A comparative effectiveness trial: Roflumilast vs. Azithromycin for severe COPD
RELIANCE will compare the relative benefits and harms of the 2015 ACCP/CTS guidelines and 2019 GOLD guidelines -recommended treatment intensification options in patients with severe COPD associated with chronic bronchitis. The clinical trial is designed to inform your efforts to reduce avoidable re-hospitalizations and death in patients recently discharged from the hospital following a COPD exacerbation.
Reducing clinical uncertainty
Through a set of online surveys, we contacted practicing physicians to learn about their use of Roflumilast and Azithromycin. Of 43 practicing pulmonologists who responded, 91% used Azithromycin or Roflumilast. Altogether, about 60% believe that Roflumilast and Azithromycin are equally effective or they don’t know which is better.
Which drug is better for whom?
Results of RCTs indicate that either Azithromycin or Roflumilast is better than placebo to reduce COPD exacerbations. What we don’t know is which is better for which type of patient.
The RELIANCE trial is designed to examine the relative harms and benefits of treatment intensification with Roflumilast or Azithromycin in patients with COPD who are at high risk for hospitalization or death and are already on inhaled maintenance therapy. We will compare Roflumilast and Azithromycin separately in current and past smokers (assessed at enrollment). Both intention-to-treat (primary) and per-protocol analyses will also be performed. The primary outcome is all-cause rehospitalization or death.
The results of the RELIANCE study are intended to inform decision-making regarding the treatment of choice in high-risk patients with COPD as well as efforts to promote antibiotic stewardship.
Fitting COPD care to real world patient and clinician practices
RELIANCE will assess the combined effects of “real-world” patient and clinician practices plus pharmacologic efficacy in individual patients. Because RELIANCE is an effectiveness trial, it is inclusive of adverse effects, out-of-pocket costs of medications, co-morbid conditions and other factors contribute to patient/clinician practices, including dosing, dose-titrations, adherence and treatment discontinuations, cross-overs, and use of co-therapies.
Medications will not be provided to patients. Clinicians will ask the patients to fill the prescription as per usual practice.
Clinicians retain the flexibility to select alternate regimens (e.g., starting at a lower dose and titrating up), discontinuing therapy, crossing-over to the alternate treatment, or combining both treatments at any time, as clinically indicated.
No additional visits are required for RELIANCE participants.
To support clinicians participating in RELIANCE, we address two real-world, pragmatic issues—cost of medications and side effects—through the design of patient support materials. These materials are optimized to support decision-making and communication between clinicians and patients. Potential side effects of both azithromycin and roflumilast are summarized here:
Azithromycin may cause diarrhea, nausea, abdominal pain, or vomiting; it may also increase the risk of antibiotic resistance or cardiac dysrhythmias.
Roflumilast can cause diarrhea, weight loss, nausea, headache, back pain, influenza, insomnia, dizziness, and decreased appetite.
Patient facing materials on medication cost, harms and benefits: