AIRFLOW-3
Research type
Research Study
Full title
A Multicenter, Randomised, Sham-controlled Study to Evaluate Safety and Efficacy After Treatment with the Nuvaira Lung Denervation System in Subjects with Chronic Obstructive Pulmonary Disease (COPD)
IRAS ID
253708
Contact name
Pallav Shah
Contact email
Clinicaltrials.gov Identifier
Duration of Study in the UK
6 years, 0 months, 1 days
Research summary
Research Summary
Chronic obstructive pulmonary disease (COPD) affects nearly three million people in the UK. It causes debilitating symptoms of breathlessness and exercise intolerance. One of the major causes of these symptoms is the narrowing of the airways within the lungs. This occurs due to inflammation and contraction of the smooth muscle lining the airways. The smooth muscle contraction is controlled by the vagus nerve. Currently we use medications such as tiotropium to help open up the airways by blocking the effect of the vagus nerve. This isn't effective for everyone and means taking inhalers every day. An operation to cut the vagus nerve improves lung function by stopping the nerve from causing contraction of the smooth muscle. However this is not routinely performed as it has significant risks and will affect other organs. The Holaira Targeted Lung Denervation (TLD) system is a minimally invasive way to disconnect the branches of the vagus nerve that only supply the lung. The intention is that by removing the effect of the vagus nerve that there will be a sustained improvement in lung function and symptoms by helping open up narrowed airways. TLD Therapy has the potential to provide long-term sustained improvements in lung function which are similar to the transient peak effectiveness of inhaled drugs such as tiotopium.
So far, there has been 2 pilot studies (IPS-1 and IPS-2) as well as a multi-phase, multi-centre trial (AIRFLOW-1 and AIRFLOW-2). The primary aim of this study is to determine the efficacy of TLD on reducing COPD exacerbations. Previous trials were not designed to measure changes in COPD exacerbation frequency. This trial has been designed with this study outcome in mind. We will also be assessing ongoing safety and efficacy data.
This is a prospective, multi-center, randomized, sham-controlled, double-blind (subject and follow-up assessor(s)), safety and efficacy study.Lay summary of study results
AIRFLOW-3 was a randomized pivotal trial for the dNerva targeted lung denervation
(TLD) system in patients with chronic obstructive pulmonary disease (COPD).Patients were randomized (1:1) to either 1) treatment arm (active TLD treatment + optimal medication treatment) or 2) control arm (sham procedure with no TLD treatment + optimal medication treatment). Both the patient and physicians were blinded to which treatment the patient received through the 1-year follow-up. After the 1-year follow-up, patients in the control arm were given the option to receive the active TLD treatment.
Patients with symptoms of moderate to severe airflow obstruction and at least two moderate or one severe exacerbation during the previous 1 year were enrolled into the study.
The main purpose of this study was to evaluate the impact of TLD (+ optimal medicine treatment) on COPD exacerbations compared with optimal medicine treatment alone. The primary endpoint was a comparison of time to the first moderate or severe COPD exacerbation through 12 months. Secondary endpoints included the rate of severe COPD exacerbations, change in quality of life, change in lung function, and change in COPD Assessment Test score. Total of 388 patients were randomized across 32 clinical sites.
In conclusion, the AIRFLOW-3 failed to meet its primary endpoint for significant reduction in the exacerbation rate between the treatment and control arm. However, analyses of the AIRFLOW-3 results identified a sub-group of patients who may benefit in lung function from the dNerva TLD treatment and a new prospective multicenter randomized controlled trial (AIRFLOW-4) has been initiated to confirm these findings.
REC name
East of England - Cambridge East Research Ethics Committee
REC reference
19/EE/0080
Date of REC Opinion
2 May 2019
REC opinion
Further Information Favourable Opinion