Safety and Feasibility Study of Rejuvenair™ for Treating Chronic Bronchitis Patients (Feasibility)

• ClinicalTrials.gov Identifier: NCT02483637
• Recruitment Status: Active, not recruiting
• First Posted: June 29, 2015
• Last Update Posted: November 25, 2019
• Sponsor: CSA Medical, Inc.
• Information provided by (Responsible Party): CSA Medical, Inc.

Study Description

Brief Summary:

This study evaluates the safety of RejuvenAir Cryospray therapy to treat symptomatic chronic bronchitis patients with airflow restrictions.

Condition or disease	Intervention/treatment	Phase
Bronchitis, Chronic; Cryotherapy Effect	Device: RejuvenAir	Not Applicable

Detailed Description:

Prospective, open label, single arm study with sequential accrual of subjects with known chronic bronchitis. There are two phases to this study. Phase A will enroll up to 12 subjects and will treat a single lobe to assess safety, feasibility and histology/immunology. After review of the data by the Data Safety Monitoring Board, Phase B of the study would begin. In Phase B of the study, Phase A subjects would have their remaining two lobes treated. In addition up to 24 subjects will be enrolled and will have all upper and lower lobes treated to assess safety, feasibility and immunology.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Intervention Model: Single Group Assignment
• Intervention Model Description: RejuvenAir
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective Safety and Feasibility Study of the RejuvenAir™ System Metered Cryospray Therapy for Chronic Bronchitis Patients
• Study Start Date: February 2016
• Actual Primary Completion Date: May 2019
• Estimated Study Completion Date: September 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: RejuvenAir; RejuvenAir treatment of the right lower lobe and right main stem bronchus. Each MCS will be tailored to the bronchial area undergoing treatment and the amount of liquid nitrogen delivered will vary depending on the airway diameter.	Device: RejuvenAir; Device: RejuvenAir

Outcome Measures

Primary Outcome Measures :

1. Adverse and Serious Adverse Events [ Time Frame: Change from Baseline to 3-Months Following Completion of Treatments ]
   Number of subjects with treatment emergent adverse events. Observed rates and two-sided 95% exact confidence interval will be calculated for AE rates and SAE rates overall and for organ class.
2. Ability to Complete all 3 MCS Treatments [ Time Frame: Change from Baseline to 3-Months Following Completion of Treatments ]
   Number of subjects completing all 3 treatments.
3. Patient Reported Outcome Instrument: St. George's Respiratory Questionnaire (SGRQ) [ Time Frame: Change from Baseline to 3-Months Following Completion of Treatments ]
   Scale is 0-100; a higher score is worse

Secondary Outcome Measures :

1. Spirometry Testing [ Time Frame: Change from Baseline to 3-Months, 1 year, 2 year and 3 year Following Completion of Treatments ]
   FEV1, FEV1/FVC, VC, FIV1
2. 6 Minute Walk Test [ Time Frame: Change from Baseline to 3-Months, 1 year, 2 year and 3 year Following Completion of Treatments ]
   Number of meters walked in six minutes
3. Leicester Cough Questionnaire (LCQ) [ Time Frame: Change from Baseline to 3-Months, 1 year, 2 year and 3 year Following Completion of Treatments ]
   The total score range is 19-133; a higher score is better.
4. COPD Assessment Test (CAT) [ Time Frame: Change from Baseline to 3-Months, 1 year, 2 year and 3 year Following Completion of Treatments ]
   The total score range is 0-40; a higher score is worse
5. Visual Analog Scale (VAS) [ Time Frame: Change from Baseline to 3-Months, 1 year, 2 year and 3 year Following Completion of Treatments ]
   The total score range is 0-100; a higher score is worse
6. Modified Medical Research Council (mMRC) [ Time Frame: Change from Baseline to 3-Months, 1 year, 2 year and 3 year Following Completion of Treatments ]
   The total score range is 0-4; a higher score is worse

Other Outcome Measures:

1. Exacerbation Rate [ Time Frame: Change from Baseline to 3-Months, 1 year, 2 year and 3 year Following Completion of Treatments ]
   Annualized exacerbation rates
2. Airway Wall Thickness Using HRCT [ Time Frame: Change from Baseline to 3-Months, 1 year, 2 year and 3 year Following Completion of Treatments ]
   Lumen radius in mm.
3. Plasma Fibrinogen [ Time Frame: Change from Baseline to 3-Months, 1 year, 2 year and 3 year Following Completion of Treatments ]
   150-400mg/dL

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Males and females ≥40 to ≤75 years of age.
• Subject is able to read, understand, and sign a written Informed Consent in order to participate in the study.
• Subject agrees to continue maintenance pulmonary/COPD medications for the duration of the study.
• Diagnosis of chronic bronchitis (CB) and 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.)
• Pre-procedure post bronchodilator FEV1 of greater than or equal to 30% and less than or equal to 80% of predicted within 3 months of enrollment.
• Smoking history of at least 10 pack years.
• Non-smoking for a minimum of 6 months prior to consent and agrees to continue not smoking for the duration of the study.
• Subject is able to adhere to and undergo 3 (4 if in Phase A) bronchoscope procedures that includes lung biopsies and multiple MCS treatments in the opinion of the investigator

Exclusion Criteria:

