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Completed

NCT Number: NCT04075331

Mepolizumab for COPD Hospital Eosinophilic Admissions Pragmatic Trial

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.

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Key information

Conditions

COPD Chronic Disease Disease Attributes Eosinophilia Hematologic Diseases Hemic and Lymphatic Diseases Leukocyte Disorders Lung Diseases Lung Diseases, Obstructive Pathologic Processes Pathological Conditions, Signs and Symptoms Pulmonary Disease, Chronic Obstructive Respiratory Tract Diseases

Age range

40 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

NIHR Biomedical Research Centre, Respiratory

Leicester, Leicestershire, LE1 9QP, United Kingdom

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

Mepolizumab

Drug

Mepolizumab 100mg subcutaneous injection

Placebo

Drug

Saline solution for subcutaneous injection

Other names: Saline solution

Primary outcomes

  1. Time From Randomisation to Next Hospital Readmission or Death (All Cause)

    Time frame: 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.

Secondary outcomes

  1. Total Number of Hospital Readmissions All Cause Over 48 Weeks

    Time frame: 0-48 weeks

    The number of hospital readmissions (all cause) in total during the 48 (truncated follow-up minimum 24) weeks corresponding to each participant were calculated. Where no hospital admission have occurred a value of zero was derived.

  2. Total Number of Moderate Exacerbations Over 48 Weeks

    Time frame: 48 weeks

    The severity of a COPD exacerbation was deemed as "Moderate" if the participant required treatment with steroids or antibiotics and was not hospitalised .

    The number of moderate exacerbations each participant had over the course of 48 (truncated follow-up minimum 24) weeks were calculated.

  3. Total Number of Severe Exacerbations Over 48 Weeks

    Time frame: 48 weeks

    The severity of a COPD exacerbation was deemed as "Severe" if the participant required hospitalisation.

    The number of severe exacerbations each participant had over the course of 48 (truncated follow-up minimum 24) weeks were calculated.

  4. Total Number of Exacerbations Over 48 Weeks

    Time frame: 48 weeks

    The number of exacerbations each participant had over the course of 48 (truncated follow-up minimum 24) weeks were calculated.

  5. Time From Randomisation to Next Hospital Readmission or Death Due to a Respiratory Cause

    Time frame: 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).

    The time from randomisation to next hospital readmission or death (due to a respiratory cause) is defined as a time to event outcome measured in days. The date of randomisation as well as the date of readmission or death due to respiratory causes (whichever occurs first) were used to calculate time to event. For participants not experiencing an event the time was calculated from randomisation until last known follow-up assessment event-free.

  6. Time From Randomisation to Treatment Failure

    Time frame: 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).

    Treatment failure is defined as the composite of three endpoints: 1. treatment intensification with systemic corticosteroids and/or antibiotics for respiratory reasons; 2. step-up in hospital care for respiratory reasons including transfer to the intensive care unit or readmission; or 3. all-cause mortality)

  7. Hospital Readmission (Respiratory Cause)

    Time frame: Patients were followed up for up to 48 weeks (48 week visit had a window of +/- 1 week).

    Hospital readmission (respiratory cause). Number of individuals that readmitted during follow up is reported. Hospital readmission due to respiratory cause was analysed as a time to event outcome.

  8. Time From Randomisation to Next Hospital Readmission (All Cause)

    Time frame: 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).

    The time from randomisation to next hospital readmission (all cause) is defined as a time to event outcome measured in days. The date of randomisation and the date of next hospital readmission following randomisation was used to calculate time to event. Where hospital readmission doesn't occur during follow-up, time was measured until the participant's last known follow-up assessment.

  9. Death (All Cause)

    Time frame: Patients were followed up for up to 48 weeks (48 week visit had a window of +/- 1 week).

    All cause death. Number of individuals that died during follow up is reported. Death was analysed as a time to event outcome.

  10. Death (Respiratory Cause)

    Time frame: Patients were followed up for up to 48 weeks (48 week visit had a window of +/- 1 week).

    Respiratory cause death. Number of individuals that died during follow up is reported. Death due to respiratory cause was analysed as a time to event outcome.

  11. Extended Medical Research Council Dyspnoea Score (eMRC)

    Time frame: Weeks 0, 4, 8, 12, 24, 36, 48

    This scale measures perceived respiratory disability. Participants rate their grades of breathlessness on a scale of 1 (least) to 5 (worst). The extension divides the grade 5 rating into 'a' (independent) and 'b' (dependent) to establish dependence on others for washing and dressing.

  12. St George's Respiratory Questionnaire (SGRQ)

    Time frame: Weeks 0, 4, 8, 12, 24, 36, 48

    This 50-item questionnaire measures health status (quality of life) in patients with diseases of airway obstruction. Scores are broken down into three components 'symptoms', 'activity', 'impacts', and the total score is calculated by summing the weights to all the positive responses in each component. For each subscale and the total score, values range from 0 (no impairment) to 100 (maximum impairment). Higher values represent a worse outcome.

