BENTO - Bronchoscopic Lung Volume Reduction in Severe Emphysema Using Thermoablation

Bronchoscopic Lung Volume Reduction in Severe Emphysema Using Thermoablation

Prospective, 2-arm, randomised (2:1), multicentre, open-label clinical trial in patients with severe emphysema. The intervention arm will be treated with Bronchoscopic lung volume reduction in severe emphysema using thermoablation.The interventional treatment (bronchoscopic lung volume reduction) is compared with the usual conservative standard therapy (GOLD guidelines).

Study Overview

• Status: Recruiting
• Conditions: Emphysema or Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Device: InterVapor®-System

Detailed Description

Currently, there is less data on the use of bronchoscopic thermoablation (BTVA) for the treatment of patients with emphysema. However, the current studies suggest with a high degree of certainty that bronchoscopic lung volume reduction for severe emphysema using thermoablation has the potential to be a necessary treatment alternative. The trial study should therefore contribute to proving the benefit of this procedure as an effective and safe treatment option in order to guarantee emphysema patients sufficient, appropriate and economical care, taking into account evidence-based medical knowledge.

• Study Type: Interventional
• Enrollment (Estimated): 224
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Felix Herth, MD; Phone Number: +49 6221 396 1200; Email: felix.herth@med.uni-heidelberg.de
• Study Contact Backup: Name: Leschek Brachmann, Masters of Science; Phone Number: +49 621 59577 225; Email: leschek.brachmann@ihf.de

