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Roflumilast or Azithromycin to Prevent COPD Exacerbations (RELIANCE) (RELIANCE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04069312
Recruitment Status : Recruiting
First Posted : August 28, 2019
Last Update Posted : March 3, 2020
Sponsor:
Collaborator:
Patient-Centered Outcomes Research Institute
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:
A multi-center, randomized, 36-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.

Condition or disease Intervention/treatment Phase
Chronic Obstructive Pulmonary Disease Severe Chronic Bronchitis Drug: Roflumilast Drug: Azithromycin Phase 3

Detailed Description:

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 3,200 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 36 months. The primary endpoint is the combined outcome of all-cause hospitalization or death; the secondary endpoints include premature treatment discontinuation, patient-reported adverse effects, and physical, social, and emotional health. 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 and administrative/claims databases.

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The trial is a parallel, pragmatic non-inferiority trial with two treatment groups, roflumilast and azithromycin. Up to 3,200 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.
Masking: None (Open Label)
Masking Description: 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
Primary Purpose: Other
Official Title: Roflumilast or Azithromycin to Prevent COPD Exacerbations (RELIANCE)
Actual Study Start Date : February 11, 2020
Estimated Primary Completion Date : February 2023
Estimated Study Completion Date : February 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Roflumilast arm
Participants will receive prescription for Roflumilast (250 mcg/day x 4 weeks, then 500 mcg/day or alternate regimen) x 6 to 36 months
Drug: Roflumilast
Prescription for Roflumilast (250 mcg/day x 4 weeks, then 500 mcg/day or alternate regimen) x 6 to 36 months
Other Name: Daliresp

Active Comparator: Azithromycin arm
Participants will receive prescription for Azithromycin (250 mg/day, or 500 mg three times per week, or alternate regimen) x 6 to 36 months
Drug: Azithromycin
Prescription for Azithromycin (250 mg/day, or 500 mg three times per week, or alternate regimen) x 6 to 36 months
Other Name: Zithromax




Primary Outcome Measures :
  1. Number of All-cause hospitalizations [ Time Frame: Up to 36 months ]
    All-cause hospitalizations

  2. Number of All-cause deaths [ Time Frame: Up to 36 months ]
    All-cause deaths


Secondary Outcome Measures :
  1. Number of All-cause individual events [ Time Frame: Up to 36 months ]
    All-cause individual events

  2. Change in physical function as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS) scale [ Time Frame: Baseline, 3 months, 6 months and every 6 months up to 36 months ]
    Based on the scoring scale; a score of 5 is the most favorable and a score of 1 is least favorable.

  3. Change in problems with sleep as assessed by the PROMIS scale [ Time Frame: Baseline, 3 months, 6 months and every 6 months up to 36 months ]
    1 is least favorable and 5 is most favorable

  4. Change in fatigue as assessed by the PROMIS scale [ Time Frame: Baseline, 3 months, 6 months and every 6 months up to 36 months ]
    0 is most favorable and 4 and least favorable

  5. Change in anxiety as assessed by the PROMIS scale [ Time Frame: Baseline, 3 months, 6 months and every 6 months up to 36 months ]
    Score of 1 is most favorable and 5 is least favorable

  6. Change in depression as assessed by the PROMIS scale [ Time Frame: Baseline, 3 months, 6 months and every 6 months up to 36 months ]
    1 is most favorable and 5 is least favorable

  7. Number of Adverse Events [ Time Frame: Up to 36 months ]
    Adverse events

  8. Medication Adherence as assessed by patient self-report [ Time Frame: Up to 36 months ]
    Medication Adherence will be assessed by self-report via Call Center or Patient Portal; Medicare claims data in a subset.

  9. Number of participants that switch to alternate study medication [ Time Frame: Up to 36 months ]
    Patient will be assigned either azithromycin or roflumilast at randomization. We will assess any switch to either roflumilast from azithromycin or azithromycin from roflumilast by self-report via Call Center or Patient Portal, query of clinic staff; Medicare claims data in a subset

  10. Out of pocket cost for study medication [ Time Frame: Up to 36 months ]
    Out of pocket costs for roflumilast of azithromycin by self-report via Call Center or Patient Portal

  11. Change in weight [ Time Frame: 3 and 6 months ]
    Weight in lbs

  12. Number of participants that discontinued medication [ Time Frame: Up to 36 months ]
    This will be collected by self-report via Call Center or Patient Portal; query of clinic staff; Medicare claims data in a subset



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04069312


Contacts
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Contact: Gem Roy, MD 4432875796 groy2@jhu.edu

Locations
Show Show 32 study locations
Sponsors and Collaborators
Johns Hopkins University
Patient-Centered Outcomes Research Institute
Investigators
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Principal Investigator: Jerry Krishnan, MD, PhD University of Illinois, Chicago
Principal Investigator: Robert Wise, MD Johns Hopkins School of Medicine
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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT04069312    
Other Study ID Numbers: IRB00179281
First Posted: August 28, 2019    Key Record Dates
Last Update Posted: March 3, 2020
Last Verified: March 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Johns Hopkins University:
Chronic Obstructive Pulmonary Disease
Chronic Bronchitis
COPD
Roflumilast
Daliresp
Azithromycin
Additional relevant MeSH terms:
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Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Bronchitis
Bronchitis, Chronic
Respiratory Tract Diseases
Bronchial Diseases
Respiratory Tract Infections
Azithromycin
Anti-Bacterial Agents
Anti-Infective Agents