A Pilot Study to Assess Treatment of Patients With Homogeneous Emphysema Using Sequential Segmental Bronchoscopic Thermal Vapor Ablation (NEXT STEP)

Study Overview
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Brief Summary
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This study is a Prospective, single arm, single center pilot study following outcomes for 12 months after initial BTVA treatment. The primary objectives of the study are to prospectively document the safety and efficacy of sequential segmental treatment with BTVA in patients with a homogeneous distribution of emphysema that are not candidates for endobronchial valve therapy.

Detailed Description
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The study will include patients with severe emphysema as defined by pulmonary function tests, a homogeneous distribution of emphysema as determined by CT, who are not eligible for endobronchial valve therapy based on fissure integrity as determined by CT. Enrollment will continue until 10 patients have been treated per protocol or until a maximum of 15 patients total have been treated. Patients will be enrolled at Thoraxklinik University of Heidelberg, Germany and followed for twelve (12) months. The follow up data collected will include pulmonary function testing (spirometry, body plethysmography, DLCO), exercise capacity (six minute walk test) and imaging findings (chest x-ray and CT). Dyspnea score (mMRC) and quality of life questionnaire (SGRQ-C) information will be obtained. Information regarding adverse events, serious adverse events, and major medical complications will be collected at each visit. Serious adverse events will be adjudicated by an independent medical monitor in order to establish relatedness to the InterVapor device and procedure. Descriptive statistics will be used to summarize all safety and efficacy data. There is no predefined hypothesis regarding safety, or efficacy. Monitoring of the study will be undertaken as a continuous process to ensure that high-quality data are obtained and to ensure compliance with study procedures.

Official Title
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A Pilot Study to Assess Treatment of Patients With Homogeneous Emphysema Using Sequential Segmental Bronchoscopic Thermal Vapor Ablation

Conditions
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Emphysema or COPD

Intervention / Treatment
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* Device: Bronchoscopic Thermal Vapor Ablation (BTVA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > or equal to 40 and ≤ 75 years old At least one lung with a homogeneous distribution of emphysema (defined as a heterogeneity index < 1.2 when calculated as the ratio of upper lobe to lower lobe %-950 and when calculated as the ratio of lower lobe to upper lobe %-950) and a fissure integrity score < 95% as measured by CT Contralateral lung (to lung targeted for the initial BTVA treatment) with tissue to air ratio > 8% FEV1 between 20% and 45% predicted TLC > or equal to 100% predicted RV > or equal to 200% predicted Post-rehabilitation 6MWD > 140 meters Marked dyspnea scoring > or equal to 2 on the mMRC Arterial blood gas levels of: PaCO2 ≤ 50 mm Hg; PaO2 > 45 mm Hg on room air Non-smoking for 2 months prior to study enrollment, as confirmed by negative urine point of contact strips or serum cotinine level of ≤ 10 ng/mL, or negative CO Hb test Optimized medical management (treatment consistent with GOLD guidelines) Evidence of completed pulmonary rehabilitation: ≥ 6 weeks out-patient or ≥ 3 weeks in-patient within 6 months of enrollment; or, Patient has or continues to participate in regular physical activity beyond activities of daily living (i.e. a walking program) for ≥ 6 weeks with 6 months of enrollment under the supervision of a health care professional Current influenza vaccination Mentally and physically able to cooperate with the study procedures, follow-up requirements, and are able and willing to provide informed consent to participate in the study. Exclusion Criteria: Any condition that would interfere with the completion of the study, follow-up assessments, bronchoscopy, or that would adversely affect study outcomes. Concomitant illnesses or medications that would pose a significant increased risk for complications following treatment with BTVA. Relevant examples of relevance include immune system disorders, immunosuppressant medications of clinical relevance, bleeding disorders and unstable cardiovascular conditions, history of asthma or alpha-1 antitrypsin deficiency DLCO < 20% predicted or immeasurable DLCO BMI < 18kg/m2 or > 35 kg/m2 Clinically significant bronchiectasis with more than 30 ml productive cough Heart and/or lung transplant, lung volume reduction surgery (LVRS), bullectomy, or thoracic surgery with removal of lung tissue Prior lung volume reduction via endobronchial valves(s), stent(s), coil(s), and/or polymer. Patients whose endobronchial valves have been removed can be treated if: all valves removed ≥ 6 months prior to BTVA and baseline bronchoscopy reveals no airway obstruction or obvious tissue granulation Recent respiratory infections or COPD exacerbation in preceding 6 weeks Unstable COPD (any of the following): >3 COPD related hospitalizations requiring antibiotics in past 12 months COPD related hospitalization in past 3 months daily use of systemic steroids, i.e. > 5 mg prednisolone Single large bulla (defined as > 1/3 volume of the lobe) or a paraseptal distribution of emphysema in lobe to be treated Bacterial infection or symptoms indicative of active infection (i.e., fever, elevated white blood cell count) History of any of the following: Left ventricular ejection fraction (EF) ≤ 40% Stroke Myocardial infarction or acute coronary syndrome in previous year Current use of anticoagulants (including warfarin, and NOACs such as dabigatran, rivaroxaban, apixaban, and similar). Patient is unable to stop antiplatelet therapy (including dipyridamole, clopidogrel, prasugrel, and ticlopidine) 7 days before and not restart until 7 days after study procedure. Known sensitivity to medications required to perform bronchoscopy Pulmonary hypertension: Peak systolic PAP > 45 mm Hg or Mean PAP > 35 mm Hg Right heart catheter measurements (if available) will be considered definitive over echocardiography or cardiac scintigraphy measurements Newly prescribed morphine derivatives within the last 4 weeks Pregnant or breastfeeding Pneumothorax or pleural effusion within previous 6 months Indwelling pacemaker or implantable cardiac defibrillator (ICD) Patients dependent on the sponsor or investigator Current enrollment in any other investigational study which has not completed requisite follow-up

