Roflumilast or Azithromycin to Prevent COPD Exacerbations (RELIANCE)
- Conditions
- Chronic Obstructive Pulmonary Disease SevereChronic Bronchitis
- Interventions
- Registration Number
- NCT04069312
- Lead Sponsor
- Johns Hopkins University
- Brief Summary
A multi-center, randomized, 72-month, parallel- group, non-inferiority, phase III study to compare the effectiveness of roflumilast (Daliresp, 500 mcg quaque die (QD) or alternate regimen) therapy versus azithromycin (250 mg QD, 500 mg QD three times per week, or alternate regimen) to prevent hospitalization or death in a patients at high risk for COPD exacerbations.
- Detailed Description
RELIANCE is a U.S.-based pragmatic clinical trial funded by the Patient-Centered Outcomes Research Institute (PCORI) to compare long-term use of roflumilast vs. azithromycin in up to 1,250 patients. It is intended to support hospital efforts to reduce the risk of all-cause hospitalization and reduce pre-mature deaths in individuals with chronic obstructive pulmonary disease (COPD) who have been hospitalized in the prior year for a COPD exacerbation. The COPD Patient Powered Research Network (PPRN) and affiliated investigators will conduct the trial in sites in the U.S.
Both roflumilast and azithromycin have been shown to reduce the risk of COPD exacerbations compared to placebo. However, there has not been a head-to-head comparison of the two medications. So, the relative harms and benefits of the two medications are unknown. Eligible patients will be randomized (1:1) to receive either a prescription for roflumilast or a prescription for azithromycin, and will be followed for at least 6 and up to 72 months. The primary endpoint is the combined outcome of all-cause hospitalization or death; the secondary endpoints include premature treatment discontinuation, patient-reported adverse effects, and physical, social, and emotional health. Patients will be enrolled at participating clinical sites and follow up data will be collected via an online patient portal or via a call center. Baseline and outcome data will also be collected from site medical records and administrative/claims databases.
Pragmatic, non-inferiority trial using an intention-to-treat analysis to evaluate whether daily azithromycin is non-inferior to daily roflumilast in patients at high risk of COPD exacerbations. The investigators will randomize individual patients to receive prescriptions for roflumilast or azithromycin (1:1 ratio), stratified by site and current smoking status (yes/no).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1250
- Patient and treating clinician considering treatment intensification with roflumilast or azithromycin to reduce the risk of COPD exacerbations
- Age ≥ 40 years
- Current or past smoker of at least 10 pack-years
- Diagnosis of severe COPD and associated chronic bronchitis
- Hospitalized with a diagnosis of COPD exacerbation or respiratory complications due to COVID 19 in the past 12 months
- Current medications include inhaled Long Acting Muscarinic Antagonist (LAMA), Long Acting Beta Agonist (LABA) /LAMA, or Inhaled Corticosteroids (ICS) /LABA
- English or Spanish speaking
- Unable or declines to provide informed consent;
- Declines to provide social security number or health insurance claims number (as applicable)
- History of intolerance to azithromycin or roflumilast that the patient or patient's treating clinician considers sufficiently serious to avoid either treatment option;
- Current treatment with long-term (more than 30 days) roflumilast or azithromycin (previous treatment with 1 or more doses of azithromycin or roflumilast is not an exclusion criterion, as long as the patient and clinician are seeking treatment intensification options and would be willing to use azithromycin or roflumilast, as per randomized treatment assignment.)
- Known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide antibiotic;
- History of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin
- Moderate to severe liver impairment (Child-Pugh B or C)
- Current pregnancy
- Any other clinician-determined exclusion as per the clinician's clinical practice
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Roflumilast arm Roflumilast Participants will receive prescription for Roflumilast (250 mcg/day x 4 weeks, then 500 mcg/day or alternate regimen) x 6 to 72 months Azithromycin arm Azithromycin Participants will receive prescription for Azithromycin (250 mg/day, or 500 mg three times per week, or alternate regimen) x 6 to 72 months
- Primary Outcome Measures
Name Time Method Number of All-cause hospitalizations Up to 72 months All-cause hospitalizations
Number of All-cause deaths Up to 72 months All-cause deaths
- Secondary Outcome Measures
Name Time Method Change in physical function as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS) scale Baseline, 3 months, 6 months and every 6 months up to 72 months Based on the scoring scale; a score of 5 is the most favorable and a score of 1 is least favorable.
Change in fatigue as assessed by the PROMIS scale Baseline, 3 months, 6 months and every 6 months up to 72 months 0 is most favorable and 4 and least favorable
Change in depression as assessed by the PROMIS scale Baseline, 3 months, 6 months and every 6 months up to 72 months 1 is most favorable and 5 is least favorable
Number of participants that switch to alternate study medication Up to 72 months Patient will be assigned either azithromycin or roflumilast at randomization. We will assess any switch to either roflumilast from azithromycin or azithromycin from roflumilast by self-report via Call Center or Patient Portal, query of clinic staff; Medicare claims data in a subset
Number of participants that discontinued medication Up to 72 months This will be collected by self-report via Call Center or Patient Portal; query of clinic staff; Medicare claims data in a subset
Change in problems with sleep as assessed by the PROMIS scale Baseline, 3 months, 6 months and every 6 months up to 72 months 1 is least favorable and 5 is most favorable
Change in anxiety as assessed by the PROMIS scale Baseline, 3 months, 6 months and every 6 months up to 36 months Score of 1 is most favorable and 5 is least favorable
Number of All-cause individual events Up to 72 months All-cause individual events
Number of Adverse Events Up to 72 months Adverse events
Medication Adherence as assessed by patient self-report Up to 72 months Medication Adherence will be assessed by self-report via Call Center or Patient Portal; Medicare claims data in a subset.
Out of pocket cost for study medication Up to 72 months Out of pocket costs for roflumilast of azithromycin by self-report via Call Center or Patient Portal
Change in weight 3 and 6 months Weight in lbs
Trial Locations
- Locations (27)
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
Mount Sinai
🇺🇸New York, New York, United States
Lenox Hill Hospital/Northwell Health
🇺🇸New York, New York, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
University of Missouri, Kansas City
🇺🇸Kansas City, Missouri, United States
Baystate Health
🇺🇸Springfield, Massachusetts, United States
Duke
🇺🇸Durham, North Carolina, United States
Kaiser Permanente
🇺🇸Portland, Oregon, United States
Providence Health and Services
🇺🇸Spokane, Washington, United States
University of Vermont
🇺🇸Burlington, Vermont, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
University of Alabama
🇺🇸Birmingham, Alabama, United States
Northwestern
🇺🇸Chicago, Illinois, United States
University of California, Davis Health
🇺🇸Sacramento, California, United States
University of Illinois, Chicago
🇺🇸Chicago, Illinois, United States
NorthShore Hospital
🇺🇸Glenview, Illinois, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
University of North Carolina, School of Medicine
🇺🇸Chapel Hill, North Carolina, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburg Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
University of Kansas
🇺🇸Kansas City, Kansas, United States
Ochsner Medical Center
🇺🇸New Orleans, Louisiana, United States
Baylor Scott & White (BSW) Health-North
🇺🇸Dallas, Texas, United States