Design for a multicenter, randomized, sham-controlled study to evaluate safety and efficacy after treatment with the Nuvaira® lung denervation system in subjects with chronic obstructive pulmonary disease (AIRFLOW-3)

Abstract

Background: Targeted lung denervation (TLD) is a bronchoscopically delivered ablation therapy that selectively interrupts pulmonary parasympathetic nerve signaling. The procedure has the potential to alter airway smooth muscle tone and reactivity, decrease mucous secretion, and reduce airway inflammation and reflex airway hyperresponsiveness. Secondary outcome analysis of a previous randomized, sham-controlled trial showed a reduction in moderate-to-severe exacerbations in patients with COPD after TLD treatment. A pivotal trial, AIRFLOW-3 has been designed to evaluate the safety and efficacy of TLD combined with optimal medical therapy to reduce moderate or severe exacerbations throughout 1 year, compared with optimal medical therapy alone. Methods: The study design is a multicenter, randomized, full sham bronchoscopy controlled, double-blind trial that will enroll 400 patients (1:1 randomization). Key inclusion criteria are FEV 1 /FVC < 0.7, FEV 1 30 to 60% of predicted, post-bronchodilator, ≥ 2 moderate or 1 severe COPD exacerbations in the prior year, and COPD assessment test (CAT) ≥ 10. Primary objective will be the comparison of moderate or severe COPD exacerbations through 12 months of TLD therapy with optimal medical therapy versus optimal medical therapy alone. The sham group will be allowed to cross over at 1 year. Patients will be followed for up to 5 years. Discussion: The multicenter, randomized, full sham bronchoscopy controlled, double-blind AIRFLOW-3 trial will evaluate the efficacy of TLD to reduce moderate or severe COPD exacerbations beyond optimal medical therapy alone. The target population are patients with COPD, who suffer persistent symptoms and exacerbations despite optimal treatment, defining an unmet medical need requiring novel therapeutic solutions. This trial is registered at clinicaltrials.gov: NCT03639051.

WITHDRAWN: Safety of Denervation Following Targeted Lung Denervation Therapy for COPD: AIRFLOW-1 Three-year Outcomes

“…The absence of decline three years post-treatment compared with baseline supports stability for lung function and quality of life in this study and both are consistent with the stable rate of exacerbations observed in this study [24]. These observations will need to be con rmed in an ongoing large scale sham-controlled randomized trial (AIRFLOW-3) comparing the e cacy of TLD plus optimal medical care for patients with moderate-to-severe COPD against optimal medical care for COPD [25].…”

Rate of lung function decline slows in the 3 years after targeted lung denervation in COPD

“…Furthermore, a control group is lacking with information on the actual decline in lung function over time in this specific patient group. Currently a large clinical trial with 5 year follow up is underway (Airflow-3, NCT03639051) [4] which has the potential to confirm our results.…”

Safety of denervation following targeted lung denervation therapy for COPD: AIRFLOW-1 3-year outcomes

“…The absence of decline three years post-treatment compared with baseline supports stability for lung function and quality of life in this study and both are consistent with the stable rate of exacerbations observed in this study [ 24 ]. These observations will need to be confirmed in an ongoing large scale sham-controlled randomized trial (AIRFLOW-3) comparing the efficacy of TLD plus optimal medical care for patients with moderate-to-severe COPD against optimal medical care for COPD [ 25 ].…”