Fissure Closure With the AeriSeal System for CONVERTing Collateral Ventilation Status (CONVERT) (CONVERT)
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT04559464 |
Recruitment Status :
Active, not recruiting
First Posted : September 22, 2020
Last Update Posted : March 22, 2024
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This is a prospective, open-label, multi-center, single-arm study to be conducted at up to 20 investigational sites. The Study plans to enroll up to 140 subjects with severe emphysema and collateral ventilation in the target lobe. This protocol is designed to evaluate the utility of the AeriSeal System to occlude collateral air channels in a target lung lobe with collateral ventilation (CV) and convert the target lung lobe to having little to no collateral ventilation. Subjects can then receive Zephyr Valves to achieve atelectasis in the targeted lobe, once AeriSeal has converted the CV+ lobe to a CV- one. Therefore, the study will have two Stages:
• Stage 1 will address the closure of the lobar fissure gaps (or collateral air channels) to block collateral ventilation (CV) with the AeriSeal System; conversion of the CV+ target lobe to CV-. Conversion of collateral ventilation will be evaluated by Chartis after 45 days. In the case of unsuccessful conversion, a second treatment of AeriSeal may be attempted, provided that the total application volume from both the initial and the repeat treatments does not exceed 40 mL in up to three (3) segments.
Clinical Assessments post-AeriSeal will be conducted at 28 and 45 days after first treatment and repeated after the second treatment, if applicable. For the purpose of protocol follow-up, the Day 45 post-AeriSeal final treatment will equal Day 0 for Stage 2.
• Stage 2 will include successfully converted subjects; CV+ to CV- conversion in Stage 1. Converted CV- target lobes will follow standard of care and receive CE marked Zephyr Endobronchial valves per the Zephyr IFU to perform bronchoscopic lung volume reduction (BLVR).
Clinical assessments will be conducted at 45 Days, 3-months, 6-months, and 12-months post-Zephyr Valve procedure.
Condition or disease | Intervention/treatment | Phase |
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Emphysema COPD Severe Emphysema | Device: AeriSeal Device: Zephyr Valves | Not Applicable |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 102 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Intervention Model Description: | Stage 1 will address the closure of the lobar fissure gaps (or collateral air channels) to block collateral ventilation (CV) with the AeriSeal System (conversion of the CV+ target lobe to CV-). Stage 2 will include successfully converted subjects in Stage 1. Converted CV- target lobes will follow standard of care and receive the Zephyr Endobronchial valves per the Zephyr Instructions for Use (IFU) to perform bronchoscopic lung volume reduction (BLVR). |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Fissure Closure With the AeriSeal System for CONVERTing Collateral Ventilation Status in Patients With Severe Emphysema; A Multicenter, Prospective Trial |
Actual Study Start Date : | December 15, 2020 |
Actual Primary Completion Date : | October 24, 2023 |
Estimated Study Completion Date : | October 2024 |
Arm | Intervention/treatment |
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AeriSeal and Zephyr Valve Treatment
Stage 1 will address the closure of the lobar fissure gaps (or collateral air channels) to block collateral ventilation (CV) with the AeriSeal System (conversion of the CV+ target lobe to CV-). Stage 2 will include successfully converted subjects in Stage 1. Converted CV- target lobes will follow standard of care and receive the Zephyr Endobronchial valves per the Zephyr Instructions for Use (IFU) to perform bronchoscopic lung volume reduction (BLVR). |
Device: AeriSeal
The AeriSeal Foam functions by blocking both small airways and collateral channels causing absorption atelectasis in the treated region of the lung. Occlusion with the foam also yields a targeted fibrotic response which durably reduces lung hyperinflation. The reduction in hyperinflation allows the healthier parts of the lung to re-inflate and improve breathing mechanics and gas exchange. In this study, the AeriSeal delivery will be limited to three segments that contain the collateral channel(s) between lung lobes. A minimum 10 mL volume of AeriSeal will be delivered per segment, with a total delivered volume limit of 40 mL per subject (including re-treatment, if needed) in a total of three segments. Device: Zephyr Valves The Zephyr Valves are implantable bronchial valves intended to control airflow in order to improve lung function in patients with hyperinflation associated with severe emphysema and/or to reduce air leaks.
