Roflumilast vs Azithromycin for COPD Exacerbations

(RELIANCE Trial)

Recruiting in Palo Alto (17 mi)

+32 other locations

Overseen by Robert Wise, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Johns Hopkins University

Must be taking: LAMA, LABA, ICS

Must not be taking: Macrolides, Ketolides

Disqualifiers: Liver impairment, Pregnancy, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications. However, it mentions that participants can continue using inhaled medications like LAMA, LABA, or ICS/LABA.

What data supports the effectiveness of the drug Roflumilast for COPD exacerbations?

Roflumilast has been shown to improve lung function and reduce the rate of COPD exacerbations in patients with moderate to severe COPD, especially those with chronic bronchitis. In several studies, it was associated with a 17% reduction in exacerbation rates compared to placebo. ^{1 2 3 4 5}

Is Roflumilast safe for humans?

Roflumilast is generally well tolerated in humans, with common side effects including diarrhea, nausea, and weight loss. It may increase the risk of psychiatric issues but does not increase the risk of respiratory infections and may reduce cardiovascular risks. ^{2 3 4 5 6}

How does the drug Roflumilast differ from Azithromycin in treating COPD exacerbations?

Roflumilast is a unique drug for COPD exacerbations because it works by reducing inflammation in the lungs through a different mechanism than Azithromycin, which is an antibiotic that also has anti-inflammatory effects. Roflumilast is specifically designed to target and inhibit an enzyme called phosphodiesterase-4 (PDE4), which helps decrease inflammation, while Azithromycin is primarily used to treat bacterial infections and has additional benefits in reducing COPD exacerbations. ^{7 8 9 10 11}

Research Team

Jerry Krishnan, MD

Principal Investigator

University of Illinois Chicago

Robert Wise, MD

Principal Investigator

Johns Hopkins School of Medicine

Eligibility Criteria

This trial is for adults over 40 who have severe COPD with chronic bronchitis, are current or past smokers with a history of at least 10 pack-years, and were hospitalized for COPD exacerbations or respiratory issues from Covid-19 in the last year. They must be on certain inhaled medications and considering additional treatments to prevent further COPD flare-ups.

Inclusion Criteria

I speak English or Spanish.

I was hospitalized for COPD flare-up or COVID-19 breathing issues in the last year.

My doctor and I are considering adding roflumilast or azithromycin to my treatment to prevent worsening of my COPD.

Exclusion Criteria

I've had liver problems after taking azithromycin.

I am currently on a long-term treatment with roflumilast or azithromycin.

I have had a serious reaction to azithromycin or roflumilast.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either roflumilast or azithromycin for 6 to 72 months to prevent COPD exacerbations

6 to 72 months

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

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Azithromycin (Macrolide Antibiotic)
• Roflumilast (Phosphodiesterase-4 (PDE-4) Inhibitor)

Trial Overview The RELIANCE study is testing whether roflumilast (Daliresp) can be as effective as azithromycin in preventing hospitalizations or death among high-risk COPD patients. Participants will randomly receive one of these drugs over a period of six years to compare their effectiveness.

Participant Groups

Group I: Roflumilast arm Active Control 1 Intervention

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

Group II: Azithromycin arm Active Control 1 Intervention

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

Azithromycin is already approved in Canada for the following indications:

Approved in Canada as Azithromycin for:

• Respiratory tract infections
• Skin and soft tissue infections
• Sexually transmitted diseases
• Toxoplasmosis
• Malaria
• Preterm prelabor rupture of membranes

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University Hospitals Cleveland Medical Center Cleveland, OH

University of Kansas Kansas City, KS

Houston Methodist Hospital Houston, TX

Medical University of South Carolina Charleston, SC

More Trial Locations

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2366

Patients Recruited

15,160,000+

University of Illinois at Chicago

Collaborator

Trials

653

Patients Recruited

1,574,000+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Patients Recruited

27,110,000+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Roflumilast added to triple therapy in patients with severe COPD: a real life study. Muñoz-Esquerre, M., Diez-Ferrer, M., Montón, C., et al.[2022]

In a study of 3,875 COPD patients, roflumilast was associated with higher mortality rates (19%) compared to azithromycin (15%), indicating a potential safety concern for roflumilast.

Roflumilast also showed higher rates of COPD-related and all-cause hospitalizations compared to azithromycin, suggesting it may be less effective in preventing exacerbations in COPD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Roflumilast and Azithromycin for the Treatment of Chronic Obstructive Pulmonary Disease. Lam, J., Tonnu-Mihara, I., Kenyon, NJ., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Roflumilast: A Review in COPD. Garnock-Jones, KP.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PDE4-inhibitors: a novel, targeted therapy for obstructive airways disease. Diamant, Z., Spina, D.[2014]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Roflumilast: in chronic obstructive pulmonary disease. Sanford, M.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential role of roflumilast: the new phosphodiesterase-4 inhibitor. Karish, SB., Gagnon, JM.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azithromycin in the treatment of patients with exacerbation of chronic obstructive pulmonary disease. Płusa, T.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Onset of symptom resolution in adults with acute bacterial rhinosinusitis treated with a single dose of azithromycin extended release compared with 10 days of levofloxacin: a retrospective analysis of a randomized, double-blind, double-dummy trial. Marple, BF., Roberts, CS., de Caprariis, PJ., et al.[2013]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of single-dose 2.0 g azithromycin in the treatment of acute exacerbation of chronic obstructive pulmonary disease. Asai, N., Ohkuni, Y., Iwasaki, T., et al.[2018]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A randomized comparative study of 3 days of azithromycin treatment and 10 days of cefuroxime treatment in exacerbations in patients with chronic obstructive pulmonary disease]. Alvarez Gutiérrez, FJ., Soto Campos, G., del Castillo Otero, D., et al.[2015]

Macrolides, like azithromycin, can help reduce the number of exacerbations in patients with chronic obstructive pulmonary disease (COPD) who frequently experience these episodes.

However, after more than one year of treatment, azithromycin does not maintain its effectiveness in reducing exacerbation frequencies, suggesting that its benefits may diminish over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Azithromycin Maintenance Treatment in Patients with Frequent Exacerbations of Chronic Obstructive Pulmonary Disease. Talman, S., Uzun, S., Djamin, RS., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Roflumilast added to triple therapy in patients with severe COPD: a real life study. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Roflumilast and Azithromycin for the Treatment of Chronic Obstructive Pulmonary Disease. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Roflumilast: A Review in COPD. [2022]

4. England pubmed.ncbi.nlm.nih.gov

PDE4-inhibitors: a novel, targeted therapy for obstructive airways disease. [2014]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Roflumilast: in chronic obstructive pulmonary disease. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

The potential role of roflumilast: the new phosphodiesterase-4 inhibitor. [2022]

7. Poland pubmed.ncbi.nlm.nih.gov

Azithromycin in the treatment of patients with exacerbation of chronic obstructive pulmonary disease. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Onset of symptom resolution in adults with acute bacterial rhinosinusitis treated with a single dose of azithromycin extended release compared with 10 days of levofloxacin: a retrospective analysis of a randomized, double-blind, double-dummy trial. [2013]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of single-dose 2.0 g azithromycin in the treatment of acute exacerbation of chronic obstructive pulmonary disease. [2018]

10. Spain pubmed.ncbi.nlm.nih.gov

[A randomized comparative study of 3 days of azithromycin treatment and 10 days of cefuroxime treatment in exacerbations in patients with chronic obstructive pulmonary disease]. [2015]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Long-Term Azithromycin Maintenance Treatment in Patients with Frequent Exacerbations of Chronic Obstructive Pulmonary Disease. [2021]