COPDAIRFLOW-4NCT07051707
Evaluating the Safety and Efficacy of dNerva Lung Denervation System in Patients With COPD
A study testing Targeted Lung Denervation (TLD) in people with COPD and Chronic Obstructive Pulmonary Disease, run by Nuvaira, Inc. at 10 sites in United States.
Trial summary
The dNerva Lung Denervation System is one-time treatment intended to improve breathing in Chronic Obstructive Pulmonary Disease (COPD) patients on standard medical care. The purpose of this study is to confirm the safety and efficacy of the Nuvaira Lung Denervation System in the treatment of COPD. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- COPD, Chronic Obstructive Pulmonary Disease
- What is being tested?
- Targeted Lung Denervation (TLD)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 10 sitesUnited States
- Study dates
- 24 Feb 2026to 31 Oct 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 40 and ≤ 80 years of age at the time of consent.
- Women of childbearing 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.
- Resting SpO2 ≥ 89% on room air.
- MMRC ≥ 2; CAT score ≥ 10.
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- Diagnosis of moderate to severe COPD as defined by FEV1/FVC < 70% (post-bronchodilator), 25% ≤ FEV1 ≤ 70% predicted, and PaCO2 < 50 (if FEV1 < 30%).
- RV ≥ 175% of predicted and RV/TLC > 55% (post-bronchodilator).
- Participant is on standard medical care, defined as a minimum of therapy with LABA/ICS, LAMA/LABA, or LAMA/LABA/ICS for at least 2 months prior to 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; NOTE: Prior participation in a pulmonary rehabilitation program is not required for inclusion in the study.
- Participant is a candidate for bronchoscopy in the opinion of the investigator or per hospital guidelines and is able to discontinue blood thinning medication peri-procedurally.
- Participant 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).
Who cannot join
- Body Mass Index (BMI) <18 or >32.
- Participant has an implantable electronic device and has not received appropriate medical clearance.
- Uncontrolled diabetes in the opinion of the investigator.
- 4 or more respiratory related hospitalizations within 1 year of consent.
- Malignancy treated with radiation or chemotherapy within 1 year of consent.
- Participant diagnosed with a dominant non-COPD lung disease, or condition affecting the lungs, which is the main driver of the participant's 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 Asthma) or has a documented medical history of pneumothorax within 1 year of consent.
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- Clinically relevant bronchiectasis, defined as > 1/3 cup mucous expectoration daily.
- 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, evidence of life-threatening arrhythmias or acute ischemia, pre-existing documented evidence of a LVEF < 40%, stage C or D (ACC/AHA) or Class III or IV (NYHA) congestive heart failure.
- 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 GCSI score ≥18.0, severe uncontrolled GERD (e.g., refractory heartburn, endoscopic esophagitis) or severe dysphagia (e.g., esophageal stricture, achalasia, esophageal spasm). NOTE: Participants with a hiatal hernia are allowed if Participant meets all other enrollment criteria.
- 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., BLVR explant procedure, median sternotomy, bullectomy, lobectomy, segmentectomy or other interventional lung or chest procedure) performed ≤1 year of consent? Participants with lung transplant, BLVR valves, LVRS, metal stents within 5cm of the anticipated treatment location; presence of lung volume reduction valves, coils or other lung implants.
- Daily use of >20 mg of prednisone or its equivalent at the time of consent.
- 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 bronchial anatomy cannot be treated with available catheter sizes; presence of whole lung emphysema >20% (-950 HU), single lung emphysema >26% (-950 HU), severe bullous disease (>1/3 hemithorax) or discovery of a mass that requires treatment.
- Participant is currently enrolled in another drug or interventional clinical trial that has not completed follow-up.
