Bronchoscopic RElease of Air Trapped in Hyperinflated Emphysematous Lung
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 48
- 试验地点
- 2
- 主要终点
- Rate of Serious Adverse Events (SAE) at 6 Months
研究概览
简要总结
The goal of this clinical trial is to test the feasibility of an implant for severe emphysema in up to 30 participants. The main questions it aims to answer are:
Is it safe? Does it work?
Participants who meet eligibility criteria will have up to two procedures 30 days apart, in which up to 3 implants will be placed in each lung during the procedure(s). Participants will be asked to return for follow-up visits at 30 days, and 3, 6, and 12 months after the procedure(s).
详细描述
This is a first-in-human, prospective, multi-center, single-arm study assessing the safety, feasibility and preliminary efficacy of the Apreo Implant for severe emphysema in up to 30 participants. Initially all participants will undergo an Apreo Procedure involving placement of up to three implants in a native bronchial tree of one lung followed by a second Apreo Procedure 30 days later to place up to three implants in the contralateral native lung bronchial tree if indicated.
Once the fifth participant has undergone his or her first implantation procedure, implantations in currently enrolled or new participants will be paused to allow for a Safety Review Committee (SRC) to convene and review safety data once the 5th participant has completed the 7-day phone follow-up after their second Apreo Procedure (or first if only one procedure). This would be at a minimum acute procedural safety for up to 10 implantation procedures conducted in these first 5 participants, 30-day safety assessments for all 5 participants after their first lung implantations, bronchoscopic inspection 30 days after implantation of all implants in the first lung, and 7-day safety data after their first and second lung implantations. The SRC will provide comments and recommendations, including the restart of implantation for new participants, if deemed appropriate.
After the first 10 participants have completed the 7-day phone follow-up after the second Apreo Procedure (or first if only one procedure), their safety data will be reviewed by the SRC. This would include at a minimum acute procedural safety for up to 20 implantation procedures conducted in these first 10 participants, 30-day safety assessments for all 10 participants after their first lung implantations, bronchoscopic inspection 30 days after implantation of all implants in the first lung, and 7-day safety data after their first and second lung implantations. Following the review of the first 10 participants' safety data, the SRC may allow any subsequently enrolled participants to undergo one Apreo Procedure (rather than two separate procedures if appropriate for a participant) to deploy Apreo Implants in both the left and right lung airways as indicated or to continue to have all participants undergo two separate Apreo Procedures if indicated. A total of up to 30 participants will be enrolled overall.
All participants will be followed at 30 days, three, six and twelve months post the first Apreo Procedure.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 35 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 35 and ≤ 80 years old
- •Computed tomography (CT) scan evidence of homogeneous or heterogeneous emphysema
- •At least one target lobe with > 35% destruction (percent of voxels with < -950 Hounsfield units on CT)
- •Post-bronchodilator ratio of FEV1/FVC < 0.7 at screening
- •Post-bronchodilator FEV1 percent predicted ≥20% and ≤50% of predicted at screening
- •Post-bronchodilator RV > 180% predicted
- •Post-bronchodilator RV/TLC ≥ 0.55 at screening
- •Marked dyspnea, scoring ≥ 2 on the modified Medical Research Council scale of 0-4
- •Cotinine testing at screening indicates nonsmoker and stopped smoking at least 8 weeks before entering the trial and agrees to refrain from smoking for duration of study participation
- •Participation in a pulmonary rehabilitation program and/or confirmed to have been engaged or attempted regular physical activity in the 12 months prior to the first Apreo Procedure and agrees to continue or restart regular physical activity for the duration of the study
