Clinical trial NCT03893370: RejuvenAir® System Trial for COPD With Chronic Bronchitis
Official title: A Sham Controlled Prospective Randomized Clinical Trial of the RejuvenAir® System for the Treatment of Moderate to Severe Chronic Obstructive Pulmonary Disease With Chronic Bronchitis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Chronic Bronchitis
Lead sponsor: CSA Medical, Inc.
Sponsor class: INDUSTRY
First posted: 2019-03-28
Enrollment: 210
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: randomized, sham-controlled
Primary purpose: TREATMENT

Brief summary: Chronic Obstructive Pulmonary Disease (COPD) is defined as an impaired ability to move air within the lungs and is a major public health problem that is projected to rank fifth worldwide in terms of disease burden and third in terms of mortality. Chronic bronchitis (CB) is a common clinical phenotype within the umbrella of a COPD diagnosis and is classically defined as chronic cough and sputum production for 3 months a year for 2 consecutive years2, but many studies have used different definitions to define it- chronic cough and sputum production for one year or cough and sputum production on most days of the week. CB is associated with multiple clinical consequences, including; the worsening of lung function decline, increasing risk of acute exacerbations of COPD, increased risk of developing pneumonia, reduced health related quality of life, and an increase in all-cause mortality.

Detailed description: The RejuvenAir® System is a cryosurgical device that applies medical-grade liquid nitrogen to the treatment area via a radial head catheter in a small, accurately directed spray. Cryotherapy with the RejuvenAir® System is designed to induce a regenerative endobronchial tissue effect by: 1) destroying via cryotherapy the abnormal surface epithelium that has become overgrown with mucin producing goblet cells, 2) thus allowing normal bronchial epithelium with a regrowth of ciliated epithelial cells that will facilitate the removal of mucins from the bronchial airways and 3) lead to a reduction in chronic inflammation and its accompanying mucosal swelling with resultant increase in the treated airway diameter. This reversal of inflamed epithelium may also lessen systemic inflammation.

Eligibility criteria: Inclusion Criteria

* Males and females ≥40 to ≤80 years of age
* Subject is able to read, understand, and sign a written Informed Consent in order to participate in the Study
* Subject has a diagnosis of chronic bronchitis (CB) and/or chronic obstructive pulmonary disease (COPD) for a minimum of two years. (Chronic Bronchitis is defined clinically as chronic productive cough for 3 months in each of 2 successive years in a patient in whom other causes of productive cough have been excluded)
* Subject is classified as having a moderate or severe (GOLD 2/3) airflow obstruction defined by a post-bronchodilator of ≥30% FEV1 to \<80% predicted with a baseline FEV1/FVC of \<0.70
* Subject has a Baseline SGRQ of ≥50
* Subject demonstrates daily cough and significant mucus.
* Subject is being treated according to current medically accepted treatment guidelines for chronic bronchitis for minimum of 3 months prior to enrollment into the study. Subject agrees to continue maintenance pulmonary/COPD medications (GOLD standard medications recommended) for the duration of the study
* Non-smoking for a minimum of 2 months prior to consent and agrees to continue not smoking for the duration of the study
* Subject is able to adhere to and undergo 2 bronchoscopic procedures (cross over subjects may undergo two additional bronchoscopic procedures, if they agree to treatment), per hospital guidelines
* Subject demonstrates ability and willingness to use a daily eDiary

Exclusion Criteria

* Subject has had an acute pulmonary infection, exacerbation or pneumonia requiring medical treatment (with antibiotics and/or steroids) within 4 weeks prior of initially planned study bronchoscopy
* Current diagnosis of Asthma
* Subject has Alpha-1 antitrypsin deficiency as defined by blood level \<59 mg/dL
* Subject has other origins of respiratory disease aside from chronic bronchitis and COPD
* Subject is using e-cigarettes, vaping or taking any inhaled substances not prescribed by a physician
* Subject has untreatable or life threatening arrhythmias, inability to adequately oxygenate during the bronchoscopy, or has acute respiratory failure
* Subject has bullous emphysema characterized as large bullae \>30 millimeters on HRCT; or subject has stenosis in the tracheobronchial system, tracheobronchomegaly, trachea-bronchomalacia, amyloidosis or cystic fibrosis
* Subject has clinically significant bronchiectasis
* Subject has had a solid transplant procedure
* Subject has a known mucosal tear, has undergone prior lung surgery such as pneumonectomy, lobectomy, bullectomy, or lung volume reduction surgery
* Subject has had a prior lung device procedure, including emphysema stent(s) implanted, lung coils, valves, lung denervation, bronchial thermoplasty, cryotherapy or other therapies
* Subject is unable to temporarily discontinue use of anticoagulant therapy: warfarin, Coumadin, LMWH, heparin, clopidrogel (or equal)
* Subject has a serious medical condition, such as: uncontrolled coagulopathy or bleeding disorder, congestive heart failure, uncontrolled angina, myocardial infarction in the past year, renal failure, liver disease, cerebrovascular accident within the past 6 months, uncontrolled diabetes, uncontrolled hypertension or uncontrolled gastric reflux
* Subject is pregnant, nursing, or planning to get pregnant during study duration
* Subject has or is receiving chemotherapy or active radiation therapy within the past 6 months or is expected to receive chemotherapy during participation in this study
* Subject is or has been in another treatment study within 6 weeks of enrollment and agrees to not participate in any other treatment studies for the duration of study participation
* Subject has known sensitivity to medication required to perform bronchoscopy (such as lidocaine, atropine, and benzodiazepines)

Primary outcomes:
measure: St. George's Respiratory Questionnaire
timeFrame: 12 months
Secondary outcomes:
measure: Subjects experiencing serious adverse events (SAEs) rated as probably or definitely related to the study device or procedure
timeFrame: Within 30 days after either the first or second study procedure
measure: Reduction of cough
timeFrame: Baseline through 12 months
measure: Reduction of sputum
timeFrame: Baseline through 12 months
measure: Acute Exacerbation Rate (AECOPD)
timeFrame: 12 months
measure: COPD assessment test (CAT) score
timeFrame: 12 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Honor Health
state: Arizona
city: Mountain View
country: United States
facility: El Camino Hospital
state: California
city: Sacramento
country: United States
facility: University of California, Davis Medical Center
state: California
city: Loxahatchee Groves
country: United States
facility: Advanced Pulmonary Research Institute
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Shreveport
country: United States
facility: Louisiana State University Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Universtiy
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Camden
country: United States
facility: Cooper Health System
state: New Jersey
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: University Of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: The Ohio State Universisty
state: Ohio
city: Altoona
country: United States
facility: Clinical Research Associates of Central PA
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University - Of the Commonwealth System of Higher Education
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Columbia
country: United States
facility: Prisma Health - Midlands
state: South Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Georgetown
country: United States
facility: St. David's Georgetown Hospital
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: London
country: United Kingdom
facility: The Royal Brompton Hospital
Study officials:
affiliation: Temple University Health System
name: Gerard Criner, MD
role: PRINCIPAL_INVESTIGATOR
References: