Roflumilast or Azithromycin to Prevent COPD Exacerbations Trial
RELIANCE
2 other identifiers
interventional
1,032
1 country
28
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Feb 2020
Longer than P75 for phase_3
28 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 23, 2019
CompletedFirst Posted
Study publicly available on registry
August 28, 2019
CompletedStudy Start
First participant enrolled
February 11, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2026
CompletedJuly 8, 2026
July 1, 2026
6.1 years
August 23, 2019
July 6, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Time to first all-cause hospitalization or all-cause death
Composite time-to-event outcome defined as time from randomization to the first occurrence of all-cause hospitalization or all-cause death.
Baseline to study exit (up to 72 months)
Secondary Outcomes (21)
Time to first moderate COPD exacerbation, all-cause hospitalization, or all-cause death
Baseline to study exit (up to 72 months)
Time to first moderate COPD exacerbation
Baseline to study exit (up to 72 months)
Time to first all-cause hospitalization
Baseline to study exit (up to 72 months)
Time to all-cause death
Baseline to study exit (up to 72 months)
Change in physical function as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS) scale
Measured at study registration, 3 months, and 6 months
- +16 more secondary outcomes
Study Arms (2)
Roflumilast arm
ACTIVE COMPARATORParticipants 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
ACTIVE COMPARATORParticipants will receive prescription for Azithromycin (250 mg/day, or 500 mg three times per week, or alternate regimen) x 6 to 72 months
Interventions
Prescription for Roflumilast (250 mcg/day x 4 weeks, then 500 mcg/day or alternate regimen) x 6 to 72 months
Prescription for Azithromycin (250 mg/day, or 500 mg three times per week, or alternate regimen) x 6 to 72 months
Eligibility Criteria
You may qualify if:
- 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 by treating clinician of severe COPD and associated chronic bronchitis
- Hospitalized with a diagnosis of COPD exacerbation or respiratory complications due to Coronavirus Disease 2019 (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(note patients prescribed or using Short-Acting Beta-Agonist (SABA), Short-Acting Muscarinic Antagonist (SAMA), or SABA/SAMA on a scheduled basis (e.g., every 6 hours) are eligible since the patient is receiving functional controller therapy)
- English or Spanish speaking
- Willing and able to provide a contact telephone number
You may not qualify if:
- Unable or declines to provide informed consent
- Declines to provide social security number, health insurance claims number or Tax Payer ID (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
- 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
- The clinicians will be provided the FDA-approved prescribing information for roflumilast and azithromycin. The prescribing information includes a list of warnings and precautions that identifies the potential for adverse effects and is intended to support clinical decision-making that takes into account the risks and benefits of roflumilast and azithromycin for each patient.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Illinois at Chicagocollaborator
- Johns Hopkins Universitylead
- Patient-Centered Outcomes Research Institutecollaborator
Study Sites (28)
University of Alabama
Birmingham, Alabama, 35233, United States
University of Arizona
Tucson, Arizona, 85734, United States
University of California, Davis Health
Sacramento, California, 95817, United States
Northwestern
Chicago, Illinois, 60611, United States
University of Illinois Chicago
Chicago, Illinois, 60612, United States
NorthShore Hospital
Glenview, Illinois, 60026, United States
University of Iowa
Iowa City, Iowa, 52242, United States
University of Kansas
Kansas City, Kansas, 66160, United States
Ochsner Medical Center
New Orleans, Louisiana, 70121, United States
Johns Hopkins University
Baltimore, Maryland, 21224, United States
Baystate Health
Springfield, Massachusetts, 01199, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Henry Ford Health System
Detroit, Michigan, 48202, United States
University of Missouri, Kansas City
Kansas City, Missouri, 64108, United States
Lenox Hill/Northern Westchester Hospital (Northwell Health)
Mount Kisco, New York, 10549, United States
Mount Sinai
New York, New York, 10029, United States
University of North Carolina, School of Medicine
Chapel Hill, North Carolina, 27599, United States
Duke
Durham, North Carolina, 27705, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Ohio State University
Columbus, Ohio, 43210, United States
Kaiser Permanente
Portland, Oregon, 97227, United States
Temple University Hospital
Philadelphia, Pennsylvania, 19140, United States
University of Pittsburg Medical Center
Pittsburgh, Pennsylvania, 15213, United States
Baylor Scott & White (BSW) Health-North
Dallas, Texas, 75246, United States
Houston Methodist Hospital
Houston, Texas, 77030, United States
University of Vermont
Burlington, Vermont, 05401, United States
Providence Health and Services
Spokane, Washington, 99204, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jerry Krishnan, MD, PhD
University of Illinois at Chicago
- PRINCIPAL INVESTIGATOR
Robert Wise, MD
Johns Hopkins School of Medicine
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Masking Details
- Treatment assignments will be concealed prior to randomization. Once a patient is assigned to receive a treatment, the clinician, Site Coordinator and patient will not be masked. i.e., will know the treatment assignment
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 23, 2019
First Posted
August 28, 2019
Study Start
February 11, 2020
Primary Completion
March 1, 2026
Study Completion
March 1, 2026
Last Updated
July 8, 2026
Record last verified: 2026-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
- Time Frame
- The start date will be after 5/1/2027. Data and document transfer and curation is scheduled to be completed by 5/1/2027 after which PCORI (study funder) will determine the start date based on the publication status of the primary results manuscript or Final Research Report. There is no end date.
- Access Criteria
- Investigators submit requests via ICPSR web-based data access request system. Requests include investigator, research staff and institution information, proposed research purpose/description, specific files needed, signed confidentiality pledges, data security plan, IRB approval or exemption for proposed research, assurance that data use is to develop/contribute to generalizable knowledge, and justification research project can be achieved using the requested data. Requests are evaluated by an independent committee. If approved, ICSPR and Investigator enter into a Restricted Data Use Agreement for Restricted Data in the Virtual Data Enclave (VDE), which describes investigator, research staff and institution obligations including data use only for described project, compliance with data security plan, access limited to persons identified in agreement, and no attempts to identify private persons are permitted. Data is made available via the VDE, a secure remote-access workspace.
The Inter-University Consortium for Political and Social Research (ICPSR) at the University of Michigan will provide data archiving and dissemination services for RELIANCE. After entering into a Restricted-Use Data Contributor Agreement with ICPSR, the RELIANCE Data Coordinating Center (DCC) will prepare and transfer restricted-use files for the analyzable data set and supporting document to ICPSR. The data files will be prepared per Safe Harbor methods for compliance with the HIPAA Privacy Rule. IPD includes: demographic data, BMI, type of insurance, smoking history, COPD treatments; lung function measurements, comorbidities, use of study assigned treatment, responses to quality of life questions, adverse events, symptoms and information on hospitalizations and death.