Bronchial thermoplasty (BT) for severe asthma in the biologic era: a randomized controlled trial (BOOSTER trial)

For patients with severe asthma that remain uncontrolled with exacerbations
despite biologics or patients who are not eligible for biologics, there is no
reimbursed treatment other than pulmonary rehabilitation in the Netherlands.
Pulmonary rehabilitation is known to have a limited effect for a limited amount
of time. Bronchial thermoplasty or bronchial ablation (BT) is a
non-pharmacological treatment for asthma aiming to restore abnormal airway
function by using an endobronchial approach. Previous RCT*s reported efficacy
on exacerbations and asthma related quality of life (AQLQ), but were performed
before large availability of biologic treatments. Although a single BT
treatment is not without costs, these costs seem to outweigh the costs that can
be saved by the long-term (>5 years) lowering effect of BT on the frequency of
exacerbations and hospitalizations and omitting long term use of trials and
switches of biologics. Therefore, we hypothesize that BT, in the era of
biologics, is superior (in terms of exacerbations and quality of life) over
standard care and cost-effective in patients whose asthma remains uncontrolled
despite optimal anti-inflammatory treatments including biologics, and we
propose to test this hypothesis in a RCT.

To investigate the impact of BT as compared to standard of care in severe
asthma patients that remain uncontrolled despite standard treatment including
adequate doses of inhaled preventer therapies with or without biologics on:
(1) rate of exacerbations
(2) asthma related quality of life (AQLQ)
(3) 1-year and 5-year cost-effectiveness and cost utility

Investigator-initiated randomized, multicenter, parallel-group interventional
RCT of severe asthma patients undergoing either BT (active arm) or standard
care (control arm).

BT (active arm) versus standard care (control arm).

BT efficacy has been demonstrated in previous studies, although with varying
levels of magnitude and across variable populations at the expense of a
relatively small number of expected and manageable adverse events limited to
the initial BT-treatment period. Therefore, we propose that in selected
patients with severe uncontrolled asthma with reduced quality of life and
frequent exacerbations despite optimal (anti-inflammatory) treatment, BT is a
treatment option with high potential in terms of (long term) clinical efficacy
and cost-effectiveness. The patient benefit of study participation is that
he/she is offered a severe asthma treatment that is proven effective and safe
with potential lifelong benefit but unfortunately not regularly available yet.
Patients will be randomized to an active group who receives the BT treatment
and a standard of care group. The total duration of the study, including
follow-up is approximately 15 months. In the active BT treatment group,
patients undergo a total of three bronchoscopies with 3 weeks in between.
First, the right lower lobe is treated, followed by the left lower lobe and
during the last session both upper lobes are treated. The bronchoscopies will
be performed under tailored sedation ranging from conscious sedation (eg
midazolam or propofol) to deep sedation/general anaesthesia to minimize patient
discomfort. Previous experiences in bronchoscopies and BT treatment in severe
asthma patients by our group and other have proven to be safe. Patients will be
treated with prednisolone three days before the procedure, on the day itself
and one day thereafter. During the *treatment period*, patients are offered
one-night hospital stay directly after BT for clinical observation and
exacerbations or transient increase in respiratory symptoms will be treated
with steroids, if considered necessary by the attending pulmonologists. The
*treatment period* ends six weeks after the final (third) BT-procedure is and
the (post-treatment) *follow-up period* starts that will last 12 months. After
this treatment period and during the *follow-up period*, study visits (either
physical or by phone) at 3, 6, 9 and 12 months will be performed, and more
often if deemed necessary due to disease activity or to monitor treatment
changes. The following assessments will be completed: ACQ, AQLQ, EQ-5D-5, PCQ,
SAQ, and monitoring of exacerbations/hospitalizations/ emergency department
visitis, asthma medications, adverse events and lung function (spirometry) and
biomarkers (FeNO and blood eosinophils) at 6 and 12 months. In line with GINA
and NVALT guidelines on severe asthma, it is allowed to initiate additional
treatments, such as initiation of new biologic treatment or referral for
pulmonary rehabilitation.