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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 4, 2019
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 evaluate the efficacy of targeted lung denervation (TLD) in addition to optimal medical care to reduce moderate or severe exacerbation's and related hospitalizations, compared with optimal medical care alone, in patients with chronic obstructive pulmonary disease (COPD).

The secondary objective is to evaluate the long-term safety and other efficacy assessments of targeted lung denervation (TLD) in addition to optimal medical care compared with optimal medical care alone.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 520 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 patients on an inhaled corticosteroid will be stratified.
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 : November 2021
Estimated Study Completion Date : December 2025

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: 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: 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: 6, 12 Months ]
    The 36-Item Short Form Health Survey (SF-36) is a generic HRQL; total score ranges from

  10. CAT responders [ Time Frame: 6, 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: 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: 6, 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: 6, 12 Months ]
    Changes in dyspnea including Modified Medical Research Council (mMRC) Dyspnea Scale scores and baseline and Transition Dyspnea Indexes (BDI/TDI) scores

  6. Changes in 6-Minute Walk Test (6 MWT) [ Time Frame: 12 Months ]
    Changes in 6-Minute Walk Test

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

  8. Change in Leicester Cough Questionnaire (LCQ scores) [ Time Frame: 12 Months ]
    Change in Leicester Cough Questionnaire (LCQ scores)

  9. Bode Index [ Time Frame: randomization, 12 months ]
    The BODE Index will be calculated untilizing the BMI, FEV1 (% predicted), mMRC Dyspnea Index Score and 6 MWT distance reported.



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 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient ≥40 and ≤75 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;
  • Non-smoking (e.g., cigarettes, vaping, cannabis, pipes) for a minimum of 2 months prior to consent and agrees to not smoke for the duration of the study;
  • Patient has received a flu vaccination within the 12 months prior to consent and agrees to annual vaccinations for the duration of the study;
  • SpO2 ≥89% on room air at the time of screening;
  • CAT score ≥15 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;
  • Patient has a documented history of having minimally been taking a LAMA and a LABA as regular respiratory maintenance medication for ≥12 months at the time of consent;
  • If patient has participated in pulmonary rehabilitation, program must have been completed ≥3 months prior to consent and patient agrees to continue current level of activity through their 12-month follow-up visit, if applicable;
  • Patient is a candidate for bronchoscopy in the opinion of the physician or per hospital guidelines;
  • The patient is willing, able and agrees to complete all protocol required baseline and follow-up testing assessments including taking certain medications;
  • Patient 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;
  • Patient has an implantable electronic device;
  • Uncontrolled diabetes as evidenced by an HbA1c >7 %;
  • Pulmonary nodule thought to be at high risk of malignancy or a malignancy treated with radiation or chemotherapy within the last 2 years;
  • More than 3 respiratory related hospitalization within 1 year of consent;
  • Documented diagnosis of asthma or failure of asthma screening assessment;
  • Patient has been previously diagnosed with a non-COPD lung disease (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;
  • Clinically relevant bronchiectasis diagnosed by CT whose current treatment would interfere with outcome assessments;
  • Known pre-existing diagnosis of pulmonary hypertension, defined as a sustained elevation of the mean pulmonary artery pressure greater than or equal to 25mm Hg at rest by right heart catheterization or estimated by echocardiogram to be greater than 40 mm Hg;
  • 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 patient an unacceptable candidate for a bronchoscopic procedure utilizing general anesthesia;
  • Known pre-existing gastrointestinal motility disorder (e.g., achalasia, gastroparesis, hiatal hernia, irritable bowel syndrome) or previous abdominal surgical procedure on stomach, esophagus or pancreas (e.g., esophagectomy, gastrostomy, gastrectomy, bariatric surgery, fundoplication, vagotomy);
  • Patients with a GCSI total symptom score ≥18.0 (sum of PAGI-SYM questions 1-9) prior to treatment;
  • The patient 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); NOTE: segmentectomy for benign lesion or segmentectomy for non-recurrent cancer ≥2 years are allowed.
  • Daily use of >10 mg of prednisone or its equivalent at the time of consent;
  • Recent (<3 months ago) 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% (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;
  • In the opinion of the treating investigator, use of the Nuvaira System is not technically feasible due to patient anatomy or other clinical finding (e.g., acute pneumothorax, pleural effusion);
  • Patient is currently enrolled in another 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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United States, Alabama
University of Alabama at Birmingham (UAB) Lung Health Center Recruiting
Birmingham, Alabama, United States, 35294
Contact: Patti Smith    205-996-5392    patriciasmith@uabmc.edu   
Principal Investigator: Mark Dransfield, MD         
United States, Florida
Sarasota Memorial Hospital Recruiting
Sarasota, Florida, United States, 34239
Contact: Heather Barrentine    941-917-3614    Heather-Barrentine@smh.com   
Principal Investigator: Kirk Voelker, MD         
United States, Illinois
Suburban Lung Associates Recruiting
Elk Grove Village, Illinois, United States, 60007
Contact: Lauren Niklinski    224-273-8971    lauren.niklinski@amitahealth.org   
Principal Investigator: Kevin Kovitz, MD         
United States, Massachusetts
Lahey Hospital & Medical Center Recruiting
Burlington, Massachusetts, United States, 01805
Contact: Joyce Pelletier    781-744-3706    joyce.e.pelletier@lahey.org   
Principal Investigator: Carla Lamb, MD         
United States, Ohio
Ohio State University Wexner Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Jamaal Saleh    614-366-2258    jamaal.saleh@osumc.edu   
Principal Investigator: Christian Ghattas, MD         
United States, Pennsylvania
Temple Lung Center Recruiting
Philadelphia, Pennsylvania, United States, 19140
Contact: Helga Criner    215-707-1559    helga.criner@tuhs.temple.edu   
Principal Investigator: Gerard Criner, MD         
University of Pittsburgh Medical Center (UPMC) Recruiting
Pittsburgh, Pennsylvania, United States, 15219
Contact: Jenna Smith       smithjr2@upmc.edu   
Principal Investigator: Frank Sciurba, MD         
United States, South Carolina
Medical University of South Carolina (MUSC) Recruiting
Charleston, South Carolina, United States, 29425
Contact: Mary G Blanton    843-792-3481    blantonm@musc.edu   
Principal Investigator: Charlie Strange, MD         
France
CHU de Grenoble Recruiting
Grenoble, Cedex 9, France, 38043
Contact: Marie Jondot       MJondot@chu-grenoble.fr   
Principal Investigator: Bruno Degano, MD         
Hopital Larrey Recruiting
Toulouse, Cedex 9, France, 31400
Contact: Nicolas Guibert, MD       guibert.n@chu-toulouse.fr   
Netherlands
University Medical Center Groningen (UMCG) Recruiting
Groningen, Netherlands
Contact: Jorine Hartman       j.hartman@umcg.nl   
Principal Investigator: Dirk-Jan Slebos, MD, PhD         
United Kingdom
Royal Brompton Harefield Trust Recruiting
London, United Kingdom
Contact: Francesca Conway, MD       F.Conway@rbht.nhs.uk   
Principal Investigator: Pallav Shah, MD         
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

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Responsible Party: Nuvaira, Inc.
ClinicalTrials.gov Identifier: NCT03639051     History of Changes
Other Study ID Numbers: D0543
First Posted: August 20, 2018    Key Record Dates
Last Update Posted: October 4, 2019
Last Verified: June 2019
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