Study Locations

• Germany
  • Berlin, Germany, 14089
    • Recruiting
    • Gemeinschaftskrankenhaus Havelhöhe gGmbH Klinik für Anthroposophische Medizin
    • Contact: Hannah Wüstefeld, Dr. med.; Phone Number: 0049 30 365 280; Email: lunge@havelhoehe.de
    • Contact: Christian Grah, Dr. med.; Email: christian.grah@havelhoehe.de
    • Principal Investigator: Hannah Wüstefeld, Dr. med.
  • Berlin, Germany, 13353
    • Recruiting
    • Charite Campus Benjamin Franklin
    • Contact: Ralf-Harto Hübner, Dr. med.; Phone Number: 0049 30-450 653787; Email: ralf-harto.huebner@charite.de
    • Principal Investigator: Ralf-Harto Hübner, Dr.
  • Bonn, Germany, 53127
    • Not yet recruiting
    • Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik II
    • Contact: Dirk Skowasch, Prof.; Phone Number: +49 228-287-16670; Email: dirk.skowasch@ukbonn.de
    • Principal Investigator: Dirk Skowasch, Prof.
  • Essen, Germany, 4542329
    • Recruiting
    • Pneumologische Universitätsklinik Ruhrlandklinik
    • Contact: Rüdiger Karpf-Wissel, Dr.; Phone Number: 0049 201/ 433 4222; Email: Ruediger.Karpf-Wissel@rlk.uk-essen.de
    • Principal Investigator: Rüdiger Karpf-Wissel, Dr.
  • Halle, Germany, 06120
    • Recruiting
    • Universitatsklinikum Halle (Saale)
    • Contact: Stephan Eisenmann, Dr.; Phone Number: +49 345 5573238; Email: stephan.eisenmann@uk-halle.de
    • Principal Investigator: Stephan Eisenmann, Dr.
  • Heidelberg, Germany, 69126
    • Recruiting
    • Thoraxklinik University of Heidelberg
    • Principal Investigator: Felix Herth, Prof. Dr.
    • Contact: Felix Herth, Prof. Dr.; Phone Number: +49 6221 396 1200; Email: felix.herth@med.uni-heidelberg.de
  • Hemer, Germany, 58675
    • Recruiting
    • Lungenklinik Hemer
    • Principal Investigator: Kaid Darwiche, Prof. Dr.
    • Contact: Kaid Darwiche, Prof. Dr.; Phone Number: +49 2372 908 2179; Email: kaid.darwiche@lkhemer.de
    • Contact: Birte Schwarz; Phone Number: +49 2372-908-2179; Email: Birte.Schwarz@lkhemer.de
  • Immenhausen, Germany, 34376
    • Recruiting
    • Lungenfachklinik Immenhausen
    • Contact: Peter Hammerl, Dr. med.; Phone Number: +49 5673 501 1501; Email: hammerl@lungenfachklinik-immenhausen.de
    • Principal Investigator: Peter Hammerl, Dr. med.
  • Langen, Germany, 63225
    • Not yet recruiting
    • Asklepios Klinik Langen, Klinik für Innere Medizin III
    • Contact: Michael Bender, Dr. med.; Phone Number: +49 6103 912 61480; Email: mi.bender@asklepios.com
    • Contact: Thorsten Stein, Dr. med.; Email: th.stein@asklepios.com
    • Principal Investigator: Michael Bender, Dr. med.
  • Lüdenscheid, Germany, 58515
    • Recruiting
    • KlinKlinikuim Lüdenscheid, Klinik für Pneumologie, internistische Intensivmedizin, Infektiologie und Schlafmedizin
    • Contact: Wolfgang Hohenforst-Schmidt, Dr. med.; Phone Number: +49 2351 46-66225; Email: pneumologie@klinikum-luedenscheid.de
    • Principal Investigator: Wolfgang Hohenforst-Schmidt, Dr. med.
  • Münnerstadt, Germany, 97702
    • Recruiting
    • Thoraxzentrum Bezirk Unterfranken
    • Contact: Bernd Seese, Dr.; Phone Number: 0049 9733/62-3700; Email: b.seese@tzbu.de
    • Principal Investigator: Bernd Seese, Dr.
  • Stralsund, Germany, 18435
    • Recruiting
    • Helios Hanseklinikum Stralsund
    • Contact: Tom Bollmann, Dr. med.; Phone Number: +49 3831352588; Email: tom.bollmann@helios-gesundheit.de
    • Principal Investigator: Tom Bollmann, Dr. med.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age: ≥ 40 years and ≤ 75 years
• Written informed consent obtained from the patient
• Severe emphysema with indication for BTVA:
• bilateral heterogeneous emphysema of the upper lobes in GOLD stage 3/4 and
• evidence of severe emphysema in high-resolution computed tomography (not older than 6 months prior to inclusion) and
• functional evidence of severe pulmonary hyperinflation and
• FEV1 post lysis between 20% and < 45% (calculated) and
• Total lung capacity (TLC) ≥ 100% (calculated) and
• Residual volume (RV) > 175% (calculated) and
• arterial blood gas values of: PaCO2 ≤ 50 mmHg; PaO2 > 50 mmHg on room air and
• marked dyspnoea with a score ≥ 2 on the Medical Research Council modified scale (mMRC) and
• 6-minute walk test > 140 metres
• Patient-specific, pre-interventional exhaustion of conservative treatment options
• optimised medical therapy (according to the GOLD guidelines) and
• Non-smoker for 6 months prior to inclusion
• Evidence of completed pulmonary and geriatric rehabilitation in the last 4 years
• ≥ 6 weeks outpatient or
• ≥ 3 weeks inpatient or
• Individual Participation in regular physical activities that go beyond the activities of daily living (e.g. a walking programme)
• According to the investigator's assessment mentally and physically able to participate in the study procedures and visits
• Indication within the framework of an interdisciplinary case conference with specialists in pneumology, radiology and thoracic surgery in accordance with §3 of the guideline on quality assurance measures in accordance with § 136 Paragraph 1 Sentence 1 Number 2 SGB V for inpatient care with bronchoscopic lung volume reduction procedures for severe emphysema (QS-RL BLVR).

Exclusion Criteria:

