Ultra-long Acting Bronchodilator Therapy in Smoking Asthmatics

Phase 4

Completed

• Conditions: Asthma
• Interventions: Drug: olodaterol hydrochloride 2.5mcg, tiotropium bromide 2.5mcg; Drug: olodaterol 2.5 mcg

• Registration Number: NCT02682862
• Lead Sponsor: University of Dundee

Brief Summary

Single centre, open-label, random order, cross-over trial, recruited over a period of approximately 2 years. Sufficient participants enrolled to complete 16 adults. Withdrawn subjects may be replaced.

This clinical trial will assess the effects of ultra-long acting bronchodilator therapy in smoking asthmatics taking inhaled corticosteroids. This will be via a pulmonary function test called impulse oscillometry.

Detailed Description

Cigarette smoking in asthma is associated with poorer asthma control and a higher frequency of asthma attacks. Despite this, smoking cessation rates are very low due to the highly addictive nature of tobacco smoking. Asthma in smokers is particularly challenging to manage because it is resistant to the beneficial effects of inhaled corticosteroids, the main treatment for asthma.

Unfortunately, there is no guideline consensus regarding how to best manage asthmatics who smoke. Research studies in asthma tend to exclude smokers because of concerns about recruiting patients with chronic obstructive pulmonary disease (COPD). Hence, there is an unmet need for research studies in asthmatics who are unable to stop smoking.

In view of the above, we propose to assess the effects of two different types of bronchodilators (inhalers which help open up the airways), in asthmatics who continue to smoke.

Participants will receive both of the following drugs for 2-4 weeks in random order, with a 2-3 week washout period in between:

Olodaterol which is a new long-acting bronchodilator. Olodaterol combined with tiotropium (dual bronchodilators). We wish to compare these inhalers using a sensitive pulmonary function test called impulse oscillometry.

Study Timeline

• Study First Submitted: 2016-02-04
• Study First Submitted QC: 2016-02-10
• Study First Posted: 2016-02-17
• Study Start: 2016-07-11
• Primary Completion: 2019-05-22
• Study Completion: 2019-05-22
• Status Verified: 2019-06
• Last Update Submitted: 2019-06-20
• Last Update Posted: 2019-06-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 17

Inclusion Criteria

• Male or female volunteers aged 18-65 years with persistent asthma and on inhaled corticosteroids (at least 400 micrograms beclomethasone dipropionate equivalent dose daily)
• Current smoker
• Forced Expiratory Volume in 1 second (FEV1) ≥ 60 % predicted
• Ability to give informed consent
• Agreement for their General Practitioner to be made aware of study participation and to receive feedback as relevant to the participant's well being

Exclusion Criteria

• Other significant respiratory diseases, in the opinion of the investigator, such as COPD or bronchiectasis.
• An asthma exacerbation or respiratory tract infection requiring systemic steroids and/or antibiotics within 1 month of the study commencement or 3 months if hospital admission was required
• Any clinically significant medical condition that may endanger the health or safety of the participant
• Participation in another drug trial within 30 days before the commencement of the study
• Pregnancy or lactation
• Unable to comply with the procedures of the protocol
• Unable or unwilling to consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Spiolto Respimat	olodaterol hydrochloride 2.5mcg, tiotropium bromide 2.5mcg	olodaterol hydrochloride 2.5mcg, tiotropium bromide 2.5mcg 2 puffs OD (once daily) for 2-4 weeks. Participants then enter washout period and receive alternative treatment arm
Striverdi Respimat	olodaterol 2.5 mcg	olodaterol 2.5mcg 2 puffs OD (once daily) for 2-4 weeks. Participants then enter washout period and receive alternative treatment arm

Primary Outcome Measures

Name	Time	Method
Airway resistance at 5Hz (R5)	2-4 weeks	measured by Impulse oscillometry (IOS)

Secondary Outcome Measures

Name	Time	Method
X5	2-4 weeks	Impulse Oscillometry: Reactance at 5Hz
Mannitol RDR	2-4 weeks	Response-Dose Ratio
R5 at PD30	2-4 weeks	Airway Resistance at 5 Hertz at PD30
Salbutamol recovery time following mannitol challenge	2-4 weeks
Domiciliary PEF	2-4 weeks	Peak Expiratory Flow
ACQ	2-4 weeks	Asthma Control Questionnaire
R5-R20	2-4 weeks	Impulse Oscillometry: Resistance at 5Hz minus Resistance at 20Hz, equating to small airway resistance
FEF25-75 pre and post challenge	2-4 weeks	Spirometry: Forced expiratory flow 25%-75% pre and post bronchial challenge (assessing change)
FVC pre and post challenge	2-4 weeks	Spirometry: Forced vital capacity pre and post bronchial challenge (assessing change)
RF	2-4 weeks	Impulse Oscillometry: Resonant Frequency
AX	2-4 weeks	Impulse Oscillometry: Reactance Area
R20	2-4 weeks	Impulse Oscillometry: Resistance at 20Hz
Mannitol PD30	2-4 weeks	Provocation dose of mannitol causing 30% increase in R5
FEV1 pre and post challenge	2-4 weeks	Spirometry: Forced expiratory volume in 1 second pre and post bronchial challenge (assessing change)

Trial Locations

Locations (1)

Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and Medical School; 🇬🇧 Dundee, Scotland, United Kingdom