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

COPD Clinical Trial

— AIRFLOW-3  

Official title:

A Multicenter, Randomized, Sham-controlled Study to Evaluate Safety and Efficacy After Treatment With the Nuvaira™ Lung Denervation System in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03639051
• Other study ID #: D0543
• Status: Active, not recruiting
• Phase: N/A
• Start date: May 23, 2019
• Est. completion date: September 2028

Study information

• Verified date: September 2023
• Source: Nuvaira, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 464
• Est. completion date: September 2028
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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:

• 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.

Related Conditions & MeSH terms

• COPD

Intervention

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

Other:
• Optimal Medical Care
Taking regular maintenance medication that minimally includes a long-acting muscarinic antagonist (LAMA) and a long-acting beta2-agonist (LABA).

Locations

Country	Name	City	State
Austria	Krankenhaus Nord - Klinik Floridsdorf	Vienna
France	Hopital de la Cavale Blanche	Brest
France	CHU de Grenoble	Grenoble	Cedex 9
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	Hopital Larrey	Toulouse	Cedex 9
Germany	Thorax Klinik Heidelberg	Heidelberg
Netherlands	UMC	Amsterdam
Netherlands	University Medical Center Groningen (UMCG)	Groningen
United Kingdom	Royal Brompton Harefield Trust	London
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Alabama at Birmingham (UAB) Lung Health Center	Birmingham	Alabama
United States	Lahey Hospital & Medical Center	Burlington	Massachusetts
United States	Medical University of South Carolina (MUSC)	Charleston	South Carolina
United States	University of Chicago	Chicago	Illinois
United States	Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Duke University	Durham	North Carolina
United States	Suburban Lung Associates	Elk Grove Village	Illinois
United States	St. Davids HealthCare	Georgetown	Texas
United States	Spectrum Health Medical Group	Grand Rapids	Michigan
United States	Houston Methodist Hospital	Houston	Texas
United States	Ascension St. Vincent's	Jacksonville	Florida
United States	University of Louisville	Louisville	Kentucky
United States	Temple Lung Center	Philadelphia	Pennsylvania
United States	HonorHealth	Phoenix	Arizona
United States	First Health of the Carolinas	Pinehurst	North Carolina
United States	University of Pittsburgh Medical Center (UPMC)	Pittsburgh	Pennsylvania
United States	UC Davis	Sacramento	California
United States	Washington University	Saint Louis	Missouri
United States	Harbor UCLA	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Nuvaira, Inc.

Countries where clinical trial is conducted

United States,  Austria,  France,  Germany,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	Randomization to 6, 12 Months
Other	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	Randomization to 12 Months, 3 to 12 Months
Other	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	3 to 12 Months
Other	Changes in lung function	Changes in Forced Expiratory Volume in 1 second (FEV1), Forced Vital Capacity (FVC) and Body plethysmography measures (IC, TLC, RV)	Randomization to 12 Months
Other	Changes in dyspnea	Changes in dyspnea including Modified Medical Research Council (mMRC) Dyspnea Scale scores and Baseline and Transition Dyspnea Indexes (BDI/TDI) scores	Randomization to 12 Months
Other	Healthcare utilization	Defined as respiratory-related unscheduled clinic visits, ER visits and hospitalizations	Randomization to 12 Months
Primary	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	Time to first severe COPD exacerbation	Defined as a comparison between study arms of the survival distributions for events based on log-rank tests	Randomization to 12 Months
Secondary	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.	Randomization to 12 months
Secondary	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).	Randomization to 12 months
Secondary	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.	Randomization to 12 Months
Secondary	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.	Randomization to 12 months
Secondary	Transition Dyspnea Index (TDI)	Defined as a comparison between study arms of the TDI based on a linear model for change in TDI.	Randomization to 12 months
Secondary	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.	Randomization to 12 months
Secondary	Time to first respiratory-related hospitalization	Defined as a comparison between study arms of the survival distributions for events based on log-rank tests.	Randomization to 12 Months
Secondary	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.	Randomization to 12 Months
Secondary	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.	Randomization to 12 Months