Targeted Lung Denervation for Patients With Moderate to Severe COPD (AIRFLOW)

A Sequential Two Phase Multicenter, Randomized Study to Optimize Dose Selection and Evaluate Safety After Treatment With the Holaira™ Lung Denervation System in Patients With Moderate to Severe COPD.

The purpose of this study is to evaluate safety of Targeted Lung Denervation (or TLD) in patients suffering from moderate to severe COPD. It is hypothesized that TLD will have a similar safety profile and improved physiological and functional outcomes to a sham-control.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Device: Holaira™ Lung Denervation System with energy delivery; Device: Holaira™ Lung Denervation System without energy delivery

Detailed Description

A prospective, sequential two phase multicenter, randomized double-blind, safety, & feasibility study. The goal of AIRFLOW-1 will be to compare two energy doses and select the optimal energy dose to be utilized in AIRFLOW-2. The goal of AIRFLOW-2 is to compare the optimal energy dose to a sham control. All subjects will be followed for a minimum of 3 years.

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Linz, Austria
    • AKh Allgemeines Krankenhaus der Stadt Linz GmbH
  • Vienna, Austria, 1140
    • Otto-Wagner-Spital
• Belgium
  • Brussels, Belgium, 1000
    • CHU Saint Pierre
  • Leuven, Belgium, 3000
    • University Hospital Leuven
• France
  • Grenoble, France, 38700
    • CHU de Grenoble
  • Lille, France, 59000
    • CHU de LILLE
  • Paris, France
    • CHU de Paris - Hopital Bichat Claude Bernard
  • Reims, France, 51092
    • CHU de Reims
  • Strasbourg, France, 67000
    • CHU de Strasbourg
• Germany
  • Berlin, Germany, 13353
    • Charite-Universitatsmedizin Berlin
  • Bonn, Germany
    • Universitatklinikum Bonn
  • Essen, Germany, 45239
    • Ruhrlandklinik - West German Lung Center
  • Gauting, Germany, 82131
    • Asklepios-Fachkliniken
  • Heidelberg, Germany, D-69126
    • Thoraxklinik Heidelberg
  • Kempten, Germany, 87509
    • Klinikverbund Kempten-Oberallgaeu
• Netherlands
  • Amsterdam, Netherlands
    • Academic Medical Center
  • The Netherlands
    • Groningen, The Netherlands, Netherlands, 9700
      • Universtity Medical Center Groningen
• United Kingdom
  • London, United Kingdom, SW3,6NY
    • Royal Brompton

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of COPD with 30% ≤ FEV1 < 60% and FEV1/FVC <70% (post-bronchodilator);
• Patient ≥ 40 and ≤ 75 years of age at the time of consent;
• The patient has no child bearing potential or a negative pregnancy test (serum or urine), if applicable;
• Smoking history of at least 10 pack years;
• Non-smoking for a minimum of 2 months prior to consent and agrees to continue not smoking for the duration of the study;
• Participated in a pulmonary rehabilitation program or engaged in regular physical activity under professional supervision in the past 12 months;

Exclusion Criteria:

• Has been less than 6 weeks following the resolution of a COPD exacerbation or active lower respiratory infection (eg. pneumonia);
• History of recurrent respiratory infections and/or COPD exacerbations (more than 2 hospitalizations within 1 year of enrollment);
• Prior lung or chest procedure (eg. lung transplant, LVRS, BLVR, lung implant, metal stent, valves, coils, median sternotomy, bullectomy, segmentectomy, or lobectomy);
• Documented history of asthma diagnosed with onset <30 years of age, cystic fibrosis, paradoxical vocal cord motion, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis, severe interstitial lung disease or active tuberculosis;
• Pulmonary nodule requiring follow-up or intervention unless proven benign;
• Daily use of >10 mg of prednisone or its equivalent at the time of enrollment;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Targeted Lung Denervation; active targeted lung denervation	Device: Holaira™ Lung Denervation System with energy delivery
Sham Comparator: Sham-Control; non-active targeted lung denervation	Device: Holaira™ Lung Denervation System without energy delivery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AIRFLOW-1: Therapeutic interventions through 3 months; AIRFLOW-2: and rate of respiratory adverse events between 3 and 6.5 months	Respiratory adverse events is defined as: worsening bronchitis, worsening dyspnea, common cold, COPD exacerbation, influenza, pneumonia, respiratory infection, respiratory failure, tachypnea and wheezing. Subjects may have reported more than one type of respiratory adverse event.	3-6.5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events over 3 years	The assessment of safety will be based on reporting of adverse events, particularly those adverse events that are respiratory in origin.	3 years
Device Success	Device success is defined as ability to deliver the test device to its intended locations, provide complete circumferential treatment and removal of the test device without the report of an adverse event during the procedure.	6 months
Spirometry measures	Measures include: FEV1, FVC, FEV1/FVC	3 years
Change in Functional testing: Cycle Ergometry & 6MWT		3 years
Heath-related Quality of Life (SGRQ-C & EQ-5D)		3 years
Procedure Success	Procedure Success is defined as device success without the report of an adverse event through hospital discharge.	Through discharge
Plethysmography measures	Measures include Raw, TLC, IC, ITGW	3 years
CT Scan assessment		3 years

Collaborators and Investigators

• Sponsor: Nuvaira, Inc.
• Investigators: Principal Investigator: Dirk-Jan Slebos, MD, University Medical Center Groningen; Principal Investigator: Arschang Valipour, MD, Otto-Wagner-Spital

Publications and helpful links

General Publications

• Valipour A, Shah PL, Herth FJ, Pison C, Schumann C, Hubner RH, Bonta PI, Kessler R, Gesierich W, Darwiche K, Lamprecht B, Perez T, Skowasch D, Deslee G, Marceau A, Sciurba FC, Gosens R, Hartman JE, Conway F, Duller M, Mayse M, Norman HS, Slebos DJ; AIRFLOW-2 Trial Study Group. Two-Year Outcomes for the Double-Blind, Randomized, Sham-Controlled Study of Targeted Lung Denervation in Patients with Moderate to Severe COPD: AIRFLOW-2. Int J Chron Obstruct Pulmon Dis. 2020 Nov 5;15:2807-2816. doi: 10.2147/COPD.S267409. eCollection 2020.
• Slebos DJ, Shah PL, Herth FJF, Pison C, Schumann C, Hubner RH, Bonta PI, Kessler R, Gesierich W, Darwiche K, Lamprecht B, Perez T, Skowasch D, Deslee G, Marceau A, Sciurba FC, Gosens R, Hartman JE, Srikanthan K, Duller M, Valipour A; AIRFLOW-2 Study Group. Safety and Adverse Events after Targeted Lung Denervation for Symptomatic Moderate to Severe Chronic Obstructive Pulmonary Disease (AIRFLOW). A Multicenter Randomized Controlled Clinical Trial. Am J Respir Crit Care Med. 2019 Dec 15;200(12):1477-1486. doi: 10.1164/rccm.201903-0624OC.

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2014
• Primary Completion (Actual): January 26, 2018
• Study Completion (Actual): June 16, 2020

Study Registration Dates

• First Submitted: February 5, 2014
• First Submitted That Met QC Criteria: February 6, 2014
• First Posted (Estimate): February 10, 2014

Study Record Updates

• Last Update Posted (Actual): April 13, 2022
• Last Update Submitted That Met QC Criteria: April 11, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Safety; COPD; Device; Intervention; Lung Function; Targeted Lung Denervation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: AIRFLOW