• Any condition that would interfere with the conduct of the clinical trial follow-up or bronchoscopy or affect the outcome of the clinical trial
• DLCO < 20% (calculated)
• Body mass index (BMI) < 18 kg/m2 or > 32 kg/m2
• Pulmonary hypertension
• Peak systolic PAP > 45 mmHg or mean PAP > 25 mmHg
• Right heart catheter measurements are considered authoritative over echocardiogram measurements
• Clinically significant bronchiectasis
• Pneumothorax or pleural effusions within the last 6 months
• Heart and/or lung transplantation, surgical lung volume reduction (LVRS), bullectomy, lobectomy or pneumonectomy, pleurodesis or any surgery in the target lobes (upper lobes).
• Recent respiratory infection or COPD exacerbation in the last 6 weeks
• Unstable COPD (any of the following conditions):
• >3 COPD-related hospitalisations requiring antibiotics in the last 12 months
• COPD-related hospital stay in the last 3 months
• daily use of systemic steroids, > 5 mg prednisolone
• Single large bulla (defined as > 1/3 of the volume of the lobe) in the upper lobe or paraseptal emphysema distribution in the lobe being treated
• Coagulopathy or current use of anticoagulants
• Patients with current endobronchial valves or with valves explanted less than 6 months ago in the target lobe in a segment to be treated with InterVapor®.
• Patients with implanted, endobronchial coils (coils)
• Patients with previous endobronchial polymer/adhesive treatment
• Patients with immune system disorders or concomitant diseases that necessitate the use of immunosuppressants of clinical relevance
• History of any of the following conditions:
• Myocardial infarction or acute coronary syndrome in the previous year
• Hospitalisation for left heart failure in the last year
• clinically leading asthma disease or alpha-1-antitrypsin deficiency
• Known sensitivity to medications required to perform bronchoscopy
• Life expectancy < 12 months
• Newly prescribed morphine derivatives within the last 4 weeks
• Pregnancy at the time of inclusion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: InterVapor®-System; The intervention to be tested is bronchoscopic lung volume reduction (BTVA) using thermal ablation (InterVapor®, Uptake Medical, California, USA). This is performed in addition to standard conservative therapy in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines. The intervention can consist of a maximum of two partial interventions	Device: InterVapor®-System; The InterVapor System uses heated water vapor to ablate the airways and parenchyma within targeted regions of the lung. Lung remodeling occurs after an initial localized inflammatory response and a subsequent healing and repair. The remodeling of the tissue results in reductions in tissue and air volume in the targeted regions of the lung. The remodeled lung tissue does not re-inflate as a result of collateral ventilation. The lung volume reduction of diseased hyper-inflated lung segments after InterVapor treatment is expected to increase elastic recoil by reducing the most compliant segments of the lung, decompressing segments of healthier lung allowing for alveolar recruitment, and improving the mechanical efficiency of the respiratory muscles. These mechanical changes are anticipated to improve pulmonary function, exercise capacity and quality of life.
No Intervention: Standard of care; Standard conservative therapy in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines without the use of a BTVA (patient-specific documentation of therapeutic measures).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in patient-reported disease-specific quality of life	Change in patient-reported, disease-specific quality of life based on St. George's Respiratory Questionnaire (SGRQ-C) between randomisation and 9-month visit. 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.	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vital status	alive/dead	3, 9 and 12 months
Change in FEV 1	Change in forced expiratory pressure (FEV 1) in litres and percent	3, 9 and 12 months
Change in RV	Change in residual volume in litre and percent.	3, 9 and 12 months
Change in patient-reported, disease-specific quality of life	Change in patient-reported, disease-specific quality of life based on St. George's Respiratory Questionnaire (SGRQ-C) between randomisation and 9-month visit. 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.	3, 9 and 12 months
Serious Adverse Events	Rate of serious adverse events	3, 9 and 12 months
6-minute walk test (6MWT)	Measures the distance (meter) in a 6-minute walk test.	3, 9 and 12 months
Severe excacerbations	Rate of severe exacerbations	3, 9 and 12 months
Mortality	All-cause mortality	3, 9 and 12 months

Collaborators and Investigators

• Sponsor: IHF GmbH - Institut für Herzinfarktforschung

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2024
• Primary Completion (Estimated): April 25, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: December 19, 2022
• First Submitted That Met QC Criteria: February 6, 2023
• First Posted (Actual): February 8, 2023

Study Record Updates

• Last Update Posted (Actual): August 24, 2025
• Last Update Submitted That Met QC Criteria: August 19, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Emphysema
• Other Study ID Numbers: MDR-0002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Data Sharing Processes

All subject-level clinical, laboratory, and quality of life data will be preserved and shared with the Sponsor via eCRF. Shared data will be deidentified and original data will be main-tained at the investigator's site. Study design, recruitment progress and final results will be documented at clinicaltrials.gov. The trial data will be passed on to the extent permitted by the patient´s informed consent. Upon completion of the study, individual participant data will not be made available on data sharing repositories.

The steering committee will decide on sharing study data upon reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No