None listed
Conditions
Brief summary
Treatment options for severe asthma remain limited and oral corticosteroids (OCS e.g. prednisone) are often needed to control severe asthma when it worsens or flares up. One disadvantage of OCS is their side-effects and therefore any measure that would reduce or eliminate the dose of OCS required would be advantageous. This study is designed to test if asthma management is better if a simple blood test is incorporated into clinical care to provide information to the clinician that prevents unnecessary use of OCS in severe asthma management. One type of airway inflammation (called eosinophilia) has been found to be common in some people who have severe asthma. Clinical studies have shown that these people have a high risk of exacerbation or asthma flare ups even in the presence of high doses of inhaled corticosteroids (ICS). Determining if a person with severe asthma has a high level of eosinophils in their lungs requires the induction of sputum that comes from deep in the airways. This is a lengthy procedure, requires specialist equipment and is not easily carried out in the clinic. Recent research has shown that measuring the number of eosinophils in a blood sample is a substitute for an induced sputum sample and is much simpler. In this study we seek to determine if severe eosinophilic asthma can be managed more effectively using blood eosinophil counts.
Interventions
Participants will attend and be assessed at a total of 14 study clinic visits, which will be at 4 weekly intervals over a 52 week period. In the Inflammation management arm, at each scheduled study visit, adjustment of prednisone oral corticosteroid (OCS) dosage will be performed using the following algorithm based on their fractional of exhaled nitrogen oxide
(FeNO) and blood eosinophil count (cellx109/L). Starting dose of OCS will be dependent on their existing treatment plan.
* Blood eosinop
Participants will attend and be assessed at a total of 14 study clinic visits, which will be at 4 weekly intervals over a 52 week period. In the Inflammation management arm, at each scheduled study visit, adjustment of prednisone oral corticosteroid (OCS) dosage will be performed using the following algorithm based on their fractional of exhaled nitrogen oxide (FeNO) and blood eosinophil count (cellx109/L). Starting dose of OCS will be dependent on their existing treatment plan. * Blood eosinophil count (cellx10 to the 9/L) less than 0.2: Biomarker Score (BS) = -1 * Fractional of exhaled nitrogen oxide (FeNO) less than 15 BS = 0 * FeNO 15 to less than 30 BS = 1 * Blood eosinophil count (cellx10 to the 9/L) 0.2 to 0.4: BS = 1 * FeNO greater than or equal to 30 BS = 2 * Blood eosinophil count (cellx10 to the 9/L) greater than 0.4: BS = 2 The composite BS is calculated from the individual biomarker scores and is the AVERAGE of both scores rounded to the nearest integer to give the "composite score" [score of 0, 1 or 2]. Each participant will be assessed with a BS, and as falling into one of the following 6 categories at their study visit, which will allow their management based on the algorithm. 1. BS = 2, regardless of Asthma Sympton Score (ACQ): increase or (if treatment naïve) commence OCS at 7.5mg/day 2. BS = 1 and ACQ less than or equal to 1.5: no change 3. BS = 1 and ACQ greater than 1.5: no change OCS/inhaled corticosteroids (ICS), increase treatment with GINA (Global Initiative for Asthma)-based symptom algorithm (GBSA) 4. BS = 0 and ACQ less than or eual to 0.75: reduce OCS. If off OCS, decrease treatment with GBSA 5. BS = 0 and ACQ is 0.75 to 1.5: reduce OCS, maintain other treatment 6. BS = 0 and ACQ greater than 1.5: reduce OCS and increase treatment with GBSA If BS = 2 on 50mg/day of OCS, clinician review will take place. See attached Table 1 available on the original ANZCTR record for more details Cut points for FeNO have been decided based on identification of the upper limit of FeNO for asthmatics that can undergo corticosteroid withdrawal, and that which is associated with control of eosinophilic inflammation. Cut points for peripheral blood eosinophils (PBE) have been determined as those previously associated with airway eosinophilia in asthma and COPD. Monitoring of adherence to the drug protocol will be conducted via interview during the study visits as well as returning the drug packet to count unused drugs.
Sponsors
Hunter New England Health
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed severe treatment-resistant asthma (GINA step 4 or higher) with documented evidence of variable airflow limitation or Respiratory consultant diagnosis of asthma) * Never or ex-smoker * Prescribed greater than 1000 micrograms of inhaled beclomethasone (CFC) metered dose inhaler (or equivalent) and inhaled long acting beta-2 agonist (LABA) for at least 6 months * Remain uncontrolled with an asthma control questionnaire (ACQ) score greater than or equal to 1.5 OR Have had a hospital admission for asthma in the last 12 months OR Have experienced at least 2 asthma exacerbations in the past 12 months requiring a course of OCS (at least 3 days).
Exclusion criteria
* Current smoker or smoking cessation within the last 6 months * Severe exacerbation or alteration to asthma therapy within 4 weeks prior to Visit 1 * Eligible for commencing Omalizumab (according to current Pharmaceutical Benefits Scheme criteria), or currently within the first 6 months of commencing Omalizumab. * Other medical comorbidity or research study requiring chronic systemic corticosteroid (for example rheumatologic conditions, adrenal insufficiency, etc.) * Eligible for commencing Mepolizumab or currently within the first 6 weeks of commencing Mepolizumab
Outcome results
None listed