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Evaluation of the Safety and Efficacy of TLD in Patients With COPD (AIRFLOW-3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03639051
Recruitment Status : Recruiting
First Posted : August 20, 2018
Last Update Posted : October 5, 2020
Sponsor:
Information provided by (Responsible Party):
Nuvaira, Inc.

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.

Condition or disease Intervention/treatment Phase
COPD Device: Targeted Lung Denervation (TLD) Other: Optimal Medical Care Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 480 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: Double (Participant, Outcomes Assessor)
Masking Description: Subject and assessor double-blinding will be maintained through 1 year post-procedure.
Primary Purpose: Treatment
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)
Actual Study Start Date : May 23, 2019
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : April 2027

Arm Intervention/treatment
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)
Targeted Lung Denervation (TLD) Therapy is a bronchoscopically guided, minimally invasive procedure using the Nuvaira™ Lung Denervation System.
Other Name: TLD, TLD Therapy

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

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




Primary Outcome Measures :
  1. Moderate or severe COPD exacerbations [ Time Frame: Randomization to 12 Months ]
    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).


Secondary Outcome Measures :
  1. Time to first severe COPD exacerbation [ Time Frame: Randomization to 12 Months ]
    Defined as a comparison between study arms of the survival distributions for events based on log-rank tests

  2. Time to first severe COPD exacerbation (Subgroup) [ Time Frame: Randomization to 12 months ]
    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.

  3. Change in St. George's Respiratory Questionnaire COPD Version (SGRQ-C) Total score [ Time Frame: Randomization to 12 months ]

    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).


  4. Change in FVC [ Time Frame: Randomization to 12 Months ]
    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.

  5. Change in FEV1 [ Time Frame: Randomization to 12 months ]
    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.

  6. Transition Dyspnea Index (TDI) [ Time Frame: Randomization to 12 months ]
    Defined as a comparison between study arms of the TDI based on a linear model for change in TDI.

  7. Change in RV [ Time Frame: Randomization to 12 months ]
    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.

  8. Time to first respiratory-related hospitalization [ Time Frame: Randomization to 12 Months ]
    Defined as a comparison between study arms of the survival distributions for events based on log-rank tests.

  9. Change in Short Form Health Survey (SF-36) total score [ Time Frame: Randomization to 12 Months ]

    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.


  10. CAT responders [ Time Frame: Randomization to 12 Months ]

    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.



Other Outcome Measures:
  1. Changes in quality of life [ Time Frame: Randomization to 6, 12 Months ]
    Change in St. George's Respiratory Questionnaire (SGRQ-C), COPD Assessment Test (CAT) and Short Health Survey (SF-36) scores

  2. Adverse event rates [ Time Frame: Randomization to 12 Months, 3 to 12 Months ]
    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

  3. Time to first event [ Time Frame: 3 to 12 Months ]
    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

  4. Changes in lung function [ Time Frame: Randomization to 12 Months ]
    Changes in Forced Expiratory Volume in 1 second (FEV1), Forced Vital Capacity (FVC) and Body plethysmography measures (IC, TLC, RV)

  5. Changes in dyspnea [ Time Frame: Randomization to 12 Months ]
    Changes in dyspnea including Modified Medical Research Council (mMRC) Dyspnea Scale scores and Baseline and Transition Dyspnea Indexes (BDI/TDI) scores

  6. Healthcare utilization [ Time Frame: Randomization to 12 Months ]
    Defined as respiratory-related unscheduled clinic visits, ER visits and hospitalizations



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   40 Years to 78 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject ≥40 and ≤78 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 30%≤ FEV1 ≤60% of predicted 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 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;
  • The subject is willing, able and agrees to complete all protocol required baseline and follow-up testing 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 as evidenced by an HbA1c >7 %;
  • Pulmonary nodule thought to be at high risk of malignancy;
  • Malignancy treated with radiation or chemotherapy within 2 years of consent;
  • Four (4) or more respiratory related hospitalizations 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 which affects the lungs (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 2 years 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;
  • Known pre-existing diagnosis of pulmonary hypertension, defined as clinical evidence of pulmonary hypertension (i.e. cardiovascular function impairment including peripheral edema) and a sustained elevation of the mean pulmonary artery pressure ≥25 mmHg at rest by right heart catheterization or estimated right ventricular systolic pressure >40 mmHg by echocardiogram;
  • Myocardial infarction within last 6 months, EKG with evidence of life threatening arrhythmias or acute ischemia, pre-existing documented evidence of an LVEF <45%, 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;
  • Subjects who have had abdominal surgical procedure(s) on the stomach, esophagus or pancreas performed ≤2 years of consent or have ongoing related symptoms within the past year;
  • Subjects with symptomatic gastric motility disorder(s) (e.g., gastroparesis) as evidenced by a GCSI score ≥18.0 or with severe GERD (e.g., refractory heartburn, endoscopic esophagitis) or severe dysphagia (e.g., esophageal stricture, achalasia, esophageal spasm);
  • The subject has 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, coils, median sternotomy, bullectomy, lobectomy or segmentectomy or other interventional lung procedure performed ≤1 year of consent); NOTE: Segmentectomy for benign lesion or segmentectomy for non-recurrent cancer ≥2 years is allowed. Vascular stents allowed if implanted ≥3 months and ≥5 mm away from the anticipated treatment location(s). Subjects with explanted lung valve(s) allowed if ≥3 months and meet all other enrollment criteria.
  • Daily use of >10 mg of prednisone or its equivalent at the time of consent;
  • Recent (within 3 months of consent) opioid use;
  • 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 site discovery of a mass that requires treatment;
  • Subject is currently enrolled in another interventional clinical trial that has not completed follow-up.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03639051


Contacts
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Contact: Delanie Reller (763) 450-5673 dreller@nuvaira.com

Locations
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Sponsors and Collaborators
Nuvaira, Inc.
Investigators
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Principal Investigator: Frank Sciurba, MD University of Pittsburgh Medical Center
Principal Investigator: Dirk-Jan Slebos, MD, PhD University Medical Center Groningen
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Nuvaira, Inc.
ClinicalTrials.gov Identifier: NCT03639051    
Other Study ID Numbers: D0543
First Posted: August 20, 2018    Key Record Dates
Last Update Posted: October 5, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Supporting Materials: Study Protocol
Statistical Analysis Plan (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).

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Product Manufactured in and Exported from the U.S.: Yes