Active, not recruitingNCT03639051AIRFLOW-3Updated Nov 14, 2024

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

An interventional study of Targeted Lung Denervation (TLD) and Optimal Medical Care in COPD, sponsored by Nuvaira, Inc.. Active, not recruiting at 33 sites in 6 countries. Open to participants aged 40 Years and older. Per ClinicalTrials.gov, last updated 2024-11-14.

Sponsored by Nuvaira, Inc. · Not applicable, Interventional, and Treatment

Phase: Not applicable
Study type: Interventional
Enrollment: 464
Allocation: Randomized
Ages: 40 Years and older
Sex: All

Study 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.

Read the detailed description

The primary objective of this study is to demonstrate the superiority of treatment with the Nuvaira Lung Denervation System (Active Treatment arm) compared to a sham procedure (Sham Control arm) to decrease moderate or severe exacerbations in subjects with COPD on optimal medical care.

The secondary objective is to compare long-term safety, and other efficacy assessments between the Active Treatment arm and the Sham Control arm.

Conditions studied

COPD

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Pulmonary Disease, Chronic Obstructive 4,253

In context

Pulmonary Disease, Chronic Obstructive

4,253 studies on the registry are indexed under Pulmonary Disease, Chronic Obstructive; 707 are open to participants now.

This study's enrollment of 464 is above the median of 70 across 3,008 interventional studies indexed under Pulmonary Disease, Chronic Obstructive.

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Lead sponsor

Nuvaira, Inc. is the lead sponsor of 7 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 40 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

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).

Exclusion criteria

Exclusion Criteria:

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;
Known contraindication or allergy to medications required for bronchoscopy or general anesthesia (e.g., lidocaine, atropine, propofol, sevoflurane) that cannot be medically controlled;
Baseline chest CT scan reveals bronchi anatomy cannot be fully treated with available catheter sizes, presence of severe emphysema >50%, lobar attenuation area or severe bullous disease (>1/3 hemithorax) (as determined by the CT core lab using a single density mask threshold of -950 HU) or discovery of a mass that requires treatment;
Subject is currently enrolled in another interventional clinical trial that has not completed follow-up.

Study design

Phase: Not applicable
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Outcomes assessor)
Enrollment: 464 participants (actual)

Study arms

Experimental
Active Treatment
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 comparator
Sham Control
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

DeviceTargeted Lung Denervation (TLD)
Targeted Lung Denervation (TLD) Therapy is a bronchoscopically guided, minimally invasive procedure using the Nuvaira™ Lung Denervation System.
Also known as: TLD, TLD Therapy
OtherOptimal Medical Care
Taking regular maintenance medication that minimally includes a long-acting muscarinic antagonist (LAMA) and a long-acting beta2-agonist (LABA).

What researchers measure

Primary outcomes

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).
Time frame: Randomization to 12 Months

Secondary outcomes

Time to first severe COPD exacerbation
Defined as a comparison between study arms of the survival distributions for events based on log-rank tests
Time frame: Randomization to 12 Months
Time to first severe COPD exacerbation (Subgroup)
Defined as a comparison between study arms of the survival distributions for events based on log-rank tests, only for the subgroup of subjects who had a severe COPD exacerbation in the year prior to randomization.
Time frame: Randomization to 12 months
Change in St. George's Respiratory Questionnaire COPD Version (SGRQ-C) Total score
Defined as a comparison between study arms of the mean change in FVC based on a linear model for change in SGRQ-C, adjusted for baseline SGRQ-C. The SGRQ-C is a disease-specific HRQL questionnaire with a total and three component scores for: symptoms, activity and impacts; each score ranges from 0 (no impairment) to 100 (worst possible). A difference in four units in the SGRQ-C score is considered the minimum clinically important difference (MCID).
Time frame: Randomization to 12 months
Change in FVC
Defined as a comparision between study arms of the mean change in FVC based on a linear model for change in FVC, adjusted for baseline FVC.
Time frame: Randomization to 12 Months
Change in FEV1
Defined as a comparison between study arms of the mean change in FEV1 based on a linear model for change in FEV1, adjusted for baseline FEV1.
Time frame: Randomization to 12 months
Transition Dyspnea Index (TDI)
Defined as a comparison between study arms of the TDI based on a linear model for change in TDI.
Time frame: Randomization to 12 months
Change in RV
Defined as a comparison between study arms of the mean change in RV based on a linear model for change in RV, adjusted for baseline RV.
Time frame: Randomization to 12 months
Time to first respiratory-related hospitalization
Defined as a comparison between study arms of the survival distributions for events based on log-rank tests.
Time frame: Randomization to 12 Months
Change in Short Form Health Survey (SF-36) total score
Defined as a comparison between study arms of the mean change in SF-36 total score based on a linear model for change in SF-36 total score, adjusted for baseline SF-36 total score. SF-36 is composed of eight multi-item scales (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, Mental Health), with scores for each of these scales (or dimensions) ranging from 0 to 100. Higher scores indicate higher HRQoL.
Time frame: Randomization to 12 Months
CAT responders
Defined as a comparison between study arms of the proportion of subjects with a greater than or equal to 2 point decrease in CAT. The CAT is a disease-specific HRQL with eight questions; each score ranges from 0 (no impairment) to 5 (worst possible). The CAT has a scoring range of 0-40. Higher scores denote a more severe impact of COPD on a patient's life. A difference in 2 units in the CAT score over 2 to 3 months suggests a clinically significant difference or change in health status.
Time frame: Randomization to 12 Months

