Roflumilast or Azithromycin to Prevent COPD Exacerbations Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,032
- 试验地点
- 48
- 主要终点
- Number of All-cause hospitalizations
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
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., will know the treatment assignment
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 clinician of severe COPD and associated chronic bronchitis
- •Hospitalized with a diagnosis of COPD exacerbation or respiratory complications due to Coronavirus Disease 2019 (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 Short-Acting Beta-Agonist (SABA), Short-Acting Muscarinic Antagonist (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
排除标准
- •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
- •Current treatment with long-term (more than 30 days) roflumilast, azithromycin or ensifentrine (previous treatment with 1 or more doses of azithromycin, roflumilast or ensifentrine 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
- •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.
研究组 & 干预措施
Roflumilast arm
Participants will receive prescription for Roflumilast (250 mcg/day x 4 weeks, then 500 mcg/day or alternate regimen) x 6 to 72 months
干预措施: Roflumilast (Drug)
Azithromycin arm
Participants will receive prescription for Azithromycin (250 mg/day, or 500 mg three times per week, or alternate regimen) x 6 to 72 months
干预措施: Azithromycin (Drug)
结局指标
主要结局
Number of All-cause hospitalizations
时间窗: Up to 72 months
All-cause hospitalizations
Number of All-cause deaths
时间窗: Up to 72 months
All-cause deaths
Time to first all-cause hospitalization or all-cause death
时间窗: Baseline to study exit (up to 72 months)
Composite time-to-event outcome defined as time from randomization to the first occurrence of all-cause hospitalization or all-cause death.
次要结局
- 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 fatigue as assessed by the PROMIS scale(Baseline, 3 months, 6 months and every 6 months up to 72 months)
- Change in depression as assessed by the PROMIS scale(Baseline, 3 months, 6 months and every 6 months up to 72 months)
- Number of Adverse Events(Up to 72 months)
- Time to first all-cause hospitalization(Baseline to study exit (up to 72 months))
- Time to first moderate COPD exacerbation, all-cause hospitalization, or all-cause death(Baseline to study exit (up to 72 months))
- Time to first moderate COPD exacerbation(Baseline to study exit (up to 72 months))
- Time to all-cause death(Baseline to study exit (up to 72 months))
- Change in physical function as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS) scale(Measured at study registration, 3 months, and 6 months)
- Change in sleep disturbance as assessed by the PROMIS scale(Measured at study registration 3 months, and 6 months)
- Change in fatigue as assessed by the PROMIS scale(Measured at study registration 3 months, and 6 months)
- Change in anxiety as assessed by the PROMIS scale(Measured at study registration, 3 months, and 6 months)
- Change in depression as assessed by the PROMIS scale(Measured at study registration, 3 months, and 6 months)
- Rate of Difficulty hearing or ringing in ears(1 week until study exit (up to 72 months)])
- Rate of Diarrhea(1 week until study exit (up to 72 months))
- Rate of Nausea(1 week until study exit (up to 72 months)
- Number of participants reporting thoughts of suicide or self-harm(1 week until study exit (up to 72 months)
- Macrolide-resistant organisms in sputum(Randomization to study exit (up to 72 months))
- Proportion of participants reporting treatment adherence at 1 week(I week)
- Proportion of participants reporting treatment adherence at 3 months(3 months)
- Proportion of Participants reporting Treatment adherence from 6 months to study exit (up to 72 months)(6 months to study exit (up to 72 months))
- Number of participants who switch to alternate study treatment(1 week, 3 months, 6 months and every 6 months up to 72 months)
- Out of pocket cost for study treatment(1 week, 3 months, 6 months and every 6 months up to 72 months)
- Change in weight (pounds)(Measured at baseline, 3 months, and 6 months)
- Number of participants who discontinued assigned study treatment(1 week, 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)
- Change in problems with sleep as assessed by the PROMIS scale(Baseline, 3 months, 6 months and every 6 months up to 72 months)
- 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 depression as assessed by the PROMIS scale(Baseline, 3 months, 6 months and every 6 months up to 72 months)
- Number of Adverse Events(Up to 72 months)
- Medication Adherence as assessed by patient self-report(Up to 72 months)
- Number of participants that switch to alternate study medication(Up to 72 months)
- Out of pocket cost for study medication(Up to 72 months)
- Change in weight(3 and 6 months)
- Number of participants that discontinued medication(Up to 72 months)