  13. COPD Assessment Tool (CAT)

    Time frame: Weeks 0, 4, 8, 12, 24, 36, 48

    The COPD Assessment Test (CAT) is a questionnaire for people with Chronic Obstructive Pulmonary Disease (COPD). It is designed to measure the impact of COPD on a person's life, and how this changes over time. Scores range from 0-40, with higher scores indicating greater impact of COPD on a patient's life.

  14. Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS)

    Time frame: Weeks 0, 4, 8, 12, 24, 36, 48

    This scale measures mental wellbeing using a 14-item scale. The scoring range for each item is from 1 - 5 and the total score is from 14-70, with higher scores indicating better mental wellbeing.

  15. London Chest Activities of Daily Living Questionnaire (LCADL)

    Time frame: Weeks 0, 4, 8, 12, 24, 36, 48

    This 15-item questionnaire measures dyspnoea during routine daily activities in patients with COPD. It consists of four components: 'Self-care', 'household activities', 'Physical activity' and 'Leisure activities'. The questions in each of the four domains are scored as follows: 0 ("I wouldn't do it anyway"), 1 ("I do not get breathless"), 2 ("I get moderately breathless"), 3 ("I get very breathless"), 4 ("I have given this up") and 5 ("Someone else does this for me"). The LCADL total score sums all individual questions to give values in the range 0 to 75 (inclusive), with the highest score representing maximal disability.

  16. Short Physical Performance Battery (SPPB)

    Time frame: Weeks 0, 4, 8, 12, 24, 36, 48

    SPPB ranges from 0 (worst performance) to 12 (best performance). This outcome measures lower extremity function using tasks that are similar to daily activities and it examines 3 areas: static balance, gait speed and getting in and out of a chair. The limitations based on the SPPB cut-off scores are defined as follows: "Severe limitations" if score is between 0-3, "Moderate limitations" if score is between 4-6, "Mild limitations" if score is between 7-9 and "Minimal limitations" if score is between 10-12. Lower scores indicate greater impairment.

  17. Handgrip Strength

    Time frame: Weeks 0, 4, 8, 12, 24, 36, 48

    Handgrip strength is defined as a continuous outcome that measures the amount of static force that the hand can squeeze around a dynamometer. This outcome is measured in Kilograms.

  18. Percentage Sputum Eosinophil Count (Inflammatory Markers)

    Time frame: Weeks 0, 4, 8, 12, 24, 36, 48

    The sputum eosinophil count (percentage) is defined as a continuous outcome that is expressed as a percentage.

  19. Total Serum Eosinophil Count (Inflammatory Markers)

    Time frame: Weeks 0, 4, 8, 12, 24, 36, 48

    The serum eosinophil count is defined as a continuous outcome that is measured in cells/mL.

  20. Adverse Events (AEs)

    Time frame: 48 weeks

    Adverse Event Rate in the 48 Weeks of the Trial From First Dose

  21. Serious Adverse Events (SAEs)

    Time frame: 48 weeks

    Serious adverse event rate over 48 week.

  22. Pre Dose Systolic Blood Pressure (mmHg)

    Time frame: Over 48 weeks

    Blood pressure are defined as continuous outcomes that are measured in mmHg and reported as mean over 48 weeks.

  23. Post Dose Systolic Blood Pressure (mmHg)

    Time frame: Over 48 weeks

    Blood pressure are defined as continuous outcomes that are measured in mmHg and reported as mean over 48 weeks.

  24. Pre Dose Diastolic Blood Pressure (mmHg)

    Time frame: Over 48 weeks

    Pre and post dose blood pressure are defined as continuous outcomes that are measured mmHg and reported as mean over 48 weeks.

  25. Post Dose Diastolic Blood Pressure (mmHg)

    Time frame: Over 48 weeks

    Pre and post dose blood pressure are defined as continuous outcomes that are measured mmHg and reported as mean over 48 weeks.

  26. Pre Dose Heart Rate (Beats Per Minute)

    Time frame: Over 48 weeks

    Pre and post dose heart rate are defined as continuous outcomes that are measured beats per minute (bpm) and reported as mean over 48 weeks.

  27. Post Dose Heart Rate (Beats Per Minute)

    Time frame: Over 48 weeks

    Pre and post dose heart rate are defined as continuous outcomes that are measured beats per minute (bpm) and reported as mean over 48 weeks.

  28. Pre Dose Temperature (°C)

    Time frame: Over 48 weeks

    Pre and post dose temperature are defined as continuous outcomes that are measured in °C and reported as mean over 48 weeks.

  29. Post Dose Temperature (°C)

    Time frame: Over 48 weeks

    Pre and post dose temperature are defined as continuous outcomes that are measured in °C and reported as mean over 48 weeks.

Sponsors and collaborators

Lead sponsor

University of Leicester

Other

Collaborators

  • GlaxoSmithKline

Registry information

Official study title

A Randomised Controlled Trial of Mepolizumab Initiated Following Admission to Hospital for a Severe Exacerbation of Eosinophilic COPD

Acronym: COPD-HELP

Important dates

Study start
2020
Primary completion
2024
Study completion
2024
First posted
Aug 30, 2019
Registry last updated
Apr 24, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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