- •Fully vaccinated for Covid-19 (up to date per Australian Government Guidelines) and has current pneumococcus and influenza vaccination (or documented clinical intolerance)
- •Cognitively and physically able to provide written informed consent and complete participant questionnaires
排除标准
- •Arterial blood PaCO2 > 60 mmHg (8 kPa) or PaO2 ≤ 45 mmHg (6 kPa)
- •DLCO <20% at screening
- •Steroid therapy of 10 mg prednisolone (prednisone) or more per day
- •Three or more acute exacerbations of COPD in the past year before enrollment
- •Two or more hospitalizations for acute exacerbations of COPD or respiratory infections in the past year before enrollment
- •Any acute exacerbation of COPD or respiratory infection less than 4 weeks before the first Apreo Procedure
- •Previous lung volume reduction surgery or lobectomy, segmentectomy or bullectomy, vapor, glue, or other pulmonary device implant
- •Known history of pulmonary arterial hypertension
- •Presence of a giant bulla (≥ 30% of hemithorax)
- •History of excessive dynamic airway collapse of the trachea or main bronchi
- •History of adult asthma or chronic bronchitis
- •Presence of suspicious pulmonary nodule/infiltrate that requires additional follow-up, diagnostics or treatment
- •Unequivocal and symptomatic bronchiectasis
- •Unequivocal lung cancer or other current cancer diagnosis except non-metastasized basal cell skin cancer
- •Uncontrolled hypertension (blood pressure that is inadequately treated or resistant to treatment) with a systolic > 200 mmHg or diastolic > 110 mmHg at screening or prior to first Apreo Procedure
- •Uncorrectable coagulopathy or other condition likely to increase risk of peri- or post- Apreo Procedure bleeding
- •On anticoagulant or antiplatelet therapy and unable or unwilling to hold for Apreo Procedure
- •Coronary artery disease with angina
- •History of myocardial infarction within 6 months
- •History of a stroke less than 1 year before the first Apreo Procedure
- •Clinical history of heart failure with documented LVEF ≤ 40%
- •Clinical history of diabetes with a HbA1c > 9.0%
- •Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 (CKD-EPI) OR participant with kidney failure (Stage 5 kidney disease)
- •Mechanical ventilator dependence except participants using nocturnal bi-level positive airway pressure (biPAP) or continuous positive airway pressure (CPAP) are allowed if it would not preclude safe implantation of the study device
- •Pregnant, lactating, or women of childbearing potential who plan to become pregnant within the study duration
- •Known hypersensitivity to nitinol
- •Significantly immunocompromised, such as organ transplant recipients, those with congenital immune deficiencies, AIDS, or severe rheumatoid arthritis
- •Any disease or condition likely to limit survival to less than one year
- •Concomitant illnesses or medications that may pose a significant increased risk for complications following an Apreo Procedure
- •Currently enrolled in another trial and actively receiving experimental treatment
- •Any condition in the opinion of the investigator that would interfere with safe and complete collection of study data including the safe conduction of bronchoscopy procedures
结局指标
主要结局
Rate of Serious Adverse Events (SAE) at 6 Months
时间窗: 6 Months
Rate of occurrence of serious adverse events related to the study device and/or study procedure through 6 months post-study procedure
次要结局
- Device Evaluation: Device Deployment Assessment(During Procedure)
- Efficacy Evaluation: Airway Patency at 30 Days(30 Days)
- Efficacy Evaluation: Airway Patency at 3 Months(3 Months)
- Efficacy Evaluation: Forced Expiratory Volume in 1 Second (FEV1) at 1-3 Days(1-3 Days)
- Device Evaluation: Device Usability Survey(During Procedure)
- Efficacy Evaluation: Airway Patency at 6 Months(6 Months)
- Device Evaluation: Instructions for Use (IFU) Survey(During Procedure)
- Efficacy Evaluation: Airway Patency at 12 Months(12 Months)
- Efficacy Evaluation: Mucus Assessment at 30 Days(30 Days)
- Efficacy Evaluation: Mucus Assessment at 3 Months(3 Months)
- Efficacy Evaluation: Computed Tomography (CT) Scan at 6 Months(6 Months)
- Efficacy Evaluation: CT Scan at 12 Months(12 Months)
- Efficacy Evaluation: FEV1 at 6 Months(6 Months)
- Efficacy Evaluation: Residual Volume (RV) at 6 Months(6 Months)
- Safety: Rate of SAEs(Through 12 Months)
- Safety: Rate of Adverse Device Effects(Through 12 Months)
