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Comparing Roflumilast and Azithromycin to Prevent COPD Exacerbations

Roflumilast or Azithromycin to Prevent COPD Exacerbations (RELIANCE)

Phase 4 Interventional Johns Hopkins University · NCT04069312

This study is testing whether roflumilast or azithromycin can help prevent hospital visits and deaths in people with severe COPD who are at high risk for flare-ups.

Quick facts

PhasePhase 4
Study typeInterventional
Enrollment1250 (estimated)
Ages40 Years and up
SexAll
SponsorJohns Hopkins University Academic / other
Locations27 sites (Birmingham, Alabama and 26 other locations)
Trial IDNCT04069312 on ClinicalTrials.gov

What this trial studies

This clinical trial compares the effectiveness of roflumilast and azithromycin in preventing hospitalizations or deaths in patients with severe chronic obstructive pulmonary disease (COPD) who are at high risk for exacerbations. Conducted over 72 months, the study will enroll up to 1,250 patients who have been hospitalized for COPD exacerbations in the past year. Participants will be randomized to receive either medication and will be monitored for various health outcomes, including hospitalization rates and adverse effects. The trial aims to provide insights into the relative benefits and harms of these two treatments.

Who should consider this trial

Good fit: Ideal candidates are adults aged 40 and older with severe COPD and a history of recent hospitalization for exacerbations.

Not a fit: Patients who have a history of serious intolerance to either roflumilast or azithromycin may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide clearer guidance on the most effective medication for preventing COPD exacerbations, potentially improving patient outcomes.

How similar studies have performed: While both medications have shown effectiveness in reducing COPD exacerbations, this is the first head-to-head comparison of roflumilast and azithromycin.

Eligibility criteria

Show full inclusion / exclusion criteria 
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

Where this trial is running

Birmingham, Alabama and 26 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Chronic Obstructive Pulmonary Disease SevereChronic BronchitisChronic Obstructive Pulmonary DiseaseCOPDRoflumilastDalirespAzithromycin
Last reviewed 2026-06-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.