Evaluation of the Safety and Efficacy of TLD in Patients with COPD

NCT03639051 | Active Not Recruiting DMC FDA Device

• 1 other identifier: D0543
• Study Type: interventional
• Target: 464
• Locations: 6 countries
• Sites: 33

Brief Summary

The purpose of this study is to confirm the safety and efficacy of the Nuvaira Lung Denervation System (Nuvaira System) in the treatment of COPD.

Conditions

COPD

Outcome Measures

Primary Outcomes (1)

• Moderate or severe COPD exacerbations

  A COPD exacerbation will be defined as a complex of respiratory events/symptoms (increase or new onset) of more than one of the following: cough, sputum, wheezing, dyspnea or chest tightness with at least one symptom lasting three days requiring treatment with antibiotics and/or systemic steroids (moderate exacerbation) and/or hospital admission (severe exacerbation).

  Randomization to 12 Months

Secondary Outcomes (10)

• Time to first severe COPD exacerbation

  Randomization to 12 Months

• Time to first severe COPD exacerbation (Subgroup)

  Randomization to 12 months

• Change in St. George's Respiratory Questionnaire COPD Version (SGRQ-C) Total score

  Randomization to 12 months

• Change in FVC

  Randomization to 12 Months

• Change in FEV1

  Randomization to 12 months

Other Outcomes (6)

• Changes in quality of life

  Randomization to 6, 12 Months

• Adverse event rates

  Randomization to 12 Months, 3 to 12 Months

• Time to first event

  3 to 12 Months

Study Arms (2)

Active Treatment

EXPERIMENTAL

Target Lung Denervation (TLD) with the Nuvaira Lung Denervation System (RF energy delivered) and optimal medical care for COPD.

Device: Targeted Lung Denervation (TLD); Other: Optimal Medical Care

Sham Control

SHAM COMPARATOR

Sham Targeted Lung Denervation (TLD) procedure with the Nuvaira Lung Denervation System (catheter placement and balloon deployment in all treatment locations, no RF energy delivered) and optimal medical care for COPD.

Other: Optimal Medical Care

Interventions

Targeted Lung Denervation (TLD) DEVICE

Targeted Lung Denervation (TLD) Therapy is a bronchoscopically guided, minimally invasive procedure using the Nuvaira™ Lung Denervation System.

Also known as: TLD, TLD Therapy

Active Treatment

Optimal Medical Care OTHER

Taking regular maintenance medication that minimally includes a long-acting muscarinic antagonist (LAMA) and a long-acting beta2-agonist (LABA).

Active Treatment; Sham Control

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject ≥40 years of age at the time of consent;
• Women of child bearing potential must not be pregnant, evidenced by a negative pregnancy test (blood or urine) pre-treatment, or lactating and agree not to become pregnant for the duration of the study;
• Smoking history of at least 10 pack years;
• Not smoking or using any other inhaled substance (e.g., cigarettes, vaping, cannabis, pipes) for a minimum of 2 months prior to consent and agrees to not start for the duration of the study;
• Subject has received a flu vaccination within the 12 months prior to the procedure or agrees to obtain vaccination once it becomes available and agrees to annual vaccinations for the duration of the study;
• Resting SpO2 ≥89% on room air at the time of screening;
• CAT score ≥10 at the time of screening;
• Diagnosis of COPD with 25%≤ FEV1 ≤80% of predicted, PaCO2 ˂ 50 (if FEV1 ˂30%) and FEV1/FVC \<70% (post-bronchodilator);
• Documented history of ≥ 2 moderate COPD exacerbations or ≥ 1 severe COPD exacerbation leading to hospitalization in the 12 months prior to consent with at least one exacerbation occurring while the subject was on optimal medical care (taking LAMA and a LABA, or scheduled SABA or SAMA instead of either a LAMA or LABA, not both, as regular respiratory maintenance medication);
• Subject is on optimal medical care at the time of consent;
• If subject has participated in a formal pulmonary rehabilitation program recently, program completion must have occurred ≥3 months prior to consent; if in a maintenance program, subject agrees to continue their current program through their 12-month follow-up visit;
• Subject is a candidate for bronchoscopy in the opinion of the physician or per hospital guidelines and is able to discontinue blood thinning medication peri-procedurally;
• The subject is able and agrees to complete all protocol required baseline and follow-up tests and assessments including taking certain medications (e.g., azithromycin, prednisolone/prednisone);
• Subject has provided written informed consent using a form that has been reviewed and approved by the Institutional Review Board (IRB)/Ethics Committee (EC).