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single arm Pilot Study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BTVA Treatment<br>All patients that will receive Bronchoscopic Thermal Vapor Ablation (BTVA) Treatment | Device: Bronchoscopic Thermal Vapor Ablation (BTVA)<br>* Bronchoscopic vapor delivery to airway segment(s) targeted for treatment<br>* Other names: InterVapor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of SAEs, Major Medical complications, and unanticipated serious adverse device effects (USADEs) (safety endpoint) | Occurrence of SAEs, Major Medical complications, and unanticipated serious adverse device effects (USADEs) (safety endpoint) | Baseline to 6 months | 
| Change in FEV1 (efficacy endpoint) | Change in FEV1 (efficacy endpoint) | Baseline to 6 months | 
| Change in St Georges Respiratory Questionnaire for COPD Patients (SGRQ-C) score (efficacy endpoint) | This trial will utilize the SGRQ-C which is a shortened version of the SGRQ questionnaire. The SGRQ is a validated, disease-specific questionnaire that measures health-related quality of life in patients with COPD. The instrument has 3 domains (activity, symptoms, and impacts) and a total score. A Total and three-component scores are calculated: Symptoms; Activity; Impacts. Each questionnaire response has a unique empirically derived 'weight'. The lowest possible weight is zero and the highest is 100. Each component of the questionnaire is scored separately. Sum of maximum possible weights for each component and Total: Symptoms 566.2, Activity 982.9, Impacts 1652.8. Total (sum of maximum for all three components) 3201.9 Higher weights indicate worse outcomes. The difference in the domain scores and total score at follow-up visits relative to baseline will be calculated and reported. | Baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in FVC | Change in Forced Vital Capacity | Baseline to 6 months | 
| Change in FRC | Change in Forced Residual Capacity | Baseline to 6 months | 
| Change in RV | Change in Residual Volume | Baseline to 6 months | 
| Change in TLC | Change in Total Lung Capacity | Baseline to 6 months | 
| Change in RV/TLC | Change in Residual Volume/Total Lung Capacity | Baseline to 6 months | 
| Change in DLCO | Change in Diffusing capacity of the lung for carbon monoxide | Baseline to 6 months | 
| Change in Modified Medical Research Council (mMRC) Dyspnea scale | Change in dyspnea score. Grade Degree of Breathlessness Related to Activities Grade 0 No breathlessness except with strenuous exercise Grade 1 Breathlessness when hurrying on the level or walking up a slight hill Grade 2 Walks slower than people of the same age on the level because of breathlessness or has to stop for breath when walking at own pace on the level Grade 3 Stops for breath after walking about 100 yards or a few minutes on the level Grade 4 Too breathless to leave the house or breathless when dressing or undressing Max score=4, Min score=0 One score is reported based on grade. Higher values represent worse outcomes. For patients with a higher mMRC grade (e.g. ≥2) and clinical circumstances consistent with respiratory disease, measuring spirometry (e.g., FEV₁ and FVC), determining the patient's GOLD stage, helps guide therapeutic interventions. | Baseline to 6 months | 
| Change in 6MWD | Change in six minute walk distance | Baseline to 6 months | 
| Change in volume of the treated lobe(s) | Change in lung volume assessed by CT | Baseline to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Emphysema, Homogenous, Collateral Ventilation, Vapor, Ablation