardiac serious adverse event was not significantly different. Improvements in trough FEV1 and FVC were greater with arformoterol (least-squares mean change from baseline vs placebo: 0.051 L, P = .030 and 0.075 L, P = .018, respectively). Significant improvements in quality of life (overall St. George's Hospital Respiratory Questionnaire and Clinical COPD Questionnaire) were observed with arformoterol vs placebo (P < .05).

Conclusions: Arformoterol demonstrated an approximately 40% lower risk of respiratory death or COPD exacerbation-related hospitalization over 1 year vs placebo. Arformoterol was well-tolerated and improved lung function vs placebo.

Trial registry: ClinicalTrials.gov; No.: NCT00909779; URL: www.clinicaltrials.gov.

Figures

Figure 1 –

Consolidated Standards of Reporting Trials (CONSORT) diagram. ITT = intent to treat.

Figure 2 –

Study design. ARF15BID = arformoterol tartrate 15 μg bid.

Figure 3 –

Kaplan-Meier plot of the cumulative probability of events for time to respiratory death or first COPD exacerbation-related hospitalization (ITT population). See Figure 1 and 2 legends for expansion of abbreviations.

Figure 4 –

Primary and sensitivity analyses for time-to-first-event analysis: hazard ratio and 90% repeated CI (ITT population). Hazard ratios are indicated by ×; ● represents the bounds of the CIs. IPD = important protocol deviation. See Figure 1 and 2 legends for expansion of other abbreviations.