Roflumilast or Azithromycin to Prevent COPD Exacerbations (RELIANCE)

NCT04069312 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: IRB00179281
• Study Type: interventional
• Target: 1,032
• Locations: 1 country
• Sites: 29

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.

Conditions

Chronic Obstructive Pulmonary Disease Severe; Chronic Bronchitis

Keywords

Chronic Obstructive Pulmonary Disease; Chronic Bronchitis; COPD; Roflumilast; Daliresp; Azithromycin

Outcome Measures

Primary Outcomes (2)

• Number of All-cause hospitalizations

  All-cause hospitalizations

  Up to 72 months

• Number of All-cause deaths

  All-cause deaths

  Up to 72 months

Secondary Outcomes (12)

• Number of All-cause individual events

  Up to 72 months

• 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

• Change in problems with sleep as assessed by the PROMIS scale

  Baseline, 3 months, 6 months and every 6 months up to 72 months

• Change in fatigue as assessed by the PROMIS scale

  Baseline, 3 months, 6 months and every 6 months up to 72 months

• Change in anxiety as assessed by the PROMIS scale

  Baseline, 3 months, 6 months and every 6 months up to 72 months

Study Arms (2)

Roflumilast arm

ACTIVE COMPARATOR

Participants will receive prescription for Roflumilast (250 mcg/day x 4 weeks, then 500 mcg/day or alternate regimen) x 6 to 72 months

Drug: Roflumilast

Azithromycin arm

ACTIVE COMPARATOR

Participants will receive prescription for Azithromycin (250 mg/day, or 500 mg three times per week, or alternate regimen) x 6 to 72 months

Drug: Azithromycin

Interventions

Roflumilast DRUG

Prescription for Roflumilast (250 mcg/day x 4 weeks, then 500 mcg/day or alternate regimen) x 6 to 72 months

Also known as: Daliresp

Roflumilast arm

Azithromycin DRUG

Prescription for Azithromycin (250 mg/day, or 500 mg three times per week, or alternate regimen) x 6 to 72 months

Also known as: Zithromax

Azithromycin arm

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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 physician 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(note patients prescribed or using SABA, 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

Sponsors & Collaborators

• Johns Hopkins University: lead
• Patient-Centered Outcomes Research Institute: collaborator
• University of Illinois at Chicago: collaborator

Study Sites (29)

University of Alabama

Birmingham, Alabama, 35233, United States

Location

University of Arizona

Tucson, Arizona, 85734, United States

Location

University of California, Davis Health

Sacramento, California, 95817, United States

Location

Northwestern

Chicago, Illinois, 60611, United States

Location

University of Illinois, Chicago

Chicago, Illinois, 60612, United States

Location

NorthShore Hospital

Glenview, Illinois, 60026, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas

Kansas City, Kansas, 66160, United States

Location

Ochsner Medical Center

New Orleans, Louisiana, 70121, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

Baystate Health

Springfield, Massachusetts, 01199, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

University of Missouri, Kansas City

Kansas City, Missouri, 64108, United States

Location

Northern Westchester Hospital/Northwell Health

Mount Kisco, New York, 10549, United States

Location

Mount Sinai

New York, New York, 10029, United States

Location

Lenox Hill Hospital/Northwell Health

New York, New York, 10075, United States

Location

University of North Carolina, School of Medicine

Chapel Hill, North Carolina, 27599, United States

Location

Duke

Durham, North Carolina, 27705, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Kaiser Permanente

Portland, Oregon, 97227, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

University of Pittsburg Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Baylor Scott & White (BSW) Health-North

Dallas, Texas, 75246, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

University of Vermont

Burlington, Vermont, 05401, United States

Location

Providence Health and Services

Spokane, Washington, 99204, United States

Location

MeSH Terms

Conditions

Bronchitis, Chronic; Pulmonary Disease, Chronic Obstructive

Interventions

Roflumilast; Azithromycin

Condition Hierarchy (Ancestors)

Bronchitis; Respiratory Tract Infections; Infections; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Jerry Krishnan, MD, PhD

  University of Illinois Chicago

  PRINCIPAL INVESTIGATOR

• Robert Wise, MD

  Johns Hopkins School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• 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., they will know the treatment assignment
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The trial is a parallel, pragmatic non-inferiority trial with two treatment groups, roflumilast and azithromycin. Up to 1,250 participants will be randomized (1:1) to receive a prescription for one of the two treatments. Treatment assignments will be stratified by site and smoking status (former versus current) using a permuted block design with multiple block sizes.

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: March 6, 2026

Record last verified: 2026-03

Locations

US (29)