A Randomised Controlled Trial of Mepolizumab Initiated Following Admission to Hospital for a Severe Exacerbation of Eosinophilic COPD
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 238
- 试验地点
- 2
- 主要终点
- Time from randomisation to next hospital readmission or death (all cause)
研究概览
简要总结
This is a single-centre, double-blinded, randomised, placebo controlled trial comparing mepolizumab 100mg versus placebo in patients with eosinophilic COPD, started following their index admission to hospital.
详细描述
Patients admitted to hospital with an exacerbation of COPD are at high risk of readmission, of which a proportion are driven by eosinophilic inflammation. Whilst oral corticosteroids are beneficial in exacerbations, a considerable proportion of patients experience treatment failure, with 50% of patients readmitted within 3 months (www.RCPLondon.ac.uk).
Therapy, such as mepolizumab, reduces eosinophil count and has been shown to reduce exacerbation frequency when given in the stable state in both eosinophilic asthma (Papi et al. 2018) and COPD (Yousef, in press).
The investigators hypothesise that starting mepolizumab at the time of a hospitalisation for an exacerbation of COPD in patients with significant eosinophilia will result in a reduction in readmission to hospital in a high risk population.
Therefore, 238 participants will be recruited over an 18-month period and will be randomised into a 48-week treatment period in which they will receive monthly subcutaneous injections of either 100 mg mepolizumab or placebo. Secondary outcomes will be measured at baseline (week 0), 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks and 48 weeks.
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
- Double (Participant, Investigator)
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
- •Symptoms typical of COPD when stable (baseline eMRC dyspnoea grade 2 or more).
- •A clinician defined exacerbation of COPD requiring admission to hospital.
- •Serum eosinophil count of ≥ 300 cells/μL either at time of admission or at any one time in the preceding 12 months.
- •Smoking pack years ≥10 years.
- •Age ≥ 40 years.
- •Established on inhaled corticosteroids (ICS) prior to this admission.
- •Willing and able to consent to participate in trial.
- •Able to understand written and spoken English.
排除标准
- •COPD patients without eosinophilia (defined as persistently < 300 cells/μL within the last 12 months).
- •Other conditions that may be the cause of eosinophilia (such as hypereosinophilic syndrome, eosinophilic granulomatosis, eosinophilic oesophagitis or parasitic infection).
- •Patients whose treatment is considered palliative (life expectancy < 6 months).
- •Other respiratory conditions including active lung cancer, interstitial lung disease, primary pulmonary hypertension or any other conditions that in the view of the investigator will affect the trial.
- •Known history of anaphylaxis or hypersensitivity to mepolizumab or any of the excipients (sucrose, sodium phosphate dibasic heptahydrate, polysorbate 80).
- •Unstable or life-threatening cardiac disease including myocardial infarction or unstable angina in the last 6 months, unstable or life-threatening cardiac arrhythmia requiring intervention in the last 3 months and New York Heart Association (NYHA) Class IV heart failure.
- •Decompensated liver disease or cirrhosis.
- •Pregnant, breastfeeding, or lactating women. Women of child-bearing potential must agree to use appropriate methods of birth control and have a negative blood serum pregnancy test performed after randomisation but prior to first dosing with randomised treatment.*
- •Participation in an interventional clinical trial within 3 months of visit 1 or receipt of any investigational medicinal product within 3 months or 5 half-lives.
- •Known blood born infection (e.g. HIV, hepatitis B or C).
- •Women of child bearing potential (WOCBP) - A woman is defined as being of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal, unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
研究组 & 干预措施
Mepolizumab
Mepolizumab
干预措施: Mepolizumab (Drug)
Placebo
Saline solution
干预措施: Placebo (Drug)
结局指标
主要结局
Time from randomisation to next hospital readmission or death (all cause)
时间窗: 48 weeks
To evaluate the efficacy of mepolizumab initiated following hospitalisation on future hospital readmission or death (all cause) compared with placebo and standard medical therapy in severe exacerbations of eosinophilic COPD.
Time From Randomisation to Next Hospital Readmission or Death (All Cause)
时间窗: Patients were followed up for up to 48 weeks (an absolute maximum of 49 weeks as the 48 week visit had a visit window of +- 1 week).
To evaluate the efficacy of mepolizumab initiated following hospitalisation on future hospital readmission or death (all cause) compared with placebo and standard medical therapy in severe exacerbations of eosinophilic COPD.
