A1021 - Targeted Lung Denervation for Chronic Obstructive Pulmonary Disease: 12-Month Crossover Data from the AIRFLOW-2 Trial
Author Block: F. Conway¹, P. L. Shah², A. Valipour³, D. Slebos⁴, C. Pison⁵, C. Schumann⁶, P. I. Bonta⁷, R. Kessler⁸, W. Gesierich⁹, K. Darwiche¹⁰, B. Lamprecht¹¹, D. Skowasch¹², J. Tonkin²; ¹Imperial College London and Royal Brompton Hospital, London, United Kingdom, ²Royal Brompton Hospital, London, United Kingdom, ³Karl-Landsteiner-Institute for Lung Research, Vienna, Austria, ⁴Pulmonary Diseases, University Medical Center Groningen, Groningen, Netherlands, ⁵Pôle Thorax et Vaisseaux, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France, ⁶Clinic of Pneumology, Thoracic Oncology, Sleep- and Respiratory Critical Care, Klinikverbund Allgaeu, Kempten and Immenstadt, Kempten, Germany, ⁷Academic Medical Center, Amsterdam, Netherlands, ⁸Service de Pneumologie, Nouvel Hôpital Civil, Université de Strasbourg, Strasbourg, France, ⁹Asklepios-Fachkliniken Munich-Gauting, Comprehensive Pneumology Center Munich, Gauting, Germany, ¹⁰Department of Pulmonary Medicine, Section of Interventional Pneumology, Ruhrlandklinik -University Hospital Essen, University of Duisburg-Essen, Essen, Germany, ¹¹Pulmonary Medicine, Kepler University Hospital, Linz, Austria, ¹²Department of Internal Medicine II - Cardiology/Pneumology, University of Bonn, Bonn, Germany.
Rationale:Targeted Lung Denervation (TLD) is a novel therapy being investigated for Chronic Obstructive Pulmonary Disease (COPD). Radiofrequency energy is delivered bronchoscopically to the main bronchi to disrupt the pulmonary parasympathetic nerves and reduce bronchoconstriction and mucus hypersecretion. The objective of this work was to determine the effect of TLD on acute exacerbations of COPD (AECOPD) in crossover subjects in the AIRFLOW-2 trial.
Methods: The AIRFLOW-2 trial is a multicentre, randomised, double-blind, sham-controlled cross-over trial of TLD in patients with COPD. On enrolment to AIRFLOW-2, patients with COPD (modified Medical Research Council dyspnoea scale (mMRC) ≥ 2, COPD Assessment Test (CAT) score ≥ 10) on optimal medical therapy with an FEV₁ 30-60% predicted were randomised to TLD or sham bronchoscopy in a 1:1 ratio. After 12 months, subjects in the sham arm were invited to cross over to the TLD treatment arm. The primary end point was the rate of respiratory adverse events. Secondary end points included all adverse events, changes in lung function and health related quality of life and symptom scores.
Results: Approximately half of the subjects in the sham arm (20 of 41) were eligible and opted to cross over into the TLD arm and were subsequently followed up for 12 months (50% female, mean age 64.1 ± 6.9 years). Comparing the follow up periods after sham bronchoscopy and after crossover for these subjects, there was a trend towards a reduction in time to first AECOPD with a hazard ratio of 0.65, although this was not statistically significant (p = 0.28). There was also a non-statistically significant reduction in time to first severe AECOPD in the crossover period (hazard ratio 0.38, p = 0.227). St George’s Respiratory Questionnaire for COPD score, CAT score and lung function all showed stability over the 12-month period. Safety data was reassuring with no gastrointestinal severe adverse events.
Conclusions:The current study was not powered for a significant effect on AECOPDs, but paired data from the 20 subjects in the crossover cohort of the AIRFLOW-2 trial show a trend for reduction in AECOPDs which supports the 12-month data from the randomisation phase. Furthermore, this crossover data provides additional safety information consistent with the 12-month randomisation data. The AIRFLOW-3 trial is a phase III clinical trial currently underway to further investigate the efficacy of TLD in reducing COPD exacerbations.