Microbiome Use to Stratify Use of Inhaled Corticosteroids: MUSIC Trial
Status:
Completed
Trial end date:
2019-07-22
Target enrollment:
Participant gender:
Summary
A randomised controlled trial to test the hypothesis that inhaled therapies for chronic
obstructive pulmonary disease (COPD) have differential effects on the upper airway
microbiome.
COPD is the third leading cause of death worldwide. Exacerbations drive disease progression
and worsening quality of life and therefore prevention of exacerbations has been a major goal
of treatment.
Patients with COPD are frequently prescribed inhaled corticosteroids (ICS) which have been
shown to reduce exacerbations in combination with long acting beta2-adrenoceptor agonists
(LABA). In recent years, all ICS preparations have been associated with a significant
increased risk of pneumonia in either randomised trials or observational studies leading to
warnings from national regulatory authorities and leading experts. This has led to a
re-evaluation of the role of ICS in COPD treatments. It is likely that the risk of pneumonia
is not equal across all ICS doses and molecules.
There is a compelling rationale for ICS having a strong effect on the upper airway
microbiome, and that this may be one mechanism of increased pneumonia risk with these drugs.
The existing literature regarding ICS and pneumonia risk are lacking; 1) there are no head to
head trials comparing different ICS preparations and 2) the comparator in these studies to
date have been long acting beta2-adrenoceptor agonists alone, whereas the most appropriate
comparator in current management would be combined LABA and long-acting muscarinic antagonist
(LAMA).
The MUSIC TRIAL is a multi-centre randomised open label controlled parallel group study with
four treatment arms and a total of 120 participants. Severe COPD patients currently treated
with inhaled corticosteroid therapy will be randomised to treatment with one of three
preparations of ICS in combination with LABA or the control arm of dual bronchodilator
therapy following a four week washout period. Participants will return monthly to determine
if there are changes in the microbiome in their upper airway.
This study will establish one potential mechanism for the increased susceptibility to
pneumonia in ICS users and assess intraclass differences in ICS molecules and the effect of
ICS dose on the microbiome. Demonstrating that different COPD treatments can have different
effects on the lung microbiome is an important step in understanding clinical differences in
the safety and effectiveness of different treatments for severe COPD.
Phase:
Phase 4
Details
Lead Sponsor:
University of Dundee
Collaborators:
AstraZeneca NHS Tayside
Treatments:
Bromides Budesonide Budesonide, Formoterol Fumarate Drug Combination Fluticasone Fluticasone Propionate, Salmeterol Xinafoate Drug Combination Fluticasone-Salmeterol Drug Combination Formoterol Fumarate Salmeterol Xinafoate Xhance