You may not qualify if:

• Body Mass Index \<18 or \>35;
• Subject has an implantable electronic device and has not received appropriate medical clearance;
• Uncontrolled diabetes in the opinion of the investigator;
• Malignancy treated with radiation or chemotherapy within 1 year of consent;
• Asthma as defined by the current Global Initiative for Asthma (GINA) guidelines;
• Subject diagnosed with a dominant non-COPD lung disease or condition affecting the lungs, which is the main driver of the subjects clinical symptoms (e.g., cystic fibrosis, paradoxical vocal cord motion, eosinophilic granulomatosis with polyangiitis (EGPA), allergic bronchopulmonary aspergillosis, interstitial lung disease or active tuberculosis) or has a documented medical history of pneumothorax within 1 year of consent;
• Clinically relevant bronchiectasis, defined as severe single lobe or multilobar broncial wall thickening associated with airway dilation on CT scan leading to cough and tenacious sputum on most days;
• Pre-existing diagnosis of pulmonary hypertension, clinical evidence of pulmonary hypertension (e.g., cardiovascular function impairment including peripheral edema) and mPAP ≥25 mmHg at rest by right heart catheterization (or estimated right ventricular systolic pressure \>50 mmHg by echocardiogram if no previous right heart catheterization);
• Myocardial infarction within last 6 months, EKG with evidence of life threatening arrhythmias or acute ischemia, pre-existing documented evidence of an LVEF \<40%, stage C or D (ACC/AHA) or Class III or IV (NYHA) congestive heart failure, or any other past or present cardiac findings that make the subject an unacceptable candidate for a bronchoscopic procedure utilizing general anesthesia;
• Surgical procedure(s) on the stomach, esophagus or pancreas performed ≤2 years of consent or ongoing related symptoms within the past year;
• Symptomatic gastric motility disorder(s) (e.g., gastroparesis) as evidenced by a GCSI score ≥18.0, severe uncontrolled GERD (e.g., refractory heartburn, endoscopic esophagitis) or severe dysphagia (e.g., esophageal stricture, achalasia, esophageal spasm);
• Any disease or condition that might interfere with completion of a procedure or this study (e.g., structural esophageal disorder, life expectancy \<3 years);
• Prior lung or chest procedure (e.g., lung transplant, LVRS, BLVR, lung implant, metal stent, valves, median sternotomy, bullectomy, lobectomy, segmentectomy or other interventional lung or chest procedure) performed ≤1 year of consent; NOTE: Any metal in the chest must be ≥5 cm away from the anticipated treatment location(s). Subjects with explanted lung valve(s) allowed if explant occurred ≥3 months prior to treatment.
• Daily use of \>10 mg of prednisone or its equivalent at the time of consent;
• Chronic use of \>40 mg MEDD opioid only medication per day;

Sponsors & Collaborators

• Nuvaira, Inc.: lead

Study Sites (33)

University of Alabama at Birmingham (UAB) Lung Health Center

Birmingham, Alabama, 35294, United States

Location

HonorHealth

Phoenix, Arizona, 85258, United States

Location

UC Davis

Sacramento, California, 95817, United States

Location

Harbor UCLA

Torrance, California, 90502, United States

Location

Ascension St. Vincent's

Jacksonville, Florida, 32204, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Suburban Lung Associates

Elk Grove Village, Illinois, 60007, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Lahey Hospital & Medical Center

