This study is designed to look why patients with severe asthma fail to respond to oral corticosteroids in the same way as patients with non-severe disease. MedDRA version: 14.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Trade Name: Prednisolone
Product Name: Prednisolone
Pharmaceutical Form: Tablet
INN or Proposed INN: PREDNISOLONE
CAS Number: 50248
Sponsors
Imperial College
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Severe asthma subjects: Physician diagnosis of asthma Aged 18 – 70 Non-smokers or ex-smokers with less than 5 pack/year history Major characteristics (at least one of the following criteria) • Treatment with continuous or near continuous (>50% of year) oral corticosteroids • Requirement for treatment with high dose inhaled corticosteroids (ICS) Minor characteristics (at least 2 out of the following) 1. Requirement for daily treatment with a controller medication in addition to ICS e.g. LABA, theophylline, leukotriene antagonist 2. Asthma symptoms requiring SABA on a daily or near daily basis 3. Persistent airways obstruction (FEV1 20%) 4. One or more emergency care visits for asthma per year 5. 3 or more steroid “bursts” per year 6. Prompt deterioration with = 25% reduction in oral or ICS 7. Near fatal asthma event in the past Moderately-severe asthma: Physician diagnosis of asthma Aged 18 – 70 Non-smokers or ex-smokers with less than 5 pack/year history Less than 2 courses of prednisolone per year Taking up to 2000 mcg of inhaled corticosteroid (BDP equivalent) per day Stable asthma for at least 6 months prior to enrolment Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Current smokers, or less than 3 years since quitting smoking Less than 4 weeks from an exacerbation Diabetes Active peptic ulceration Previous history of psychiatric disturbances on high dose prednisolone On steroid-sparing agent or immunosuppressant such as azathioprine, methotrexate and ciclosporin Concomitant anti-IgE therapy Pregnancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This study is to establish why severe asthmatic patients do not respond to oral corticosteroids as do non-severe asthmatics - is it due to abnormal/subtherapeutic levels or inability to exert its anti-inflammatory effects? Aims and objectives 1. To evaluate blood prednisolone levels and their anti-inflammatory effects in two severe asthma groups, comparing patients on inhaled corticosteroids (ICS) alone to those on ICS plus oral prednisolone, and a group of well-controlled moderately severe asthmatics. 2. To evaluate if a 14-day course of prednisolone affects ‘spot’(one-off) measurements of prednisolone levels, and if these are influenced by taking regular prednisolone 3. To determine the relationship between blood levels of prednisolone and its anti-inflammatory effects Primary endpoints: 1. serum prednisolone levels over 24 hours 2. change in FEV1 24 hours post prednisolone 3. changes in eNO, sputum eosinophils and inflammatory mediators over 24 hours ; Secondary Objective: Secondary endpoints: 1. difference between day 1 and day 14 in serum prednisolone levels 2. difference in FEV1 between day 1 and day 14 3. difference in eNO, sputum eosinophils and inflammatory mediators between day 1 and day 14 4. changes in asthma control symptoms before and after treatment ; Primary end point(s): Primary endpoints: 1. serum prednisolone levels over 24 hours 2. change in FEV1 24 hours post prednisolone 3. changes in eNO, sputum eosinophils and inflammatory mediators over 24 hours 4. levels of activated GR (glucocorticoid receptor) | — |
Countries
United Kingdom
Outcome results
None listed