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
10 sites in 1 country
United States10 sites, 10 recruiting
- Recruiting
University of Alabama-Birmingham Hospital - UAB Lung Health Center
Birmingham, Alabama, 35233
Daniel Baugh, 205-975-5295, dbaugh@uabmc.edu
Abbey West, 205-934-0590, amwest@uabmc.edu
- Recruiting
Ohio State University Medical Center - Ohio State Lung Center
Columbus, Ohio, 43210
Amy Miller, 614-366-7935, Amy.Miller2@osumc.edu
Michael Woods, 614-366-7935, michael.woods@osumc.edu
- Recruiting
Henry Ford Hospital - Lung and Pulmonary Care
Detroit, Michigan, 48202
Saira Saif, 313-916-2729, ssaif1@hfhs.org
Deepti Naidu, 313-916-2729, dnaidu1@hfhs.org
- Recruiting
Penn Highlands - Lung Innovations/Clinical Research Associates
DuBois, Pennsylvania, 15801
Rebecca Taylor, 814-940-1212, rebecca@clinicalresearchassoc.com
Levi Miller, 814-940-1212, levi@clinicalresearchassoc.com
- Recruiting
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224
John Hazimouratides, 904-953-8995, hatzimouratidesjr.john@mayo.edu
Maria Caruso, 904-953-7897, Caruso.maria@mayo.edu
- Recruiting
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Isabel Gilbert, 414-955-0578, igilbert@mcw.edu
Samantha Servi, 414-955-7030 ext. 904-953-7897, sservi@mcw.edu
- Recruiting
Temple University - Temple Lung Center
Philadelphia, Pennsylvania, 19140
Helga Criner, 215-707-1359, Lii-Yoong.Criner@tuhs.temple.edu
Priya Walia, 215-707-6812, priya.walia@tuhs.temple.edu
- Recruiting
University of Pittsburgh Medical Center - UMPC Comprehensive Lung Center
Pittsburgh, Pennsylvania, 15213
Paula Consolaro, 412-648-6404, consolarpj@upmc.edu
Tiffany Ditter, 412-648-6276, ditterdl2@upmc.edu
- Recruiting
Virginia Commonwealth University Health System
Richmond, Virginia, 23298
Robin Toft, 804-628-4570, robin.toft@vcuhealth.org
Ray (Wes) Shepherd, MD
- Recruiting
Wake Forest School of Medicine
Salem, North Carolina, 27104
Anna Pippins, 336-713-9184, anna.pippins@advocatehealth.org
Jessica Bon, MD
About this study
Official title: A Multicenter, Randomized, Study to Evaluate Safety and Efficacy After Treatment With the dNerva Lung Denervation System in Subjects With Chronic Obstructive Pulmonary Disease (COPD) (AIRFLOW-4)
The dNerva Lung Denervation System is one-time treatment intended to improve breathing in Chronic Obstructive Pulmonary Disease (COPD) patients on standard medical care. The purpose of this study is to confirm the safety and efficacy of the Nuvaira Lung Denervation 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 dNerva Lung Denervation System on top of standard medical care (Treatment arm) compared to standard medical care alone (Control arm) to improve lung function in COPD participants with high RV and low emphysema.
The secondary objective is to compare other efficacy assessments between the Treatment arm and the Control arm, and to confirm the safety profile of lung denervation.
- Conditions
- COPD, Chronic Obstructive Pulmonary Disease
- Being tested
- Targeted Lung Denervation (TLD)
- Keywords
- Optimal Medical Care, Device: dNerva Lung Denervation System, Device: Targeted Lung Denervation (TLD)
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Targeted Lung Denervation (TLD)Device
Also called TLD, TLD Therapy
Targeted Lung Denervation (TLD)Therapy is a bronchoscopically guided minimally invasive one-time treatment using the dNerva Lung Denervation System.
| Study group | Role | What they receive |
|---|---|---|
| Targeted Lung Denervation (TLD) treatment and continue on the same standard COPD medical care | Active comparator | Targeted Lung Denervation (TLD)Therapy is a bronchoscopically guided minimally invasive one-time treatment using the dNerva Lung Denervation System. Patients will also continue taking their standard of care COPD maintenance medication (at minimum LABA/ICS, LAMA/LABA or LABA/LAMA/ICS) that they were on prior to randomization. Receives: Device: Targeted Lung Denervation (TLD) |
| Continue on the same standard COPD medical care | No intervention | Continue taking their same standard of care COPD maintenance medication (at minimum LABA/ICS, LAMA/LABA or LABA/LAMA/ICS) that they were on prior to randomization. |
| Targeted Lung Denervation (TLD) crossover treatment after 1-year follow-up for 'No Intervention' Arm | Other | Participants in 'No Intervention' arm who complete their 1-year follow-up will have the option to receive TLD treatment and will be followed for 1 year after the crossover treatment. Receives: Device: Targeted Lung Denervation (TLD) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint is improvement in FEV1 at 6 months.
