BENTO - Bronchoscopic Lung Volume Reduction in Severe Emphysema Using Thermoablation

• ClinicalTrials.gov Identifier: NCT05717192
• Recruitment Status: Not yet recruiting
• First Posted: February 8, 2023
• Last Update Posted: December 14, 2023
• Sponsor: IHF GmbH - Institut für Herzinfarktforschung
• Information provided by (Responsible Party): IHF GmbH - Institut für Herzinfarktforschung

Tracking Information

• First Submitted Date: December 19, 2022
• First Posted Date: February 8, 2023
• Last Update Posted Date: December 14, 2023
• Estimated Study Start Date: January 1, 2024
• Estimated Primary Completion Date: October 1, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 6, 2023)

Change in patient-reported disease-specific quality of life [ Time Frame: 9 months ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 6, 2023)

• Vital status [ Time Frame: 3, 9 and 12 months ]
  alive/dead
• Change in FEV 1 [ Time Frame: 3, 9 and 12 months ]
  Change in forced expiratory pressure (FEV 1) in litres and percent
• Change in RV [ Time Frame: 3, 9 and 12 months ]
  Change in residual volume in litre and percent.
• Change in patient-reported, disease-specific quality of life [ Time Frame: 3, 9 and 12 months ]
  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.
• Serious Adverse Events [ Time Frame: 3, 9 and 12 months ]
  Rate of serious adverse events
• 6-minute walk test (6MWT) [ Time Frame: 3, 9 and 12 months ]
  Measures the distance (meter) in a 6-minute walk test.
• Severe excacerbations [ Time Frame: 3, 9 and 12 months ]
  Rate of severe exacerbations
• Mortality [ Time Frame: 3, 9 and 12 months ]
  All-cause mortality

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: BENTO - Bronchoscopic Lung Volume Reduction in Severe Emphysema Using Thermoablation
• Official Title: Bronchoscopic Lung Volume Reduction in Severe Emphysema Using Thermoablation
• Brief Summary: 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).
• 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
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Emphysema or Chronic Obstructive Pulmonary Disease

Intervention

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.

Study Arms

• 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
  Intervention: Device: InterVapor®-System
• 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).

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: February 6, 2023): 224
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 1, 2027
• Estimated Primary Completion Date: October 1, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.
• evidence of severe emphysema in high-resolution computed tomography
• functional evidence of severe pulmonary hyperinflation
• Collateral ventilation positive
• FEV1 post lysis between 20% and < 45% (calculated)
• Total lung capacity (TLC) ≥ 100% (calculated)
• Residual volume (RV) > 175% (calculated)
• arterial blood gas values of: PaCO2 ≤ 50 mmHg; PaO2 > 50 mmHg on room air.
• marked dyspnoea with a score ≥ 2 on the Medical Research Council modified scale (mMRC).
• 6-minute walk test > 140 metres
• Patient-specific, pre-interventional exhaustion of conservative treatment options
• optimised medical therapy (according to the GOLD guidelines)
• 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
• Participation in regular physical activities that go beyond the activities of daily living (e.g. a walking programme)
• 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 or thoracic surgery with removal of lung tissue
• 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 explanted valves in the target lobe with obvious airway obstruction 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Felix Herth, MD; +49 6221 396 1200; felix.herth@med.uni-heidelberg.de

Contact: Nancy Hofmann; +49 621 59577 214; hofmann@ihf.de

• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT05717192
• Other Study ID Numbers: MDR-0002
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

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.

• Current Responsible Party: IHF GmbH - Institut für Herzinfarktforschung
• Original Responsible Party: Same as current
• Current Study Sponsor: IHF GmbH - Institut für Herzinfarktforschung
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: IHF GmbH - Institut für Herzinfarktforschung
• Verification Date: January 2023