None listed
Conditions
Brief summary
This study is a feasibility study looking at personalised medicine for asthma. A planned full randomised controlled trial would test whether tailoring a patients treatment according to an algorithm based on their asthma symptoms, level of airway inflammation and airway narrowing gives better results than usual care. Before we can run that full RCT we need to test 5 specific feasibility questions around recruitment, acceptability, and the proportion of participants with co-morbidities which may change how we run it. This open-label single group cohort feasibility study will provide the answers to these five specific questions which may change how we run the full RCT: 1)How quickly can we recruit? 2)Do participants find the intervention acceptable? 3)In theory would participants be willing to take part in a randomised controlled trial testing this approach? 4)What proportion of patients still have not-well controlled asthma at the end of the study, or have had an exacerbation during the study? 5)How common are the additional conditions (e.g. sinus disease) that are looked for at the final visit? Fifty participants will be recruited, 25 in New Zealand and 25 in Australia. Each participant will attend for 3 visits over 10 weeks and will have their medications adjusted according to the treatment algorithm specified in the protocol. All participants will receive inhaled steroid and long-acting bronchodilator medications in line with national and international guidelines. The difference is that the dose of inhaled steroid and whether or not participants are prescribed oral steroids (prednisone) will be adjusted according to the protocol algorithm rather than individual clinician's judgement.
Interventions
Protocolised adjustment of inhaled medication according to blood eosinophil level, exhaled nitric oxide, FEV1:FVC ratio and asthma control test score.
The minimum inhaled medication participants will receive is budesonide/formoterol 200/6mcg one inhalation as needed via the Turbuhaler device. Additional treatment will be given as below:
Corticosteroid dose escalation:
If a participant has evidence of Type 2 inflammation [an inflammatory pathway involving a subpopulation of CD4+ T cells known a
Protocolised adjustment of inhaled medication according to blood eosinophil level, exhaled nitric oxide, FEV1:FVC ratio and asthma control test score. The minimum inhaled medication participants will receive is budesonide/formoterol 200/6mcg one inhalation as needed via the Turbuhaler device. Additional treatment will be given as below: Corticosteroid dose escalation: If a participant has evidence of Type 2 inflammation [an inflammatory pathway involving a subpopulation of CD4+ T cells known as Th2 cells that secrete IL-4, IL-5, and IL-13 and stimulate Type 2 immunity, which is characterized by high IgE antibody titers and eosinophilia] despite this level of treatment their budesonide/formoterol 200/6 will be increased to two inhalations twice daily plus one as-needed. If they still have protocol-defined evidence of Type 2 inflammation despite this level of treatment additional inhaled steroids will be given in the form of budesonide 200mcg turbuhaler two inhalations twice daily. If Type 2 inflammation persists despite this level of treatment oral corticosteroids will be added in the form of oral prednisone tablets 10mg once daily. This dose can be increased if no response to a maximum of oral prednisone tablets 20mg once daily. Bronchodilator medication: If a participant has an FEV1:FVC ratio below the lower limit of normal and they are not already receiving a regular long-acting beta agonist (LABA) the budesonide/formoterol 200/6 will be increased from one inhalation as-needed to two inhalations twice daily plus one as-needed. If the FEV1:FVC ratio remains below the lower limit of normal despite this level of treatment a long-acting muscarinic antagonist will be added in the form of tiotropium respimat 2.5mcg two inhalations once daily. Participants will receive the dispensed medication until the next study visit (6 weeks between visit 1 and visit 2, 4 weeks between visit 2 and visit 3). At the next visit the amount of medication taken will be estimated by means of pill counts for oral medications and by documenting the inhaler dose counter reading for symbicort. Budesonide and tiotropium adherence will not be estimated. At visit 3 there will be an extended assessment protocol in which participants will also complete a number of questionnaires to try and identify co-morbiditites which may be contributing to their symptoms. In this feasibility study these co-morbidities will not be treated as part of the study, but will be treated if clinically appropriate at the conclusion of the study. As this is a feasibility study there is no control group.
Sponsors
Medical Research Institute of New Zealand
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1) Participant is willing and able to give informed consent for participation in the trial. 2) Aged 18 to 75 years on day of enrolment. 3) Self-report of a doctor’s diagnosis of asthma. 4) Asthma not well-controlled, as measured by an ACQ score greater than or equal to 1. 5) Severe asthma exacerbation within the previous year (defined as "a presentation to a general practice, after-hours clinic or emergency department resulting in a prescription for oral corticosteroids or treatment with spacer-delivered or nebulised bronchodilator or self-administration of prednisone for asthma for at least 3 days.") 6) Receiving treatment with an inhaled corticosteroid containing medication for at least 3 months 7) In the Investigator’s opinion, is able and willing to comply with all trial requirements. 8) Willing to allow his or her General Practitioner and consultant, where relevant, to be notified of participation in the trial.
Exclusion criteria
Exclusion criteria: 1) Inhaled corticosteroid dose >1000mcg fluticasone propionate (FP)/day or equivalent. 2) Maintenance oral corticosteroid use for any indication(regular hydrocortisone or fludrocortisone are permitted). 3) Oral corticosteroid use within the previous 4 weeks for any indication (regular hydrocortisone or fludrocortisone are permitted). 4) Under the care of a severe asthma clinic 5)Anti-IgE or anti-IL5 biologics within the previous 4 weeks 6) Current immune suppression or immunodeficiency 7) Previous ICU admission due to asthma 8) Participant who is pregnant, lactating, or planning pregnancy during the course of the trial. 9) Serious co-morbidity liable to affect ability to perform study procedures or interpretation of study results, e.g. recent pneumothorax, interstitial lung disease, bronchiectasis, severe heart failure, myocardial infarction within the last 3 months. 10) Any other significant disease or disorder (including known contraindication to any of the IMPs or excipients) that, in the opinion of the Investigator, may put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial. 11) Participants who have participated in another research trial involving an investigational product in the past 12 weeks.
Outcome results
None listed