FEV1 will be measured through post bronchodilator (Post-BD) force expiratory volume in 1 second (FEV1) test. Change in FEV1 is defined by a comparison between study arms of the mean change in Post-BD FEV1 based on a linear model for change in Post-BD FEV1 from baseline to 6 months follow-up.
Measured: 6 months
Secondary outcomes (5)
Change in Post-BD FEV1
A comparison between study arms of the mean change in Post-BD FEV1 based on a linear model for change in Post-BD FEV1, adjusted for baseline Post-BD FEV1
Measured: 12 months
Change in Post-BD RV
A comparison between study arms of the mean change in Post-BD RV based on a linear model for change in Post-BD RV, adjusted for baseline Post-BD RV
Measured: 12 months
Transition Dyspnea Index (TDI)
A comparison between study arms of the proportion of participants with a ≥1 point increase in TDI
Measured: 12 months
Change in SGRQ-C
A comparison between study arms of proportion of participants with ≥4 point decrease in SGRQ-C total score from baseline
Measured: 12 months
Annualized rate of Moderate and Severe COPD Exacerbations
A comparison between study arms of annualized rate of exacerbations based on log-rank tests
Measured: 91 days to 12 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jul 2025
- Study start24 Feb 2026
- Primary completion30 Apr 2028 (estimated)
- Study completion31 Oct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COPDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized 1:1 into two arms: Targeted Lung Denervation (TLD) therapy plus standard medical care (Treatment) and standard medical care alone (Control). Randomization will be stratified based on investigational site, participation in a pulmonary rehabilitation maintenance program, and baseline single inhaled long acting bronchodilator (LABA-ICS only). Participants randomized to Treatment: will undergo TLD treatment with the dNerva Lung Denervation System while continuing the standard medical care that they were on prior to randomization and followed for 2 years or until study closure, whichever is earlier. Participants randomized to Control: will continue the standard medical care that they were on prior to randomization, followed for 1 year, then given the option to receive TLD treatment. Whether treated or not, participants will continue follow-up for 1 more year or until study closure, whichever is earlier.
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nuvaira, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Temple Health
- Responsible party
- Sponsor
- Investigators
- Prof. Gerard Criner, MD, Principal investigator, Temple Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07051707
- Sponsor's protocol ID
- D0836
- Acronym
- AIRFLOW-4
- Status last verified
- Apr 2026
- First submitted
- 26 Jun 2025
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Study to Evaluate Safety and Efficacy After Treatment With the dNerva Lung Denervation System in Subjects With Chronic Obstructive Pulmonary Disease (COPD) (AIRFLOW-4)
- ClinicalTrials.gov ID
- NCT07051707
- Acronym / sponsor ID
- AIRFLOW-4 / D0836
- Conditions
- COPD, Chronic Obstructive Pulmonary Disease
- Keywords
- Optimal Medical Care, Device: dNerva Lung Denervation System, Device: Targeted Lung Denervation (TLD)
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Nuvaira, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Temple Health
- Study start
- 24 Feb 2026 (actual)
- Primary completion
- 30 Apr 2028 (estimated)
- Study completion
- 31 Oct 2029 (estimated)
- First posted
- 4 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The dNerva Lung Denervation System is one-time treatment intended to improve breathing in Chronic Obstructive Pulmonary Disease (COPD) patients on standard medical care. The purpose of this study is to confirm the safety and efficacy of the Nuvaira Lung Denervation System in the treatment of COPD.
Detailed description
The primary objective of this study is to demonstrate the superiority of treatment with the dNerva Lung Denervation System on top of standard medical care (Treatment arm) compared to standard medical care alone (Control arm) to improve lung function in COPD participants with high RV and low emphysema.