次要结局
- Total number of moderate exacerbations over 48 weeks(48 weeks)
- Time from randomisation to death (all cause)(48 weeks)
- Length of index hospital admission(48 weeks)
- Time from randomisation to first hospital readmission or death due to a respiratory cause(48 weeks)
- Total number of hospital readmissions all cause over 48 weeks(48 weeks)
- Time from randomisation to treatment failure(48 weeks)
- Time from randomisation to death (respiratory cause)(48 weeks)
- Time from randomisation to first hospital readmission (all cause)(48 weeks)
- Extended Medical Research Council dyspnoea score (eMRC)(Weeks 0, 4, 8, 12, 24, 36, 48)
- Physical activity using accelerometry(Weeks 0, 4, 8, 12, 24, 36, 48)
- Total Serum eosinophil count (inflammatory markers)(Weeks 0, 4, 8, 12, 24, 36, 48)
- Percentage sputum eosinophil count (inflammatory markers)(Weeks 0, 4, 8, 12, 24, 36, 48)
- Heart Rate (beats per minute)(Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48)
- Blood pressure (systolic/diastolic mmHg)(Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48)
- COPD Assessment Tool (CAT)(Weeks 0, 4, 8, 12, 24, 36, 48)
- Time from randomisation to first hospital readmission (respiratory cause)(48 weeks)
- Warwick-Edinburgh Mental wellbeing scale (WEMWBS)(Weeks 0, 4, 8, 12, 24, 36, 48)
- Short physical performance battery (SPPB)(Weeks 0, 4, 8, 12, 24, 36, 48)
- Temperature (degrees)(Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48)
- St George's Respiratory Questionnaire (SGRQ)(Weeks 0, 4, 8, 12, 24, 36, 48)
- London Chest Activities of Daily Living Questionnaire (LCADL)(Weeks 0, 4, 8, 12, 24, 36, 48)
- Handgrip Strength(Weeks 0, 4, 8, 12, 24, 36, 48)
- Adverse Events (AEs)(48 weeks)
- Serious Adverse Events (SAEs)(48 weeks)
- Total Number of Hospital Readmissions All Cause Over 48 Weeks(0-48 weeks)
- Total Number of Moderate Exacerbations Over 48 Weeks(48 weeks)
- Total Number of Severe Exacerbations Over 48 Weeks(48 weeks)
- Total Number of Exacerbations Over 48 Weeks(48 weeks)
- Time From Randomisation to Next Hospital Readmission or Death Due to a Respiratory Cause(Patients were followed up for up to 48 weeks (an absolute maximum of 49 weeks as the 48 week visit had a visit window of +- 1 week).)
- Time From Randomisation to Treatment Failure(Patients were followed up for up to 48 weeks (an absolute maximum of 49 weeks as the 48 week visit had a visit window of +- 1 week).)
- Hospital Readmission (Respiratory Cause)(Patients were followed up for up to 48 weeks (48 week visit had a window of +/- 1 week).)
- Time From Randomisation to Next Hospital Readmission (All Cause)(Patients were followed up for up to 48 weeks (an absolute maximum of 49 weeks as the 48 week visit had a visit window of +/- 1 week).)
- Death (All Cause)(Patients were followed up for up to 48 weeks (48 week visit had a window of +/- 1 week).)
- Death (Respiratory Cause)(Patients were followed up for up to 48 weeks (48 week visit had a window of +/- 1 week).)
- Extended Medical Research Council Dyspnoea Score (eMRC)(Weeks 0, 4, 8, 12, 24, 36, 48)
- Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS)(Weeks 0, 4, 8, 12, 24, 36, 48)
- Short Physical Performance Battery (SPPB)(Weeks 0, 4, 8, 12, 24, 36, 48)
- Percentage Sputum Eosinophil Count (Inflammatory Markers)(Weeks 0, 4, 8, 12, 24, 36, 48)
- Total Serum Eosinophil Count (Inflammatory Markers)(Weeks 0, 4, 8, 12, 24, 36, 48)
- Pre Dose Systolic Blood Pressure (mmHg)(Over 48 weeks)
- Post Dose Systolic Blood Pressure (mmHg)(Over 48 weeks)
- Pre Dose Diastolic Blood Pressure (mmHg)(Over 48 weeks)
- Post Dose Diastolic Blood Pressure (mmHg)(Over 48 weeks)
- Pre Dose Heart Rate (Beats Per Minute)(Over 48 weeks)
- Post Dose Heart Rate (Beats Per Minute)(Over 48 weeks)
- Pre Dose Temperature (°C)(Over 48 weeks)
- Post Dose Temperature (°C)(Over 48 weeks)