None listed
Conditions
Brief summary
The Global Initiative for Asthma (GINA) and various national guidelines have recently recommended the use of Symbicort (a combination inhaled corticosteroid or ICS and long acting beta2 agonist formoterol or FORM) as-needed as an alternative treatment strategy (track-1) for patients with mild asthma. The existing evidence comparing regular ICS plus a short acting beta2 agonist (SABA) as-needed with ICS/FORM as-needed in GINA Step 2 asthma patients, however this data is limited to only four clinical trials. These have consistently demonstrated benefits in favour of regular ICS plus SABA as-needed in terms of symptom control and lung function improvement compared to ICS/FORM as-needed. An open-label study demonstrated a significantly greater reduction in forced exhaled nitric oxide (FeNO) with regular ICS plus SABA as-needed compared to ICS/FORM as-needed despite suboptimal adherence of 56% to twice-daily ICS. This suggests that regular ICS plus SABA as-needed provides more effective attenuation of inflammation compared to ICS/FORM as-needed in patients with mild asthma. To date there is no evidence evaluating the effect of ICS/FORM as-needed on airway hyperresponsiveness (AHR) a key feature of asthma that identifies active asthma. Thus, based on the established understanding of the mechanisms of attenuation of indirect AHR to inhaled mannitol, the hypothesis of this study is that regular ICS plus SABA as-needed suppresses AHR more effectively than ICS/FORM as-needed.
Interventions
A 18-week, randomised, controlled, open-label, parallel-group study in adults with mild asthma; the first 12-weeks evaluating the efficacy and safety of Arnuity® (fluticasone furoate, FF) Ellipta® 100mcg once daily plus Ventolin® (salbutamol) 100mcg as needed (Arm A) and Flixotide® (fluticasone propionate, FP) Junior Accuhaler® (FP) 100mcg twice daily plus Ventolin® (salbutamol) 100mcg as needed (Arm B) compared with Symbicort® (budesonide/formoterol, BUD/FORM) Turbuhaler® 200/6mcg as needed (co
A 18-week, randomised, controlled, open-label, parallel-group study in adults with mild asthma; the first 12-weeks evaluating the efficacy and safety of Arnuity® (fluticasone furoate, FF) Ellipta® 100mcg once daily plus Ventolin® (salbutamol) 100mcg as needed (Arm A) and Flixotide® (fluticasone propionate, FP) Junior Accuhaler® (FP) 100mcg twice daily plus Ventolin® (salbutamol) 100mcg as needed (Arm B) compared with Symbicort® (budesonide/formoterol, BUD/FORM) Turbuhaler® 200/6mcg as needed (comparator)(Arm C). For the last 6 weeks, Arm B will remain the same however from week 12-18, Arm A and C will have their dosage changed to: Arnuity® (fluticasone furoate, FF) Ellipta® 100mcg once every other day (3 doses per week) plus Ventolin® (salbutamol) 100mcg as needed (Arm A) and Pulmicort® (budesonide, BUD) Turbuhaler® 200mcg twice daily plus Ventolin® (salbutamol) 100mcg as needed (Arm C). All these formulations are administered via inhalation. Efficacy will be assessed by assessing improvement in airway hyperresponsiveness using inhaled mannitol (AridolTM), a bronchial provocation test. The outcome for this test is the provoking dose of mannitol to cause a 15% fall in FEV1 (PD15). Adherence to medications throughout the trial will be monitored using electronic adherence monitors (HailieTM).
Sponsors
Dr John D Brannan
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
· Provision of informed consent · Adults 18 years of age or older · Physician diagnosis of asthma as mild disease as per GINA 2021 classification · Symptomatic ACQ5 greater than 0.75 · Pre-bronchodilator FEV1 more than 80% of predicted · AHR to mannitol at screening with a PD15 to mannitol of less than or equal to 155mg · No ICS use for 1 month prior · Willing and able to give informed consent for participation in the trial · In the Investigator’s opinion, able and willing to comply with all trial requirements
Exclusion criteria
· Participation in another clinical study · Any asthma worsening requiring change in asthma treatment other than SABA within 30 days prior to Visit 1 · Use of oral, rectal or parenteral glucocorticosteroids (GCS) within 30 days and/or depot parenteral GCS within 12 weeks prior to Visit 1 · Use of leukotriene receptor antagonists within 30 days prior to Visit 1 · Known or suspected hypersensitivity to study drugs or excipient · Smoker (current or previous) with a smoking history of less than or equal to 10 pack years · Use of any ß-blocking agent including eye-drops · Medical history of life-threatening asthma including intubation and intensive care unit admission · Hospital admission for asthma in the 12 months prior to Visit 1 · Other significant respiratory disease (COPD, bronchiectasis, lung cancer…) · Any significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, or may influence the results of the study, or the patient’s ability to participate in the study · Planned hospital stay · Pregnancy, breast-feeding or planned pregnancy during the study. Fertile women not using acceptable contraceptive measures, as judged by the investigator · Unwilling or unable to switch from current asthma treatment regimen · Not ready to comply with required medication withholding times for Mannitol challenge testing For randomisation at Visit 3, patients should not fulfil any of the following criteria: · Use of 6 or more SABA ‘as needed’ inhalations per day for at least 4 days of run-in · Any asthma worsening requiring change in asthma treatment other than inhaled SABA from Visit 1 until Visit 3 and/or requiring any asthma treatment other than run-in study medication from Visit 2 until randomisation
Outcome results
None listed