Other Names:
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- Percentage of subjects converted from a positive collateral ventilation status (CV+) to having little to no collateral ventilation (CV-) in the treated lobe. [ Time Frame: 6-weeks post-AeriSeal treatment ]The primary AeriSeal endpoint will be the percentage of study subjects that are successfully converted from a positive collateral ventilation status (CV+) in the treated lobe to having little to no collateral ventilation (CV-) in the treated lobe six (6) weeks after delivery of AeriSeal.
- Treated Lobe Volume Reduction (TLVR) responders [ Time Frame: 45-days post-Zephyr Valve treatment ]The primary Zephyr Valve endpoint is the percentage of subjects achieving TLVR ≥ 350 mL (TLVR Responders) at 45-days post-valve treatment. That is, the percentage of CV+ to CV- converted subjects from Stage 1 who subsequently receive valves and have Treated Lobe Volume Reduction (TLVR) of ≥ 350 mL, via High-resolution computed tomography (HRCT) at 45-days post-valve treatment.
- Forced Expiratory Volume in 1 second (FEV1) [ Time Frame: 3-months ]Post-Bronchodilator Forced Expiratory Volume in 1 second (FEV1) change from Baseline to 3-months (Absolute and Percent changes)
- Residual volume (RV) [ Time Frame: 3-months ]Residual volume (RV) change from Baseline to 3-months (Absolute and Percent changes).
- Forced Expiratory Volume in 1 second (FEV1) [ Time Frame: 6-months and 12-months ]Post-Bronchodilator Forced Expiratory Volume in 1 second (FEV1) change from Baseline to 6-months and 12-months (Absolute and Percent changes)
- Residual volume (RV) [ Time Frame: 6-months and 12-months ]Residual volume (RV) change from Baseline to 6-months and 12-months (Absolute and Percent changes).
- Six-Minute Walk Distance (6MWD) [ Time Frame: 3-months, 6-months, and 12-months ]Change in Six-Minute Walk Distance (6MWD) from Baseline to 3-months, 6-months, and 12-months.
- St. George's Respiratory Questionnaire (SGRQ) Total Score [ Time Frame: 3-months, 6-months, and 12-months ]
Change in St. George's Respiratory Questionnaire (SGRQ) Total Score from Baseline to 3-months, 6-months, and 12-months.
The St. George's Respiratory Questionnaire measures health status (quality of life) in patients with diseases of airways obstruction. Scores range from 0 to 100, with higher scores indicating more limitations.
- Modified Medical Research Council Dyspnea Score (mMRC) [ Time Frame: 3-months, 6-months, and 12-months ]
Change in the Modified Medical Research Council (mMRC) Dyspnea Scale from Baseline to 3-months, 6-months, and 12-months.
The mMRC (Modified Medical Research Council) stratifies severity of dyspnea in respiratory diseases. The severity of dyspnea is rated on a scale of 0 to 4, with higher scores indicating more limitations.
- Total Lung Capacity (TLC) [ Time Frame: 3-months, 6-months, and 12-months ]Changes in TLC from Baseline to 3-months, 6-months, and 12-months (Absolute and Percent changes).
- Inspiratory Capacity (IC) [ Time Frame: 3-months, 6-months, and 12-months ]Changes in IC from Baseline to 3-months, 6-months, and 12-months (Absolute and Percent changes).
- Residual Volume/Total Lung Capacity (RV/TLC) ratio [ Time Frame: 3-months, 6-months, and 12-months ]Changes in the RV/TLC ratio from Baseline to 3-months, 6-months, and 12-months (Absolute and Percent changes).
- Inspiratory Capacity/Total Lung Capacity (IC/TLC) ratio [ Time Frame: 3-months, 6-months, and 12-months ]Changes in the IC/TLC ratio from Baseline to 3-months, 6-months, and 12-months (Absolute and Percent changes).
