To assess the safety and effectiveness of Bronchial Rheoplasty for the treatment of the symptoms of chronic bronchitis in adult COPD patients with moderate to severe chronic bronchitis.
ID
Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy endpoint is the mean change from baseline to Month 6 in
the COPD Assessment Test (CAT) total score.
Secondary outcome
Secondary efficacy endpoints include both objective measures and subjective,
patient reported measures.
Objective Measures:
• Change from baseline to Month 6 in distal airway volume (DAV) at expiration
as determined by an independent core lab
• Rate of moderate and severe COPD exacerbations through Month 12, excluding
the two 30-day treatment recovery periods
Patient Reported Outcome Measures:
• CAT:
mean total scores at months 3 and 12
responder analyses at months 3, 6, and 12
• CAT Components 1 and 2, and their sum: mean total scores and responder
analyses at months 3, 6, and 12
• SGRQ: mean total scores and responder analyses at months 6 and 12
• CASA-Q: mean total scores in each domain at months 6 and 12
Background summary
Chronic bronchitis is a common clinical phenotype in COPD and is classically
defined as chronic cough and sputum production for 3 months per year in each of
2 successive years. The mucus hypersecretion phenotype associated with chronic
bronchitis leads to worse clinical outcomes, more frequent and severe
exacerbations, and poorer quality of life. Despite the impact of chronic
bronchitis on morbidity and mortality, little progress has been made in
identifying effective therapies. RheOx bronchial Rheoplasthy was designed to
address this unmet need in chronic bronchitis by directly targeting the
pathophysiology of mucus hypersecretion responsible for the symptoms of chronic
bronchitis through the ablation of the goblet and other hypersecretory cells of
the airway epithelium and mucosa, thereby reducing mucus secretion and
improving the symptoms of the disease.
Published results of 30 patients treated in two completed feasibility trials
demonstrated a favorable safety profile with no reported device related serious
adverse events, clinically meaningful improvements in quality of life as
measured by the CAT and SGRQ, and a reduction in mucus producing cells in the
airways. This study is designed to provide confirmatory evidence of the safety
and effectiveness RheOx for the treatment of the symptoms of chronic
bronchitis.
Study objective
To assess the safety and effectiveness of Bronchial Rheoplasty for the
treatment of the symptoms of chronic bronchitis in adult COPD patients with
moderate to severe chronic bronchitis.
Study design
Prospective, randomized, parallel group, double-blind, concurrently controlled,
multicenter clinical trial following patients to 2 years.
Intervention
Bronchoscopic bronchial Rheoplasthy treatment
Study burden and risks
Potential Risks
Multiple feasibility studies of RheOx have provided a preliminary understanding
of the potential risks to study participants from Bronchial Rheoplasty and how
those risks compare to its potential benefits.
Risks potentially associated with participation in the study include the
following:
Likely occurrence* refers to risks estimated to occur in more than more than
10% of patients
• Sore throat
• Coughing. Coughing up small amount of phlegm (mucous) is common for 24 hours
after the procedure. Coughing may continue for more than 24 hours.
• Hemoptysis
Moderately likely occurrence* are estimated to occur in 1 in 100 (1%), to 1 in
10 (10%) patients
• Infection including fever, pain or soreness
• Exacerbation including shortness of breath, increased color and/or quantity
of phlegm, cough, wheeze or chest tightness
low occurrence* are estimated to occur in less than 1 in 100 (1%) patients
• Bronchial perforation
• Tracheobronchomalacia
• Lung abscess
• Gastroparesis
• Pneumothorax including severe chest pain, trouble breathing, death
• Airway stenosis, scarring or injury including wheezing, hoarseness, shortness
of breath and/or respiratory distress
• Abnormal cardiac rhythm function including arrhythmia, atrial fibrillation,
ventricular fibrillation, death
• Allergic reaction including abnormal breathing, difficulty swallowing,
anxiety, chest pain, severe cough, lightheadedness or dizziness, sweating or
fainting, swelling of the face, eyes or tongue
• Significant pulmonary bleeding
• Death
Minimization of Anticipated Risks
All interventional clinical studies pose some risks to study participants, but
the study sponsor has undertaken every effort to ensure that risks are
minimized. The study is designed with a conservative, stepwise approach to
treating each patient. Patients will be treated in only one lung during a
given bronchoscopic session and are fully recovered for 1 month following the
index procedure. The airways of the right lung treated during the Index
procedure will be visualized and assessed prior to commencement of treatment of
the left lung. If the patient experiences any complications that preclude
continued participation in the study, then additional treatment is halted.
In addition, risks will be minimized by selecting investigators with knowledge
and experience in advanced pulmonary procedures and the treatment of advanced
COPD. Study investigators and their support staff will undergo a comprehensive
training program, based on the training program used in prior feasibility
studies and including both didactic and hands-on elements, prior to performing
any Bronchial Rheoplasty or sham procedures. The attending study sponsor*s
representative will be available during cases to guide the investigator,
monitor operation of the RheOx device, and answer any questions of the site
staff.
Finally, the study design incorporates a planned interim analysis, which will
include evaluation of safety as well as effectiveness outcomes, and
establishment of an independent DSMB to ensure that safety concerns are closely
monitored and addressed throughout the study.
Potential Benefits from Study Participation
There may be no direct benefits to the patient from participating in the
study.
