Roflumilast or Azithromycin to Prevent COPD Exacerbations (RELIANCE)

Chronic Bronchitis Clinical Trial

— RELIANCE  

Official title:

Roflumilast or Azithromycin to Prevent COPD Exacerbations (RELIANCE)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04069312
• Other study ID #: IRB00179281
• Status: Recruiting
• Phase: Phase 3
• Start date: February 11, 2020
• Est. completion date: February 2027

Study information

• Verified date: March 2024
• Source: Johns Hopkins University
• Contact: Jill Meinert
• Phone: 4109558197
• Email: Jmeiner1[@]jhu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 1,200 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 information / eligibility

• Status: Recruiting
• Enrollment: 1200
• Est. completion date: February 2027
• Est. primary completion date: February 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Bronchitis
• Bronchitis, Chronic
• Chronic Bronchitis
• Chronic Obstructive Pulmonary Disease Severe
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Roflumilast
Prescription for Roflumilast (250 mcg/day x 4 weeks, then 500 mcg/day or alternate regimen) x 6 to 72 months
• Azithromycin
Prescription for Azithromycin (250 mg/day, or 500 mg three times per week, or alternate regimen) x 6 to 72 months

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Alabama	Birmingham	Alabama
United States	University of Vermont	Burlington	Vermont
United States	University of North Carolina, School of Medicine	Chapel Hill	North Carolina
United States	Northwestern	Chicago	Illinois
United States	University of Illinois, Chicago	Chicago	Illinois
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Baylor Scott & White (BSW) Health-North	Dallas	Texas
United States	Denver Health	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke	Durham	North Carolina
United States	NorthShore Hospital	Glenview	Illinois
United States	University of Iowa	Iowa City	Iowa
United States	University of Missouri, Kansas City	Kansas City	Missouri
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	Lenox Hill Hospital/Northwell Health	New York	New York
United States	Mount Sinai	New York	New York
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	University of Pittsburg Medical Center	Pittsburgh	Pennsylvania
United States	Kaiser Permanente	Portland	Oregon
United States	University of California, Davis Health	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Providence Health and Services	Spokane	Washington
United States	Baystate Health	Springfield	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	Patient-Centered Outcomes Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of All-cause hospitalizations	All-cause hospitalizations	Up to 72 months
Primary	Number of All-cause deaths	All-cause deaths	Up to 72 months
Secondary	Number of All-cause individual events	All-cause individual events	Up to 72 months
Secondary	Change in physical function as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS) scale	Based on the scoring scale; a score of 5 is the most favorable and a score of 1 is least favorable.	Baseline, 3 months, 6 months and every 6 months up to 72 months
Secondary	Change in problems with sleep as assessed by the PROMIS scale	1 is least favorable and 5 is most favorable	Baseline, 3 months, 6 months and every 6 months up to 72 months
Secondary	Change in fatigue as assessed by the PROMIS scale	0 is most favorable and 4 and least favorable	Baseline, 3 months, 6 months and every 6 months up to 72 months
Secondary	Change in anxiety as assessed by the PROMIS scale	Score of 1 is most favorable and 5 is least favorable	Baseline, 3 months, 6 months and every 6 months up to 36 months
Secondary	Change in depression as assessed by the PROMIS scale	1 is most favorable and 5 is least favorable	Baseline, 3 months, 6 months and every 6 months up to 72 months
Secondary	Number of Adverse Events	Adverse events	Up to 72 months
Secondary	Medication Adherence as assessed by patient self-report	Medication Adherence will be assessed by self-report via Call Center or Patient Portal; Medicare claims data in a subset.	Up to 72 months
Secondary	Number of participants that switch to alternate study medication	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	Up to 72 months
Secondary	Out of pocket cost for study medication	Out of pocket costs for roflumilast of azithromycin by self-report via Call Center or Patient Portal	Up to 72 months
Secondary	Change in weight	Weight in lbs	3 and 6 months
Secondary	Number of participants that discontinued medication	This will be collected by self-report via Call Center or Patient Portal; query of clinic staff; Medicare claims data in a subset	Up to 72 months