Other outcomes

Changes in quality of life
Change in St. George's Respiratory Questionnaire (SGRQ-C), COPD Assessment Test (CAT) and Short Health Survey (SF-36) scores
Time frame: Randomization to 6, 12 Months
Adverse event rates
Defined as the total number of events per total number of treatment years including moderate or severe COPD exacerbations, severe COPD exacerbations, respiratory-related hospitalizations, and lower respiratory-related adverse events
Time frame: Randomization to 12 Months, 3 to 12 Months
Time to first event
Defined as comparison between study arms of the survival distributions for events based on log-rank tests including moderate or severe COPD exacerbations, severe exacerbations and respiratory-related hospitalizations
Time frame: 3 to 12 Months
Changes in lung function
Changes in Forced Expiratory Volume in 1 second (FEV1), Forced Vital Capacity (FVC) and Body plethysmography measures (IC, TLC, RV)
Time frame: Randomization to 12 Months
Changes in dyspnea
Changes in dyspnea including Modified Medical Research Council (mMRC) Dyspnea Scale scores and Baseline and Transition Dyspnea Indexes (BDI/TDI) scores
Time frame: Randomization to 12 Months
Healthcare utilization
Defined as respiratory-related unscheduled clinic visits, ER visits and hospitalizations
Time frame: Randomization to 12 Months

Study locations

33 sites

University of Alabama at Birmingham (UAB) Lung Health Center
Birmingham, Alabama 35294, United States
HonorHealth
Phoenix, Arizona 85258, United States
UC Davis
Sacramento, California 95817, United States
Harbor UCLA
Torrance, California 90502, United States
Ascension St. Vincent's
Jacksonville, Florida 32204, United States
University of Chicago
Chicago, Illinois 60637, United States
Suburban Lung Associates
Elk Grove Village, Illinois 60007, United States
University of Louisville
Louisville, Kentucky 40202, United States
Lahey Hospital & Medical Center
Burlington, Massachusetts 01805, United States
University of Michigan
Ann Arbor, Michigan 48109, United States
Spectrum Health Medical Group
Grand Rapids, Michigan 49546, United States
Washington University
St Louis, Missouri 63110, United States
Duke University
Durham, North Carolina 27710, United States
First Health of the Carolinas
Pinehurst, North Carolina 28374, United States
Ohio State University Wexner Medical Center
Columbus, Ohio 43210, United States
Temple Lung Center
Philadelphia, Pennsylvania 19140, United States
University of Pittsburgh Medical Center (UPMC)
Pittsburgh, Pennsylvania 15219, United States
Medical University of South Carolina (MUSC)
Charleston, South Carolina 29425, United States
St. Davids HealthCare
Georgetown, Texas 78626, United States
Houston Methodist Hospital
Houston, Texas 77030, United States
Krankenhaus Nord - Klinik Floridsdorf
Vienna, Austria
CHU de Grenoble
Grenoble, Cedex 9 38043, France
Hopital Larrey
Toulouse, Cedex 9 31400, France
Hopital de la Cavale Blanche
Brest, France
Arnaud de Villeneuve Hospital
Montpellier, France
Hopital Pasteur
Nice, France
Bichat-Claude Bernard Hospital
Paris, France
CHU de Reims
Reims, France
CHU de Strasbourg
Strasbourg, France
Thorax Klinik Heidelberg
Heidelberg, Germany
UMC
Amsterdam, Netherlands
University Medical Center Groningen (UMCG)
Groningen, Netherlands
Royal Brompton Harefield Trust
London, United Kingdom

References and documents

Publications

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. PubMed 40920914 ↗
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. PubMed 33590989 ↗
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. PubMed 32054473 ↗

Individual participant data

Plan to share: Yes — Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).

Supporting information: Study protocol, Statistical analysis plan, 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).

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Nov 14, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03639051
Lead sponsor: Nuvaira, Inc.
Responsible party: Sponsor
First posted: Aug 20, 2018
Start date: May 23, 2019
Primary completion: Oct 1, 2024
Completion: Sep 2028 (estimated)
Last update: Nov 14, 2024

Study contacts

Frank Sciurba, MD

principal investigator · University of Pittsburgh Medical Center

Dirk-Jan Slebos, MD, PhD

principal investigator · University Medical Center Groningen

Oversight

Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: Yes

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Nov 2024. You cannot join it, but the record below documents what was studied.

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