Mepolizumab and exacerbation frequency in refractory eosinophilic asthma: a randomised, double blind, placebo controlled trial
| ISRCTN | ISRCTN75169762 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN75169762 |
| Secondary identifying numbers | 125770 |
- Submission date
- 04/05/2005
- Registration date
- 10/08/2005
- Last edited
- 10/03/2009
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Prof Ian Pavord
Scientific
Scientific
Glenfield Hospital
Groby Road
Leicester
LE3 9QP
United Kingdom
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Scientific title | |
| Study objectives | Mepolizumab which is a monoclonal antibody against interleukin 5, will effectively suppress eosinophilic airway inflammation and lower exacerbation frequency in severe asthmatics with evidence of persistent eosinophilic airway inflammation and a history of recurrent asthma exacerbations (greater than or equal to 2/year). The hypothesis is based upon previous studies that have demonstrated a temporal relationship between a rise in sputum eosinophilia predicting onset of exacerbations. Steroid therapy targeted at lowering sputum eosinophil counts have been effective in lowering exacerbation frequency. Following on from this, mepolizumab has been shown in pilot studies to be effective in lowering both blood and sputum eosinophil counts and if the previous observations are robust in their hypothesis that sputum eosinophilia is causally related to asthma exacerbations, then we would expect mepoloizumab to achieve control of exacerbations through its mechanism of action. The present study has been designed to test this hypothesis. |
| Ethics approval(s) | Obtained before recruitment of the first participant. |
| Health condition(s) or problem(s) studied | Asthma |
| Intervention | 12 month randomised double blind placebo contolled parallel group trial to receive either placebo or monoclonal antibody therapy to interleukin 5 (mepolizumab) - 750 mg intravenously over 30 minutes, monthly. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Mepolizumab |
| Primary outcome measure | Sputum eosinophil counts measured every 3 months and exacerbation frequency over the 12 month treatment period. We have 80% power to detect a 50% change in exacerbation frequency over 1 year for a total of 60 trial participants. |
| Secondary outcome measures | 1. Asthma symptoms and quality of life 2. Computed tomography (CT) and bronchial biopsy evidence of airway remodelling (i.e. structural changes to the airway wall from long standing chronic airway inflammation) |
| Overall study start date | 01/08/2005 |
| Completion date | 31/07/2007 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 60 |
| Key inclusion criteria | 1. 60 participants meeting American thoracic criteria for refractory asthma 2. On intensive corticosteroid therapy - either oral and/or inhaled 3. A history of two or more exacerbations of asthma requiring oral corticosteroid rescue therapy in one year 4. Evidence of persistent eosinophilic inflammation in sputum - sputum eosinophils greater than 3% of total cell count |
| Key exclusion criteria | 1. Participants who do not meet American Thoracic Society criteria for severe asthma 2. Participants who have not demonstrated evidence of persistent eosinophilic airway inflammation (sputum eosinophil counts of greater than or equal to 3% of total cell count 3. Partcipants who are current smokers or who have a cumulative smoking history of greater than 15 pack years 4. Participants with significant co morbidity - including other symptomatic respiratory diagnoses, evidence of recurrent bacterial respiratory tract infections (greater than or equal to 2 per year), symptomatic ischaemic heart disease and mental health or other conditions that interfere with participant compliance with the study 5. Pregnant females or women of child bearing age not practising effective contraception during the study |
| Date of first enrolment | 01/08/2005 |
| Date of final enrolment | 31/07/2007 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Glenfield Hospital
Leicester
LE3 9QP
United Kingdom
LE3 9QP
United Kingdom
Sponsor information
University Hospitals of Leicester NHS Trust (UK)
University/education
University/education
Glenfield Hospital
Groby Road
Leicester
LE3 9QP
England
United Kingdom
| Website | http://www.uhl-tr.nhs.uk/ |
|---|---|
"ROR" |
https://ror.org/02fha3693 |
Funders
Funder type
Government
University Hospitals of Leicester NHS Trust (UK)
No information available
Added as of 02/01/2008:
No information available
GlaxoSmithKline (UK)
Government organisation / For-profit companies (industry)
Government organisation / For-profit companies (industry)
- Alternative name(s)
- GlaxoSmithKline plc., GSK plc., GSK
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 05/03/2009 | Yes | No |
