Rationale and Design of the Roflumilast or Azithromycin to Prevent COPD Exacerbations Clinical Trial.
RATIONALE: Rationale: Chronic obstructive pulmonary disease (COPD) is a leading cause of hospitalization and death, particularly among patients with chronic bronchitis and frequent exacerbations. Results of placebo-controlled clinical trials indicate that treatment escalation with either long-term oral roflumilast or azithromycin can reduce COPD exacerbations. However, head-to-head comparative data from clinical trials are lacking, so the relative harms and benefits of these treatments are unclear. OBJECTIVE: The RofLumilast or Azithromycin to preveNt COPD Exacerbations (RELIANCE) study is an investigator-initiated, multicenter, randomized, pragmatic clinical trial embedded in clinical practice to evaluate the effectiveness of treatment escalation with long-term azithromycin versus roflumilast in patients with COPD and chronic bronchitis. METHODS/DESIGN: We solicited preferences from patients, clinicians, and other stakeholders during the design and implementation phases of the study, including feedback that informed modifications related to the COVID-19 pandemic. Eligibility criteria did not require assessments outside of clinical practice, with exclusions principally for safety. The composite endpoint of first all-cause hospitalization or death served as the primary outcome. Enrollment was initially through university-affiliated clinical centers but was subsequently expanded to recruit patients in community-based practices who might not otherwise participate in research. We employed human-centered design principles to improve the usability of study activities from the perspective of participants, study staff, and treating clinicians. FINAL DESIGN: The final study design offered the option for patients with COPD and chronic bronchitis at high-risk of hospitalization or death to be remotely consented, prescribed a medication according to the randomized treatment allocation, and complete virtual follow-up study visits in a decentralized clinical trial.
