A Phase 3 interventional study of Roflumilast and Azithromycin in Chronic Obstructive Pulmonary Disease Severe and Chronic Bronchitis, sponsored by Johns Hopkins University. Completed at 28 sites in United States. Open to participants aged 40 Years and older. Per ClinicalTrials.gov, last updated 2026-08-21.
Sponsored by Johns Hopkins University · Phase 3, Interventional, and Treatment
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.
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. 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.
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).
209 studies on the registry are indexed under Bronchitis, Chronic; 14 are open to participants now.
This study's enrollment of 1,032 is above the median of 101 across 154 interventional studies indexed under Bronchitis, Chronic.
Browse Bronchitis, Chronic studies →Johns Hopkins University is the lead sponsor of 1,815 studies on the registry; 315 are open to participants now.
Of its 208 completed or terminated interventional studies of FDA-regulated products, 144 (69%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
COPD
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
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
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
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.
Time frame: Baseline to study exit (up to 72 months)
Time to first moderate COPD exacerbation, all-cause hospitalization, or all-cause death
Composite time-to-event outcome defined as time from randomization to the first occurrence of moderate COPD exacerbation, all-cause hospitalization, or all-cause death. Moderate COPD exacerbation is defined as treatment with antibiotics or systemic corticosteroids for a respiratory exacerbation not associated with hospitalization.
Time frame: Baseline to study exit (up to 72 months)
Time to first moderate COPD exacerbation
Time from randomization to the first moderate COPD exacerbation.
Time frame: Baseline to study exit (up to 72 months)
Time to first all-cause hospitalization
Time from randomization to the first all-cause hospitalization.
Time frame: Baseline to study exit (up to 72 months)
Time to all-cause death
Time from randomization to all-cause death.
Time frame: Baseline to study exit (up to 72 months)
Change in physical function as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS) scale
Change in physical function from study registration to 6 months using the PROMIS physical function measure. Higher scores indicate better physical function. Score range 1-5 (i.e., a score of 5 is the most favorable and a score of 1 is least favorable).
Time frame: Measured at study registration, 3 months, and 6 months
Change in sleep disturbance as assessed by the PROMIS scale
Change in sleep disturbance from study registration to 6 months using the PROMIS sleep disturbance measure. Lower scores indicate more sleep disturbance. Score range 1-5 (i.e., a score of 1 is most favorable and 5 is least favorable).
Time frame: Measured at study registration 3 months, and 6 months
Change in fatigue as assessed by the PROMIS scale
Change in fatigue from study registration to 6 months using the PROMIS fatigue measure. Higher scores indicate greater fatigue. Score range 0-4 (i.e., a score of 0 is most favorable and 4 is least favorable).
Time frame: Measured at study registration 3 months, and 6 months
Change in anxiety as assessed by the PROMIS scale
Change in anxiety from study registration to 6 months using the PROMIS anxiety measure. Higher scores indicate greater anxiety. Score range 1-5 (i.e., a score of 1 is most favorable and 5 is least favorable).
Time frame: Measured at study registration, 3 months, and 6 months
Change in depression as assessed by the PROMIS scale
Change in depression from study registration to 6 months using the PROMIS depression measure. Higher scores indicate greater depression. Score range 1-5 (i.e., a score of 1 is most favorable and 5 is least favorable).
Time frame: Measured at study registration, 3 months, and 6 months
Rate of Difficulty hearing or ringing in ears
Event rate (per person-year) reporting difficulty hearing or ringing in ears during follow-up
Time frame: 1 week until study exit (up to 72 months)]
Rate of Diarrhea
Event rate (per person-year) reporting diarrhea during follow-up
Time frame: 1 week until study exit (up to 72 months)
Rate of Nausea
Event rate (per person-year) reporting nausea during follow-up
Time frame: 1 week until study exit (up to 72 months
Number of participants reporting thoughts of suicide or self-harm
Number of participants reporting suicidal ideation during follow-up
Time frame: 1 week until study exit (up to 72 months
Macrolide-resistant organisms in sputum
The number of participants with a positive sputum test for macrolide resistant organisms in the subset of participants whose electronic health record included testing while in the study
Time frame: Randomization to study exit (up to 72 months)
Proportion of participants reporting treatment adherence at 1 week
Proportion of participants reporting use of assigned treatment at 1 week
Time frame: I week
Proportion of participants reporting treatment adherence at 3 months
Proportion of participants reporting use of assigned study treatment at 3 months.
Time frame: 3 months
Proportion of Participants reporting Treatment adherence from 6 months to study exit (up to 72 months)
For each participant, adherence is defined as the proportion of evaluable follow-up assessments at which the participant reports use of assigned study treatment. The outcome summarizes participant-reported adherence across follow-up from 6 months to study exit (up to 72 months) among participants with at least one evaluable medication use assessment as an event rate (per person year).
Time frame: 6 months to study exit (up to 72 months)
Number of participants who switch to alternate study treatment
Number of participants with any follow-up report of prescription for the alternative study treatment after randomization.
Time frame: 1 week, 3 months, 6 months and every 6 months up to 72 months
Out of pocket cost for study treatment
Participant-reported out-of-pocket cost (measured in U.S. dollars) for assigned study treatment.
Time frame: 1 week, 3 months, 6 months and every 6 months up to 72 months
Change in weight (pounds)
Change from baseline in participant-reported weight (measured in pounds)
Time frame: Measured at baseline, 3 months, and 6 months
Number of participants who discontinued assigned study treatment
Number of participants meeting protocol-defined treatment discontinuation, defined as the earliest follow-up assessment at which the participant reports not taking assigned study treatment during the interval since the prior assessment, with no subsequent report of treatment use. Because medication use is collected over recall intervals rather than exact stop dates, discontinuation reflects the earliest follow-up time point consistent with persistent non-use of assigned study treatment.
Time frame: 1 week, 3 months, 6 months and every 6 months up to 72 months
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — 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.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, 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.
Data sharing details ↗ · www.icpsr.umich.edu
This study is completed, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Roflumilast · Azithromycin