A Multi-center RCT to Evaluate Subsegmental BTVA Treatment for Severe Emphysema

Study Overview
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Brief Summary
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To compare the efficacy and safety of subsegmental treatment and segmental treatment with InterVapor in patients with severe emphysema

Official Title
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A Multi-center, Randomized Controlled Study to Evaluate the Efficacy and Safety of Precise Subsegmental Treatment With InterVapor for Severe Emphysema

Conditions
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Severe Emphysema

Intervention / Treatment
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* Procedure: BTVA treatment plus optimal medical therapy (GOLD guidelines)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age≥18 years old; Patients with severe emphysema and with at least two treatable subsegments and 1 treatable segment in the ipsilateral lung assessed by QCT; Non-smoking for 2 months prior to study enrollment, and remain abstinent from smoking for the duration of the study; 15%predicted≤FEV1≤50%predicted, TLC≥100% predicted, RV≥150% predicted (and RV/ TLC≥55%); 6MWD >140 meters (patients with lower limb disability or motor dysfunction will be exempted from the test) mMRC score≥2; Arterial blood gas levels of: PaCO2≤55 mmHg; PaO2>50 mmHg on room air; Mentally and physically able to cooperate with the study procedures and to provide informed consent prior to study enrollment. Exclusion Criteria: Contraindications to bronchoscopy, such as: Prior myocardial infarction within 1 month, unstable myocardial ischaemia, ejection fraction (EF) ≤ 40%; Active haemoptysis; Coagulation disorders; Malignant cardiac arrhythmia, severe pulmonary hypertension, extreme systemic failure, etc; Concomitant illnesses or medications that would pose a significant increased risk for complications following treatment with InterVapor. Examples of particular relevance include: immune system disorders, immunosuppressant medications of clinical relevance, bleeding disorders and unstable cardiovascular conditions, history of asthma or alpha-1 antitrypsin deficiency; Use of morphine derivatives within 4 weeks prior to screening; Taking more than 10 mg prednisolone or equivalent daily glucocorticoids at the screening visit; Recent COPD exacerbation in preceding 6 weeks; Severe emphysema in both the upper and lower lobes of the contralateral lungs, defined as %LAA-950 assessed by HRCT as a percentage of whole lung lobe volume > 40%; Presence of single large bulla (defined as > 1/3 volume of lobe) or a paraseptal distribution of emphysema in the target lobe; Presence of active pathogen related infection or symptoms indicative of active infection (e.g. fever, elevated WBC, etc.); History of heart and/or lung transplant, lung volume reduction surgery (LVRS), median sternotomy, bullectomy, thoracic surgery with removal of lung tissue and endobronchial lung volume reduction (via valves, coils, stents, etc.); Highly suspicious malignant pulmonary nodules in the lungs as assessed by specialist; Pregnant or breastfeeding; Current enrollment in any other investigational study which has not completed requisite follow-up; Any conditions assessed by investigator that make patients inappropriate for enrolment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 88 Years

Sexes Eligible for Study
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Male

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: subsegmental BTVA treatment plus optimal medical therapy (GOLD guidelines)<br>Patients in experimental group will be treated with the InterVapor System in at least 2 subsegments of different segments per single procedure. | Procedure: BTVA treatment plus optimal medical therapy (GOLD guidelines)<br>* Patients in experimental group will be treated with the InterVapor System in at least 2 subsegments of different segments. Patients in control group will be treated with the InterVapor System in at least 1 segment. A sequential procedure allows for at least 6 weeks and no longer than 6 months after the first procedure. Patients in both groups will be treated in the ipsilateral lobe in a single procedure with the air+tissue volume of at least≥500 ml and≤1,700 ml in per procedure. All patients will continue to receive optimal medical therapy (GOLD guidelines) for the duration of the study. Follow-up visits will be scheduled at 1, 3, 6 and 12 months following the second procedure with examination of pulmonary function tests, HRCT, 6-minute walk test, SGRQ-C, mMRC, CAT questionnaires. All adverse events during the study will be recorded.<br>|
| Active Comparator: segmental BTVA treatment plus optimal medical therapy (GOLD guidelines)<br>Patients in control group will be treated with the InterVapor System in at least 1 segment per single procedure. | Procedure: BTVA treatment plus optimal medical therapy (GOLD guidelines)<br>* Patients in experimental group will be treated with the InterVapor System in at least 2 subsegments of different segments. Patients in control group will be treated with the InterVapor System in at least 1 segment. A sequential procedure allows for at least 6 weeks and no longer than 6 months after the first procedure. Patients in both groups will be treated in the ipsilateral lobe in a single procedure with the air+tissue volume of at least≥500 ml and≤1,700 ml in per procedure. All patients will continue to receive optimal medical therapy (GOLD guidelines) for the duration of the study. Follow-up visits will be scheduled at 1, 3, 6 and 12 months following the second procedure with examination of pulmonary function tests, HRCT, 6-minute walk test, SGRQ-C, mMRC, CAT questionnaires. All adverse events during the study will be recorded.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in FEV1 | Improvement in FEV1 between experimental group vs control group at 6 months following the second procedure | 6 months following the second procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in lung volumes by HRCT | Changes in lung volumes from baseline as assessed by HRCT at 6,12 months | 6 and 12 months following the second procedure | 
| Changes in FEV1 | Changes in FEV1 from baseline at 12 months | 12 months following the second procedure | 
| Changes in Quality-of-Life score | Changes in Quality-of-Life score as assessed by the SGRQ-C questionnaire from baseline at 6,12 months | 6 and 12 months following the second procedure | 
| Changes in FVC | Changes in FVC from baseline at 6,12 months | 6 and 12 months following the second procedure | 
| Changes in RV | Changes in RV from baseline at 6,12 months: RV | 6 and 12 months following the second procedure | 
| Changes in TLC | Changes in TLC from baseline at 6,12 months | 6 and 12 months following the second procedure | 
| Changes in RV/TLC | Changes in RV/TLC from baseline at 6,12 months | 6 and 12 months following the second procedure | 
| Changes in DLCO | Changes in DLCO from baseline at 6,12 months | 6 and 12 months following the second procedure | 
| Changes in 6MWD | Changes in 6MWD from baseline at 6,12 months (patients with lower limb disability or motor dysfunction will be exempted from the test) | 6 and 12 months following the second procedure | 
| Changes in CAT | Changes in CAT from baseline at 6,12 months | 6 and 12 months following the second procedure | 
| Changes in mMRC | Changes in mMRC from baseline at 6,12 months | 6 and 12 months following the second procedure | 
| A binary responder rate analysis will be performed to determine Minimal Clinically Important Difference (MCID) | A binary responder rate analysis will be performed to determine Minimal Clinically Important Difference (MCID) at 6,12 months: %predicted FEV1≥12% difference from baseline SGRQ-C≥8 points difference from baseline 6MWD≥30m from baseline | 6 and 12 months following the second procedure | 
| Incidence of Adverse Events | Adverse events related to the procedure during or within 12 months after the operation | during or within 12 months after the operation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bronchoscopic Thermal Vapor Ablation (BTVA), Chronic obstructive pulmonary disease (COPD), Severe emphysema, Bronchoscopic lung volume reduction (BLVR)