A Randomized Controlled Trial of InterVapor® in France - The TARGET Trial

Study Overview
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Brief Summary
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This study is designed to prospectively document changes in FEV1 and health-related quality of life 12 months following sequential segmental treatment with InterVapor® in patients with heterogeneous emphysema with upper lobe predominance. For validity of the study, the results will be compared to patients that receive optimal medical therapy.

Detailed Description
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The primary objectives are to prospectively document changes in FEV1 and health-related quality of life 12 months following sequential segmental treatment with Bronchoscopic Thermal Vapor Ablation (BTVA) using the InterVapor system in patients with heterogeneous emphysema with upper lobe predominance. The French TARGET trial is a prospective, multi-center, single blind, randomized controlled study. 150 participants will be enrolled in the study (1:1 randomization with 75 InterVapor, 75 controls) with a 24-month follow-up period. Subjects randomized to the Control Group may be allowed to cross over to the treatment group and offered the InterVapor treatment once they have completed the protocol defined 12-month follow-up period.

Official Title
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Targeted Segmental Vapor Ablation Treatment of Emphysema With Upper Lobe Predominance: A Randomized Controlled Trial of InterVapor® in France - The TARGET Trial

Conditions
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Emphysema

Intervention / Treatment
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* Device: Treatment plus Optimal Medical Therapy
* Other: Optimal Medical Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 and ≤ 80 years old Heterogeneous emphysema with upper lobe predominance in at least one lung segment to be treated (defined as a Heterogeneity Index (HI) ≥ 1.2 per CT) Post-bronchodilator FEV1 ≥ 15% and ≤ 45% of predicted value Total lung capacity (TLC) ≥ 100% predicted Post-bronchodilator Residual volume (RV) ≥ 200% predicted 6-minute walk distance (6MWD) > 100m and ≤ 450m (Partial Pressure of Oxygen) PaCO2 ≤ 45 mm Hg; PaO2 > 45 mm Hg on room air Non-smoking for 4 months prior to study enrollment as confirmed by: negative urine analysis or serum cotinine level of ≤ 10 ng/mL, or negative CO Hb test OR If using smoking cessation product(s) containing nicotine at screening, serum cotinine level ≤ 13.7 ng/ml (or arterial carboxyhemoglobin ≤ 2.5%) Optimized medical management (consistent with GOLD guidelines) Pharmacological: 1.Long acting bronchodilator (LABA),Long-acting muscarinic antagonists (LAMA), LAMA + LABA, or LABA + ICS > 1 year b. Evidence of completed Pulmonary Rehabilitation ≥ 6 weeks out-patient or ≥ 3 weeks in-patient within 12 months of enrollment; or, Patient has or continues to participate in at home rehabilitation program (i.e. a walking program) within 6 weeks of enrollment under the supervision of a health care professional 10. Mentally and physically able to provide written informed consent to participate in the study. Protected people as defined by the Code de la Sante Publique cannot be included in the study Exclusion Criteria: DLCO < 20% predicted Uncontrolled pulmonary hypertension (systolic pulmonary arterial pressure >45 mm Hg) or evidence or history of cor pulmonale as determined by recent echocardiogram Clinically significant bronchiectasis Clinically significant (greater than 4 tablespoons per day) sputum production. Two (2) or more COPD exacerbations or pneumonia episodes requiring hospitalization in the last year Evidence of active infection in the lungs at the time of procedure. Daily use of systemic steroids, > 10 mg prednisolone (or equivalent) daily. Lung pathology of nodule not proven stable or benign Clinically significant pulmonary fibrosis Prior lung transplant, lung volume reduction surgery (LVRS), bullectomy, or lobectomy Prior lung volume reduction via endobronchial valves(s), coil(s), and/or polymer. Note: Patients whose endobronchial valves have been removed can be treated if: all valves removed ≥ 3 months prior to InterVapor and baseline bronchoscopy reveals no airway obstruction or obvious tissue granulation Large bulla (defined as > 1/3 volume of the lobe) Highly diseased upper and lower lobes in contralateral lung (%-950 HU density >50%) Paraseptal emphysema in any segment targeted for treatment Myocardial Infarction or congestive heart failure within 6 months of screening. Diagnosis of heart failure with Left Ventricular Ejection Fraction (LVEF) < 45% as determined by recent echocardiogram (completed within 3 months prior to screening). Unable to safely discontinue anti-coagulants or platelet inhibitors for 6 weeks post procedure. Body mass index (BMI) > 32 kg/m2 Patient taking immunosuppressive drugs for the treatment of cancer, rheumatic arthritis, autoimmune disease, or prevention of tissue or organ rejection. Subject is pregnant or lactating, or plan to become pregnant within the study timeframe Any disease or condition that is likely to limit survival to less than one year Concomitant illnesses or medications that may pose a significant increased risk for complications following treatment with InterVapor® Currently enrolled in another clinical trial studying an experimental treatment. Any condition that would interfere with completion of the study including study assessments and study procedure including bronchoscopy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Subjects will be randomized in a 1:1 ratio between treatment group and control group. Subjects randomized to the Control Group may be allowed to cross over to the treatment group and offered the InterVapor treatment at 12 months, once they have completed the protocol defined follow-up period.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment plus Optimal Medical Therapy<br>Patients will be treated with the InterVapor System and Optimal Medical Therapy | Device: Treatment plus Optimal Medical Therapy<br>* Patients will be treated with the InterVapor System in 1 to 2 segments in the upper lobes of each lung (2 to 3 segments total). Patients will also receive Optimal Medical Therapy. Guidelines for prescribing medical treatment for emphysema are published by the American Thoracic Society (ATS) and the National Heart Lung and Blood Institute/World Health Organization (NHLBI/World Health Organization , Global Initiative for Chronic Obstructive Lung Disease (GOLD) workshop summary).<br>* Other names: BTVA;|
| Active Comparator: Optimal Medical Therapy (Control)<br>Patients will be treated according to Optimal Medical Therapy | Other: Optimal Medical Therapy<br>* Patients will receive Optimal Medical Therapy. Guidelines for prescribing medical treatment for emphysema are published by the American Thoracic Society (ATS) and the National Heart Lung and Blood Institute/World Health Organization (NHLBI/WHO GOLD workshop summary).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in FEV1 between Treatment vs Control at 12 months | Percentage change in Forced expiratory volume in 1 second (FEV1) compared to active comparator: Change in FEV1, percent change from baseline to 12 months in FEV1, where FEV1 is expressed in raw units of volume (mL). | 12 months | 
| St. George's Respiratory Questionnaire for patients with Chronic Obstructive Pulmonary Disease (SGRQ-C) changes between Treatment vs Control at 12 months | Health-related Qualify of Life (SGRQ-C) compared to active comparator. This is calculated as change from baseline to 12 months in SGRQ-C Total Score. SGRQ-C scores range from 0 to 100. A higher score means a worse outcome. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in other measures of pulmonary function- Forced Expiratory Volume, absolute change- at 12, 18 and 24 months | Change in FEV1, abs: Absolute change from baseline to follow-up in FEV1, where FEV1 is expressed in raw units of volume (mL). | 12 months, 18 months, 24 months | 
| Improvement in other measures of pulmonary function- Forced Expiratory Volume, Percent change- at 12, 18 and 24 months | Change in FEV1, Percent Predicted value: Percent change from baseline to follow-up in FEV1, where FEV1 is expressed in percent predicted computed by European Respiratory Standard (ERS) standards. | 12 months, 18 months, 24 months | 
| Improvement in other measures of pulmonary function- Forced Expiratory Volume, Abs, PP change- at 12, 18 and 24 months | Change in FEV1, abs, PP: absolute change from baseline to follow-up in FEV1, where FEV1 is expressed in percent predicted computed by ERS standards. | 12 months, 18 months, 24 months | 
| Improvement in other measures of pulmonary function- Forced Vital Capacity(FVC) change- at 12, 18 and 24 months | Change in FVC: percent change from baseline to follow-up in Forced Vital Capacity, expressed in raw units of volume(mL) | 12 months, 18 months, 24 months | 