Potential benefits to the patient of receiving Bronchial Rheoplasty treatment
with the RheOx include the following:
• A reduction in symptoms, especially cough and sputum production, associated
with chronic bronchitis, and an improved quality of life
• An enhanced level of clinical scrutiny compared to routine clinical care for
chronic bronchitis, which may provide some health benefits apart from any
direct benefits from Bronchial Rheoplasty. This applies to both arms in the
study, including control group patients who do not undergo crossover to
treatment after Month 12.
In addition, this study may help other chronic bronchitis patients seeking
alternative treatments gain access to a new, minimally invasive therapy for
their disease. Through potential improvements in treatment outcomes,
availability of this new therapy may reduce the burden of chronic bronchitis on
the healthcare system.
Risk / Benefit Conclusion
The study sponsor has determined that this clinical study is justified because
the overall potential benefits to the patient and to the chronic bronchitis
population from participation in the study outweigh the potential risks to the
patient.
Industrial Road 1531
San Carlos 94070 CA
US
Industrial Road 1531
San Carlos 94070 CA
US
Listed location countries
Age
Inclusion criteria
1. Patient is at least 35 years of age.
2. Patient has chronic bronchitis, defined as productive cough for three months
in each of two successive years, whereas other causes of productive cough have
been ruled out.
3. Patient has a CAT score >= 10.
4. Patient has an SGRQ score >= 25.
5. Patient*s responses to the first two questions of the CAT instrument sum to
>= 7 points or the sum is 6 points and the patient*s total CAT score is > 20
points.
6. Patient has FEV1/FVC < 0.7.
7. Patient has a pre-procedure post-bronchodilator FEV1 percent predicted of >=
30%.
8. Patient is receiving guideline directed pharmacotherapy which includes one
or more long acting bronchodilator (LAMA, LABA) with or without an inhaled
corticosteroid for at least 8 weeks prior to randomization
9. Patient has a cigarette smoking history of at least ten pack years.
10. In the opinion of the Primary investigator, patient is able to undergo 2
bronchoscopies under general anesthesia and is able to adhere to the study
follow-up schedule.
11. Patient has provided informed consent.
Exclusion criteria
1. Patient has known unresolved lower respiratory tract infection (e.g.,
pneumonia, mycobacterium avium-intracellulare infection (MAI), fungus,
tuberculosis).
2. Patient has a steroid-dependent condition requiring >10 mg of oral
corticosteroid per day.
3. Patient has any implantable electronic device (e.g., pacemaker, cardioverter
defibrillator, neuro-stimulation devices).
4. Patient has a history of arrhythmia within past two years which includes
tachy-atrial arrhythmias, any ventricular tachy-arrhythmias, or sinus
bradycardia with heart rate less than 45 beats per minute.
5. Patient has unresolved lung cancer.
6. Patient has a pulmonary nodule or cavity that in the judgement of the
Primary investigator may require intervention during the course of the study.
7. Patient had prior lung surgery, such as lung transplant, LVRS, lobectomy,
lung implant/prosthesis, metal airway stent, valves, coils or bullectomy. Prior
pneumothorax without lung resection, pleural procedures without surgery, or
segmentectomy are acceptable.
8. Patient has emphysema of greater than or equal to 20% as quantified on
baseline HRCT scan (low attenuation area less than -950HU) as determined by the
CT Core Lab.
9. Patient has asthma based on Global Initiative for Asthma (GINA) criteria.
10. Patient has clinically significant bronchiectasis influencing the patient*s
clinical symptoms of cough and phlegm.
11. Patient has actively smoked (including tobacco, marijuana, e-cigarettes,
vaping, etc.) within the last 6 months.
12. Patient is unable to walk over 225 meters in 6 minutes.
13. Patient has a serious medical condition that, in the Primary investigator*s
opinion, could compromise patient safety or confound the interpretation of the
patient*s response to therapy (e.g., congestive heart failure, cardiomyopathy,
or myocardial infarction in the past year, renal failure, liver disease
cerebrovascular accident within the past 6 months, uncontrolled diabetes (HbA1c
>8%), uncontrolled hypertension (diastolic BP >100mmHg) or autoimmune disease
requiring treatment with immunosuppressant medications or a disease requiring
chemotherapy).
14. Patient has uncontrolled GERD.
15. Patient has known severe pulmonary hypertension.
16. Patient has a known sensitivity to medication required to perform
bronchoscopy (i.e., lidocaine, atropine, benzodiazepines).
17. Patient is pregnant, nursing, or planning to get pregnant during study
duration.
18. Patient is currently participating in another clinical study involving an
investigational product.
19. Patient is on anticoagulation for cardiovascular indications and, at the
discretion of the Primary investigator, is unable to have anticoagulants (i.e.,
Aspirin, Plavix, Coumadin) withheld for the bronchoscopy procedure per
institution*s standard of care.
20. Patient has known airway colonization with resistant organisms, such as
pseudomonas, methicillin-resistant Staphylococcus aureus (MRSA), Burkholderia
cepacia complex, Mycobacterium Tuberculosis (MTB), Mycobacterium abscessus
mucor or significant fungus.
21. Patient has had prior severe respiratory infection with SARS-CoV-2
(COVID-19) that required ICU support with non-invasive and/or invasive
mechanical ventilation.
22. Patient has known allergy to nickel.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT04677465 |
| CCMO | NL80887.042.22 |