- Treated Lobe Volume Reduction (TLVR) [ Time Frame: 6-months and 12-months ]Changes in TLVR from Baseline to 6-months and 12-months.
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Ages Eligible for Study: | 40 Years to 75 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Subject is willing and able to provide Informed Consent and to participate in the study.
- Subject is ≥ 40 and ≤ 75 years of age at the time Informed Consent signature.
- Subject has at least one lobe with ≥ 50% emphysema destruction (at -910 HU) as determined by QCT.
- Subject has a diagnosis of homogenous or heterogeneous emphysema, confirmed by HRCT scan. Heterogeneous emphysema defined as ≥ 15% difference (at -910 HU) in emphysema destruction score of adjacent lobes by HRCT.
- Subject has a gap in the interlobar fissure that corresponds to one or more segments as determined by QCT.
- Subject has clinically significant dyspnea with a mMRC Dyspnea score ≥ 2.
- Subject has a Six-Minute Walk Distance ≥ 250 meters.
- Subject has post-bronchodilator FEV1 ≥ 15% predicted and ≤ 50% predicted.
- Subject has post-bronchodilator Total Lung Capacity ≥ 100% predicted.
- Subject has post-bronchodilator Residual Volume ≥ 150% predicted if heterogeneous emphysema and ≥ 200% predicted if homogeneous emphysema.
- Subject has stopped smoking for at least eight (8) weeks prior to Screening visit as confirmed by carboxyhemoglobin or cotinine levels.
- Subject has received preventive vaccinations against potential respiratory infections consistent with local recommendations or policy.
Exclusion Criteria:
- Subject has severe bullous emphysema where bulla is ≥ 1/3 of the total lung volume.
- Subject has had prior lung volume reduction surgery, prior lobectomy or pneumonectomy, prior lung transplantation, prior airway stent placement, prior ipsilateral pleurodesis, or prior endobronchial lung volume reduction therapy of any type.
- Subject has evidence of active respiratory infection.
- Subject has an ongoing COPD exacerbation or bronchospasm.
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Subject has a known allergy to the device components:
- Polyether block amide - PEBAX®
- Polyvinyl Alcohol
- Glutaraldehyde
- Nitinol (nickel-titanium) or its constituent metals (nickel or titanium)
- Silicone
- Subject requires invasive ventilatory support (NOTE: The use of continuous Positive Airway Pressure (CPAP) and BiPAP devices for Sleep Apnea is permitted).
- Subject has post-bronchodilator Diffusion Capacity (DLCO) < 20% predicted.
- Subject cannot tolerate corticosteroids or relevant antibiotics.
- Subject has other relevant comorbidities as judged by the Investigator or is deconditioned and cannot tolerate the stress of post-treatment inflammatory response.
- Subject has had three (3) or more COPD exacerbations requiring hospitalization during the year prior to Informed Consent signature.
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Subject has severe gas exchange abnormalities as defined by any one of the following (test conducted at rest on room air as tolerated, or on up to 4 L/min supplemental O2):
- PaCO2 ≥ 55 mm Hg (7.3 kPa)
- PaO2 < 45 mm Hg (6.0 kPa)
- SpO2 < 90%
- Subject has uncontrolled pulmonary hypertension, defined as peak pulmonary systolic pressure > 45 mm Hg on echocardiogram or right heart catheterization.
- Subject use of systemic steroids > 20 mg/day prednisolone or equivalent within 4 weeks of Informed Consent signature.
- Subject use of immunosuppressive agents within four (4) weeks of Informed Consent signature.
- Subject whose use heparins and oral anticoagulants (e.g., warfarin, dicumarol) cannot be discontinued according to local pre-procedural protocols. Note: antiplatelet drugs including aspirin and clopidogrel are permitted.
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Subject's CT scan indicates the presence of any the following radiologic abnormalities:
- Pulmonary nodule on CT scan greater than 0.8 cm in diameter (Does not apply if present for one (1) year or more without increase in size or if proven benign by biopsy).