| Improvement in other measures of pulmonary function- Forced Vital Capacity Percent Predicted change- at 12, 18 and 24 months | Change in FVC PP: percent change from baseline to follow-up in Forced Vital Capacity, expressed in percent predicted computed by ERS standards | 12 months, 18 months, 24 months | 
| Improvement in other measures of pulmonary function- Residual Volume- at 12, 18 and 24 months | Percent change from baseline to follow-up in Residual Volume | 12 months, 18 months, 24 months | 
| Improvement in other measures of pulmonary function- Residual Volume-Abs at 12, 18 and 24 months | Percent change from baseline to follow-up in Residual Volume, where RV is expressed in raw units of volume (mL). | 12 months, 18 months, 24 months | 
| Improvement in other measures of pulmonary function- Residual Volume-Percent Predicted value at 12, 18 and 24 months | Percent change from baseline to follow-up in Residual Volume, where RV is expressed in percent predicted computed by ERS standards. | 12 months, 18 months, 24 months | 
| Improvement in other measures of pulmonary function- Residual Volume-Abs Percent Predicted value at 12, 18 and 24 months | Absolute change from baseline to follow-up in Residual Volume, where RV is expressed in percent predicted computed by ERS standards | 12 months, 18 months, 24 months | 
| Improvement in other measures of pulmonary function-Diffusing Capacity of Lung (DLCO)- Percent Predicted Value at 12, 18 and 24 months | Percent change from baseline to follow-up in Diffusing Capacity of the Lungs for Carbon Monoxide, where DLCO is expressed in percent predicted computed by ERS standards. | 12 months, 18 months, 24 months | 
| Improvement in other measures of pulmonary function-Diffusing Capacity of Lung (DLCO)- Absolute Percent Predicted Value at 12, 18 and 24 months | Absolute change from baseline to follow-up in Diffusing Capacity of the Lungs for Carbon Monoxide, where DLCO is expressed in percent predicted computed by ERS standards. | 12 months, 18 months, 24 months | 
| Changes in segmental lung volumes from as assessed by CT at 12, 18 and 24 months | Changes in segmental lung volumes from baseline to 12 months as assessed by CT | 12 months, 18 months, 24 months | 
| Changes in pulmonary function tests as assessed by body plethysmography measures at 12, 18 and 24 months | Changes in pulmonary function tests as assessed by body plethysmography measures at 12 months | 12 months, 18 months, 24 months | 
| Number of serious adverse events and fatal events | Number of serious adverse events (SAEs) and fatal events | 12 months, 18 months, 24 months | 
| Binary responder analysis to determine minimally clinical important difference for FEV1 at 12, 18 and 24 months | Binary responder analysis to determine Minimal Clinically Important Difference (MCID) for the following: • FEV1 (> 12% predicted) in Treatment vs Control at 12 months | 12 months, 18 months, 24 months | 
| Binary responder analysis to determine minimally clinical important difference for SGRQ-C at 12, 18 and 24 months | Binary responder analysis to determine Minimal Clinically Important Difference (MCID) for the following: • SGRQ (> 8 points) in Treatment vs Control at 12 months | 12 months, 18 months, 24 months | 
| Binary responder analysis to determine minimally clinical important difference for 6 Minute Walk Distance (6MWD) at 12, 18 and 24 months | Binary responder analysis to determine Minimal Clinically Important Difference (MCID) for the following: • 6MWD (> 26m) in Treatment vs Control at 12 months | 12 months, 18 months, 24 months | 
| Binary responder analysis to determine minimally clinical important difference for COPD Assessment Test (CAT) score at 12, 18 and 24 months | Binary responder analysis to determine Minimal Clinically Important Difference (MCID) for the following: • CAT Score (> 2 points) in Treatment vs Control at 12 months | 12 months, 18 months, 24 months | 
| Binary responder analysis to determine minimally clinical important difference for Shortness of Breath Questionnaire (SOBQ) score at 12, 18 and 24 months | Binary responder analysis to determine Minimal Clinically Important Difference (MCID) for the following: • SOBQ Score (> 5 points) in Treatment vs Control at 12 month | 12 months, 18 months, 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LVR, Heterogeneous, Thermal Vapor, Ablation, Bronchoscopy, Lung Volume Reduction