The secondary objective is to compare other efficacy assessments between the Treatment arm and the Control arm, and to confirm the safety profile of lung denervation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Participants will be randomized 1:1 into two arms: Targeted Lung Denervation (TLD) therapy plus standard medical care (Treatment) and standard medical care alone (Control). Randomization will be stratified based on investigational site, participation in a pulmonary rehabilitation maintenance program, and baseline single inhaled long acting bronchodilator (LABA-ICS only). Participants randomized to Treatment: will undergo TLD treatment with the dNerva Lung Denervation System while continuing the standard medical care that they were on prior to randomization and followed for 2 years or until study closure, whichever is earlier. Participants randomized to Control: will continue the standard medical care that they were on prior to randomization, followed for 1 year, then given the option to receive TLD treatment. Whether treated or not, participants will continue follow-up for 1 more year or until study closure, whichever is earlier.
| Arm | Type | Receives |
|---|---|---|
| Targeted Lung Denervation (TLD) treatment and continue on the same standard COPD medical care | Active comparator | Device: Targeted Lung Denervation (TLD)Targeted Lung Denervation (TLD)Therapy is a bronchoscopically guided minimally invasive one-time treatment using the dNerva Lung Denervation System. Patients will also continue taking their standard of care COPD maintenance medication (at minimum LABA/ICS, LAMA/LABA or LABA/LAMA/ICS) that they were on prior to randomization. |
| Continue on the same standard COPD medical care | No intervention | –Continue taking their same standard of care COPD maintenance medication (at minimum LABA/ICS, LAMA/LABA or LABA/LAMA/ICS) that they were on prior to randomization. |
| Targeted Lung Denervation (TLD) crossover treatment after 1-year follow-up for 'No Intervention' Arm | Other | Device: Targeted Lung Denervation (TLD)Participants in 'No Intervention' arm who complete their 1-year follow-up will have the option to receive TLD treatment and will be followed for 1 year after the crossover treatment. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- ≥ 40 and ≤ 80 years of age at the time of consent.
- Women of childbearing 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.
- Resting SpO2 ≥ 89% on room air.
Key exclusion criteria (17 listed)
- Body Mass Index (BMI) <18 or >32.
- Participant has an implantable electronic device and has not received appropriate medical clearance.
- Uncontrolled diabetes in the opinion of the investigator.
- 4 or more respiratory related hospitalizations within 1 year of consent.
- Malignancy treated with radiation or chemotherapy within 1 year of consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Targeted Lung Denervation (TLD)Also: TLD, TLD TherapyTargeted Lung Denervation (TLD)Therapy is a bronchoscopically guided minimally invasive one-time treatment using the dNerva Lung Denervation System. | Device | Targeted Lung Denervation (TLD) crossover treatment after 1-year follow-up for 'No Intervention' Arm, Targeted Lung Denervation (TLD) treatment and continue on the same standard COPD medical care |
Primary outcome
The primary endpoint is improvement in FEV1 at 6 months.
Time frame: 6 months
FEV1 will be measured through post bronchodilator (Post-BD) force expiratory volume in 1 second (FEV1) test. Change in FEV1 is defined by a comparison between study arms of the mean change in Post-BD FEV1 based on a linear model for change in Post-BD FEV1 from baseline to 6 months follow-up.
5 secondary outcomes
Change in Post-BD FEV1
Time frame: 12 months
Change in Post-BD RV
Time frame: 12 months
Transition Dyspnea Index (TDI)
Time frame: 12 months
Change in SGRQ-C
Time frame: 12 months
Annualized rate of Moderate and Severe COPD Exacerbations
Time frame: 91 days to 12 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Prof. Gerard Criner, MD principal investigator
Temple Health
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Targeted Lung Denervation (TLD) in people with COPD and Chronic Obstructive Pulmonary Disease, run by Nuvaira, Inc. at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Elyse Ebeling (763-450-2803, eebeling@nuvaira.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary endpoint is improvement in FEV1 at 6 months. (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.