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

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

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.

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.

Inclusion Criteria:

1. Age > or equal to 40 and ≤ 75 years old

2. 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

3. Contralateral lung (to lung targeted for the initial BTVA treatment) with tissue to air ratio > 8%

4. FEV1 between 20% and 45% predicted

5. TLC > or equal to 100% predicted

6. RV > or equal to 200% predicted

7. Post-rehabilitation 6MWD > 140 meters

8. Marked dyspnea scoring > or equal to 2 on the mMRC

9. Arterial blood gas levels of: PaCO2 ≤ 50 mm Hg; PaO2 > 45 mm Hg on room air

10. 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

11. Optimized medical management (treatment consistent with GOLD guidelines)

12. 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

13. Current influenza vaccination

14. 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:

1. 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

2. DLCO < 20% predicted or immeasurable DLCO

3. BMI < 18kg/m2 or > 35 kg/m2

4. Clinically significant bronchiectasis with more than 30 ml productive cough

5. Heart and/or lung transplant, lung volume reduction surgery (LVRS), bullectomy, or thoracic surgery with removal of lung tissue

6. 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

7. Recent respiratory infections or COPD exacerbation in preceding 6 weeks

8. 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

9. Single large bulla (defined as > 1/3 volume of the lobe) or a paraseptal distribution of emphysema in lobe to be treated

10. Bacterial infection or symptoms indicative of active infection (i.e., fever, elevated white blood cell count)

11. 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

12. 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

13. Newly prescribed morphine derivatives within the last 4 weeks

14. Pregnant or breastfeeding

15. Pneumothorax or pleural effusion within previous 6 months

16. Indwelling pacemaker or implantable cardiac defibrillator (ICD)

17. Patients dependent on the sponsor or investigator

18. Current enrollment in any other investigational study which has not completed requisite follow-up