a randomized controlled trial of intervapor® in france - the target trial

Conditions: Emphysema

Summary: 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.

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.

Eligibility criteria:
inclusion criteria: 1. age \> 18 and ≤ 80 years old 2. 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) 3. post-bronchodilator fev1 ≥ 15% and ≤ 45% of predicted value 4. total lung capacity (tlc) ≥ 100% predicted 5. post-bronchodilator residual volume (rv) ≥ 200% predicted 6. 6-minute walk distance (6mwd) \> 100m and ≤ 450m 7. (partial pressure of oxygen) paco2 ≤ 45 mm hg; pao2 \> 45 mm hg on room air 8. non-smoking for 4 months prior to study enrollment as confirmed by: 1. negative urine analysis or serum cotinine level of ≤ 10 ng/ml, or negative co hb test or 2. if using smoking cessation product(s) containing nicotine at screening, serum cotinine level ≤ 13.7 ng/ml (or arterial carboxyhemoglobin ≤ 2.5%) 9. optimized medical management (consistent with gold guidelines) 1. pharmacological: 1.long acting bronchodilator (laba),long-acting muscarinic antagonists (lama), lama + laba, or laba + ics \> 1 year b. evidence of completed pulmonary rehabilitation 1. ≥ 6 weeks out-patient or ≥ 3 weeks in-patient within 12 months of enrollment; or, 2. 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: 1. dlco \< 20% predicted 2. uncontrolled pulmonary hypertension (systolic pulmonary arterial pressure \>45 mm hg) or evidence or history of cor pulmonale as determined by recent echocardiogram 3. clinically significant bronchiectasis 4. clinically significant (greater than 4 tablespoons per day) sputum production. 5. two (2) or more copd exacerbations or pneumonia episodes requiring hospitalization in the last year 6. evidence of active infection in the lungs at the time of procedure. 7. daily use of systemic steroids, \> 10 mg prednisolone (or equivalent) daily. 8. lung pathology of nodule not proven stable or benign 9. clinically significant pulmonary fibrosis 10. prior lung transplant, lung volume reduction surgery (lvrs), bullectomy, or lobectomy 11. 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 12. large bulla (defined as \> 1/3 volume of the lobe) 13. highly diseased upper and lower lobes in contralateral lung (%-950 hu density \>50%) 14. paraseptal emphysema in any segment targeted for treatment 15. myocardial infarction or congestive heart failure within 6 months of screening. 16. diagnosis of heart failure with left ventricular ejection fraction (lvef) \< 45% as determined by recent echocardiogram (completed within 3 months prior to screening). 17. unable to safely discontinue anti-coagulants or platelet inhibitors for 6 weeks post procedure. 18. body mass index (bmi) \> 32 kg/m2 19. patient taking immunosuppressive drugs for the treatment of cancer, rheumatic arthritis, autoimmune disease, or prevention of tissue or organ rejection. 20. subject is pregnant or lactating, or plan to become pregnant within the study timeframe 21. any disease or condition that is likely to limit survival to less than one year 22. concomitant illnesses or medications that may pose a significant increased risk for complications following treatment with intervapor® 23. currently enrolled in another clinical trial studying an experimental treatment. 24. any condition that would interfere with completion of the study including study assessments and study procedure including bronchoscopy.

Keywords: heterogeneous thermal vapor ablation bronchoscopy lvr lung volume reduction