- Radiologic picture consistent with active pulmonary infection, e.g., unexplained parenchymal infiltrate.
- Significant interstitial lung disease.
- Significant pleural disease.
- Subject's baseline EKG indicates non-atrial arrhythmias or conduction abnormalities.
- Subject has high cardiac risk after undergoing cardiac risk assessment in accordance with published guidelines or ischemic heart disease, congestive heart failure, renal failure, or cerebrovascular disease.
- Subject has clinically significant asthma (reversible airway obstruction), chronic bronchitis, or bronchiectasis.
- Subject has allergy or sensitivity to medications required to safely perform bronchoscopy under conscious sedation or general anesthesia.
- Subject participated in an investigational study of a drug, biologic, or device not currently approved for marketing within 30 days prior to Screening visit. Subjects being followed as part of a long-term surveillance of a non-pulmonary study that has reached its primary endpoint are eligible for participation in this study.
- Subject has Body Mass Index (BMI) < 18 kg/m2 or > 35 kg/m2.
- Subject is a female who is pregnant, breast-feeding, or planning to be pregnant in next 12 months.
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Subject has clinically significant abnormal screening laboratory test results per the Institution specific reference laboratory normal values for the following:
- White blood cells (total)
- Hematocrit
- Platelets
- Prothrombin time or INR
- Partial thromboplastin time
- Positive β-HCG Pregnancy test (if female)
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Subject has evidence of severe disease which in the judgment of the Investigator may compromise survival for the duration of the study (at least 12 months) e.g.:
- HIV/AIDs
- Active malignancy
- Stroke or Transient Ischemic attack (TIA) within 12 months of Screening visit
- Myocardial infarction within six (6) months of the Screening visit
- Congestive heart failure within six (6) months of the Screening visit defined as clinical evidence of right or left heart failure or left ventricular ejection fraction < 45% on echocardiogram
- Subject has uncontrolled diabetes mellitus.
- Subject has any other condition that the Investigator believes would interfere with the intent of the study or would make participation not in the best interest of the subject including but not limited to alcoholism, high risk for drug abuse, or noncompliance in returning for follow-up visits.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04559464
Australia | |
The Wesley Hospital | |
Brisbane, Australia | |
Macquarie University Hospital | |
Sydney, Australia | |
France | |
CHU Limoges | |
Limoges, France, 87042 | |
CHU Toulouse | |
Toulouse, France, 31059 | |
Germany | |
Charité - Universitätsmedizin Berlin | |
Berlin, Germany, 10117 | |
Ruhrlandklinik Essen | |
Essen, Germany, 45239 | |
ThoraxKlinik | |
Heidelberg, Germany, 69126 | |
Italy | |
ASST Spedali Civili, University Hospital | |
Brescia, Italy, 25123 | |
Netherlands | |
University Medical Center Groningen | |
Groningen, Netherlands, 9700 RB | |
Switzerland | |
University Hospital of Zurich | |
Zurich, Rämistrasse 100, Switzerland, 8006 | |
United Kingdom | |
Golden Jublilee National Hospital | |
Clydebank, Scotland, United Kingdom, G81 4DY | |
University Hospital of Wales | |
Cardiff, United Kingdom, CF14 4XW | |
Royal Brompton Hospital | |
London, United Kingdom, SW3 6NP | |
Nottingham University Hospitals | |
Nottingham, United Kingdom, NG5 1PB |
Study Director: | Joshua Percy | Pulmonx Corporation |
Responsible Party: | Pulmonx Corporation |
ClinicalTrials.gov Identifier: | NCT04559464 |
Other Study ID Numbers: |
630-0030-01 |
First Posted: | September 22, 2020 Key Record Dates |
Last Update Posted: | March 22, 2024 |
Last Verified: | March 2024 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Bronchoscopic lung volume reduction Zephyr Valves AeriSeal |
Pulmonary Emphysema Emphysema Pathologic Processes Pulmonary Disease, Chronic Obstructive Lung Diseases, Obstructive |
Lung Diseases Respiratory Tract Diseases Chronic Disease Disease Attributes |