• Subject has had an acute pulmonary infection or pneumonia within prior 6 weeks of study bronchoscopy.
• Subject has had a CB and/or COPD exacerbation (requiring steroids and/or antibiotics) within 6 weeks prior to study bronchoscopy, as defined by their treating physician
• Subject has clinically significant bronchiectasis or other respiratory disease other than chronic bronchitis and COPD.
• Diagnosis of asthma with an onset before 30 years of age
• Subject has bullous emphysema characterized as large bullae >30 millimeters on CT.
• Subject has had a transplant.
• Subject has the inability to walk >140 meters
• Subject has PaC02 >8kPa, or a PaO2<7kPa at room air.
• Subject has a RVSP >45mmHg or a LVEF<45% on 2D-cardiac echo.
• Subject has undergone lung surgery: pneumonectomy, lobectomy, bullectomy, lung volume reduction surgery
• Subject has had a prior lung device procedure, including emphysema stent(s) implanted, lung coils, valves, lung denervation or other devices for emphysema.
• Subject is unable to temporarily discontinue use of anticoagulant therapy:

warfarin, Coumadin, LMWH, heparin, clopidogrel (or equal)

• Subject is on >10 mg of prednisolone/day.
• Subject has a serious medical condition, such as: uncontrolled congestive heart failure, uncontrolled angina, myocardial infarction in the past year, renal failure, liver disease, cerebrovascular accident within the past 6 months, uncontrolled diabetes, hypertension, autoimmune disease or uncontrolled gastric reflux
• Subject is pregnant, nursing, or planning to get pregnant during study duration.
• Subject has received chemotherapy within the past 6 months or is expected to receive chemotherapy during participation in this study.
• Subject is or has been in another clinical investigational study within 6 weeks of baseline.
• Subject has known sensitivity to medication required to perform bronchoscopy (such as lidocaine, atropine, and benzodiazepines).
• Subject has been in another clinical investigational study within 6 weeks of baseline.

Contacts and Locations

Locations

Canada, British Columbia

St. Paul's Hospital

Vancouver, British Columbia, Canada

Netherlands

University Medical Center Groningen

Groningen, Netherlands

United Kingdom

Chelsea and Westminster Hosptial/Royal Brompton Hosptial

London, United Kingdom, SW10 9NH

Sponsors and Collaborators

CSA Medical, Inc.

Investigators

• Study Director: Heather Nigro; CSA Medical

More Information

Additional Information:

accessed 5.12.2015 

Publications:

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Innes AL, Woodruff PG, Ferrando RE, Donnelly S, Dolganov GM, Lazarus SC, Fahy JV. Epithelial mucin stores are increased in the large airways of smokers with airflow obstruction. Chest. 2006 Oct;130(4):1102-8.

Ramos FL, Krahnke JS, Kim V. Clinical issues of mucus accumulation in COPD. Int J Chron Obstruct Pulmon Dis. 2014 Jan 24;9:139-50. doi: 10.2147/COPD.S38938. eCollection 2014. Review.

Godwin BL, Coad JE, "Healing responses following cryothermic and hyperthermic tissue ablation. " SPIE Proceedings 2009: Volume 7181, p1-9

Sciurba FC, Ernst A, Herth FJ, Strange C, Criner GJ, Marquette CH, Kovitz KL, Chiacchierini RP, Goldin J, McLennan G; VENT Study Research Group. A randomized study of endobronchial valves for advanced emphysema. N Engl J Med. 2010 Sep 23;363(13):1233-44. doi: 10.1056/NEJMoa0900928.

Shah PL, Zoumot Z, Singh S, Bicknell SR, Ross ET, Quiring J, Hopkinson NS, Kemp SV; RESET trial Study Group. Endobronchial coils for the treatment of severe emphysema with hyperinflation (RESET): a randomised controlled trial. Lancet Respir Med. 2013 May;1(3):233-40. doi: 10.1016/S2213-2600(13)70047-X. Epub 2013 Apr 23.

Gibson PG. Cough is an airway itch? Am J Respir Crit Care Med. 2004 Jan 1;169(1):1-2.

Jeffery P, Holgate S, Wenzel S; Endobronchial Biopsy Workshop. Methods for the assessment of endobronchial biopsies in clinical research: application to studies of pathogenesis and the effects of treatment. Am J Respir Crit Care Med. 2003 Sep 15;168(6 Pt 2):S1-17. Review.

Pulmonary Physiology, Levitzky M. 7th ed. 2007, The McGraw-Hill Companies

Smith BM, Hoffman EA, Rabinowitz D, Bleecker E, Christenson S, Couper D, Donohue KM, Han MK, Hansel NN, Kanner RE, Kleerup E, Rennard S, Barr RG. Comparison of spatially matched airways reveals thinner airway walls in COPD. The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study and the Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS). Thorax. 2014 Nov;69(11):987-96. doi: 10.1136/thoraxjnl-2014-205160. Epub 2014 Jun 13.

• Responsible Party: CSA Medical, Inc.
• ClinicalTrials.gov Identifier: NCT02483637
• Other Study ID Numbers: 012
• First Posted: June 29, 2015
• Last Update Posted: November 25, 2019
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by CSA Medical, Inc.:

spray cryotherapy; cryotherapy; chronic bronchitis; airflow restrictions

Additional relevant MeSH terms:

Bronchitis; Bronchitis, Chronic; Acute Disease; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Infections; Disease Attributes; Pathologic Processes; Pulmonary Disease, Chronic Obstructive