A trial of beclomethasone/formoterol in COPD using EXACT-PRO to measure exacerbations

Abstract

Combination inhalers containing corticosteroids and long-acting b-agonists are used to reduce exacerbation rates in patients with severe chronic obstructive pulmonary disease (COPD).The FORWARD (Foster 48-week Trial to Reduce Exacerbations in COPD) clinical trial in severe COPD patients is a comparison of extrafine beclomethasone dipropionate and formoterol in a combination inhaler with extrafine formoterol; the co-primary end-points are exacerbation rates over 48 weeks and improvement in forced expiratory volume in 1 s over 12 weeks. The traditional physician diagnosis of exacerbations is a co-primary outcome, and the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) means of collecting patient-reported outcome data are also being used to enhance the detection of exacerbation events. EXACT data are being collected using a novel application of a digital platform technology.FORWARD is therefore expected to provide information on the ability of EXACT to detect and measure exacerbations in a large clinical trial setting. The study design of FORWARD is described in this article.

Detection and severity grading of COPD exacerbations using the exacerbations of chronic pulmonary disease tool (EXACT)

“…Nonetheless, despite these caveats, it remains a concern that only approximately one-third of HCU exacerbations within this study fulfilled the criteria for an EXACT event. The strength of the relationship between EXACT events and HCU exacerbations in our study is consistent with preliminary data from the FORWARD (Foster 48-week Trial to Reduce Exacerbations in COPD) trial, which used the traditional physician diagnosis of exacerbations as a co-primary outcome, and the EXACT to enhance exacerbation detection, and also found marked inconsistencies between EXACT events and HCU exacerbations [21,22].…”

“…It should be noted that patients in the London COPD cohort are instructed to report increased respiratory symptoms as recorded in their diary to ensure prompt assessment and therapy as required, and were not instructed to report based upon EXACT responses. Some studies have attempted to use EXACT scores to enhance reporting of exacerbations by remotely monitoring EXACT scores in real time and using worsening scores to generate an alert regarding a possible exacerbation [21]; however, this was not the case in our study.…”

Fluticasone propionate/formoterol for COPD management: a randomized controlled trial

“…However, it is also relevant that other trials of ICS/LABA combinations have failed to show exacerbation risk reduction versus LABA monotherapy 25–29. In the light of earlier unsuccessful ICS/LABA trials, several steps were taken to mitigate such an outcome: patients had severe airways obstruction; documentation confirming an exacerbation within the past 12 months was required for enrolment; “recent” exacerbations did not preclude enrolment other than if occurring during the run-in or at screening; a tiotropium run-in was employed to facilitate retention of as many patients as possible during the pre-randomization phase (<6% of subjects discontinued during the run-in); the study was of 12 months duration, thereby mitigating for seasonal variations in exacerbation rates;30 and the EXACT PRO was used to encourage detection of a greater proportion of unreported exacerbation events, as per the recent FORWARD study 8,31. Furthermore, the pooled exacerbation rate was monitored on an ongoing basis and additional subjects were enrolled via a protocol amendment to preserve study power when it became apparent that the observed overall exacerbation rate was lower than initially predicted 20…”

Co-morbidity of bronchial asthma and chronic obstructive pulmonary disease

“…сравнительное исследование Фостера и салметерола / флутиказона пропионата доказало способность Фостера умень шать гиперинфляцию и одышку у пациентов с ХОБЛ, при этом статистически достоверное сокращение ос таточного объема легких было зарегистрировано только в группе Фостера [68]. Таким образом, ис пользование ЭМД аэрозолей является одним из наиболее перспективных путей повышения эффек тивности ГКС терапии и исследования в этой облас ти активно продолжаются [69].…”