Burlington, Massachusetts, 01805, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Spectrum Health Medical Group

Grand Rapids, Michigan, 49546, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

First Health of the Carolinas

Pinehurst, North Carolina, 28374, United States

Location

Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Temple Lung Center

Philadelphia, Pennsylvania, 19140, United States

Location

University of Pittsburgh Medical Center (UPMC)

Pittsburgh, Pennsylvania, 15219, United States

Location

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

Location

St. Davids HealthCare

Georgetown, Texas, 78626, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Krankenhaus Nord - Klinik Floridsdorf

Vienna, Austria

Location

CHU de Grenoble

Grenoble, Cedex 9, 38043, France

Location

Hopital Larrey

Toulouse, Cedex 9, 31400, France

Location

Hopital de la Cavale Blanche

Brest, France

Location

Arnaud de Villeneuve Hospital

Montpellier, France

Location

Hopital Pasteur

Nice, France

Location

Bichat-Claude Bernard Hospital

Paris, France

Location

CHU de Reims

Reims, France

Location

CHU de Strasbourg

Strasbourg, France

Location

Thorax Klinik Heidelberg

Heidelberg, Germany

Location

UMC

Amsterdam, Netherlands

Location

University Medical Center Groningen (UMCG)

Groningen, Netherlands

Location

Royal Brompton Harefield Trust

London, United Kingdom

Location

Related Publications (3)

• Shah PL, Slebos DJ, Sue R, Bhatt SP, Ghattas C, Strange C, Degano B, Valipour A, Eisenmann S, De Cardenas J, Marquette CH, Soto-Soto J, Sciurba FC, Conway F, Tonkin J, Tana A, Marchetti N, Hartman JE, Heluain V, Guibert N, Criner GJ. Randomized Sham-controlled Trial of Targeted Lung Denervation in Patients with Chronic Obstructive Pulmonary Disease (AIRFLOW-3). Am J Respir Crit Care Med. 2025 Dec;211(12):2318-2329. doi: 10.1164/rccm.202502-0404OC.

  PMID: 40920914 DERIVED

• Agrawal A. Interventional Pulmonology: Diagnostic and Therapeutic Advances in Bronchoscopy. Am J Ther. 2021 Feb 9;28(2):e204-e216. doi: 10.1097/MJT.0000000000001344.

  PMID: 33590989 DERIVED

• Slebos DJ, Degano B, Valipour A, Shah PL, Deslee G, Sciurba FC; AIRFLOW-3 Trial Study Group. Design for a multicenter, randomized, sham-controlled study to evaluate safety and efficacy after treatment with the Nuvaira(R) lung denervation system in subjects with chronic obstructive pulmonary disease (AIRFLOW-3). BMC Pulm Med. 2020 Feb 13;20(1):41. doi: 10.1186/s12890-020-1058-5.

  PMID: 32054473 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Frank Sciurba, MD

  University of Pittsburgh Medical Center

  PRINCIPAL INVESTIGATOR

• Dirk-Jan Slebos, MD, PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Subject and assessor double-blinding will be maintained through 1 year post-procedure.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be randomized with equal allocation (1:1) into two arms: TLD therapy plus optimal medical care (Active Treatment) and optimal medical care (Sham Control). Randomization of subjects will be stratified based on investigational site, participation in a pulmonary rehabilitation maintenance program and baseline use of an inhaled corticosteroid at the time of enrollment.

Study Record Dates

• First Submitted: August 8, 2018
• First Posted: August 20, 2018
• Study Start: May 23, 2019
• Primary Completion: October 1, 2024
• Study Completion (Estimated): September 1, 2028
• Last Updated: November 14, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Immediately following publication, ending 36 months following article publication.
• Access Criteria: Researchers whose proposed use of the data has been approved by a review committee identified for this purpose will have access to the data required to achieve aims in the approved proposal. Proposals should be directed to pjohnson@nuvaira.com. (Link to be provided).

Locations

AU (1); US (20); FR (8); NL (2); GB (1); DE (1)