- Efficacy Evaluation: Mucus Assessment at 6 Months(6 Months)
- Efficacy Evaluation: FEV1 at 30 Days(30 Days)
- Efficacy Evaluation: FEV1 at 3 Months(3 Months)
- Efficacy Evaluation: FEV1 at 12 Months(12 Months)
- Efficacy Evaluation: Mucus Assessment at 12 Months(12 Months)
- Efficacy Evaluation: Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) at 6 Months(6 Months)
- Efficacy Evaluation: Residual Volume (RV) at 12 Months(12 Months)
- Efficacy Evaluation: Arterial Blood Gas (ABG): PaO2 at 6 Months(6 Months)
- Efficacy Evaluation: Arterial Blood Gas (ABG): PaCO2 at 6 Months(6 Months)
- Safety: Procedural Complications(Through 24 hours post-procedure)
- Efficacy Evaluation: Forced Expiratory Volume at 1 Second/ Forced Vital Capacity (FEV1/FVC) at 1-3 Days(1-3 Days)
- Efficacy Evaluation: FEV1/FVC at 30 Days(30 Days)
- Efficacy Evaluation: FEV1/FVC at 3 Months(3 Months)
- Efficacy Evaluation: FEV1/FVC at 6 Months(6 Months)
- Efficacy Evaluation: FEV1/FVC at 12 Months(12 Months)
- Efficacy Evaluation: RV Assessed by Pulmonary Function Testing at 1-3 Days(1-3 Days)
- Efficacy Evaluation: RV Assessed by Pulmonary Function Testing at 30 Days(30 Days)
- Efficacy Evaluation: Residual Volume/Total Lung Capacity (RV/TLC) at 1-3 Days(1-3 Days)
- Efficacy Evaluation: RV Assessed by Pulmonary Function Testing at 3 Months(3 Months)
- Efficacy Evaluation: RV Assessed by Pulmonary Function Testing at 6 Months(6 Months)
- Efficacy Evaluation: RV Assessed by Pulmonary Function Testing at 12 Months(12 Months)
- Efficacy Evaluation: RV/TLC at 30 Days(30 Days)
- Efficacy Evaluation: RV/TLC at 3 Months(3 Months)
- Efficacy Evaluation: RV/TLC at 6 Months(6 Months)
- Efficacy Evaluation: RV/TLC at 12 Months(12 Months)
- Efficacy Evaluation: FVC at 12 Months(12 Months)
- Efficacy Evaluation: Six Minute Walk Test (6MWT) at 1-3 Days(1-3 Days)
- Efficacy Evaluation: Six Minute Walk Test (6MWT) at 30 Days(30 Days)
- Efficacy Evaluation: Forced Vital Capacity (FVC) at 1-3 Days(1-3 Days)
- Efficacy Evaluation: FVC at 30 Days(30 Days)
- Efficacy Evaluation: FVC at 3 Months(3 Months)
- Efficacy Evaluation: Six Minute Walk Test (6MWT) at 3 Months(3 Months)
- Efficacy Evaluation: Six Minute Walk Test (6MWT) at 6 Months(6 Months)
- Efficacy Evaluation: FVC at 6 Months(6 Months)
- Efficacy Evaluation: Six Minute Walk Test (6MWT) at 12 Months(12 Months)
- Efficacy Evaluation: Modified Borg Dyspnoea Scale at 1-3 Days(1-3 Days)
- Efficacy Evaluation: Modified Borg Dyspnoea Scale at 30 Days(30 Days)
- Efficacy Evaluation: Modified Borg Dyspnoea Scale at 3 Months(3 Months)
- Efficacy Evaluation: Modified Borg Dyspnoea Scale at 6 Months(6 Months)
- Efficacy Evaluation: Modified Borg Dyspnoea Scale at 12 Months(12 Months)
- Efficacy Evaluation: COPD Assessment Test (CAT) at 1-3 Days (CAT scores range from 0 to 40, with higher score denoting higher impact of COPD on a participant's life)(1-3 Days)
- Efficacy Evaluation: St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) at 1-3 Days (scores range from 0 to 100, with higher scores indicating more limitations to daily living)(1-3 Days)
- Efficacy Evaluation: St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) at 6 Months (scores range from 0 to 100, with higher scores indicating more limitations to daily living)(6 Months)
- Efficacy Evaluation: COPD Assessment Test (CAT) at 30 Days (CAT scores range from 0 to 40, with higher score denoting higher impact of COPD on a participant's life)(30 Days)
- Efficacy Evaluation: Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) at 3 Months (CAT scores range from 0 to 40, with higher score denoting higher impact of COPD on a participant's life)(3 Months)
- Efficacy Evaluation: COPD Assessment Test (CAT) at 6 Months (CAT scores range from 0 to 40, with higher score denoting higher impact of COPD on a participant's life)(6 Months)
- Efficacy Evaluation: COPD Assessment Test (CAT) at 12 Months (CAT scores range from 0 to 40, with higher score denoting higher impact of COPD on a participant's life)(12 Months)
- Efficacy Evaluation: St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) at 30 Days (scores range from 0 to 100, with higher scores indicating more limitations to daily living)(30 Days)
- Efficacy Evaluation: St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) at 12 Months (scores range from 0 to 100, with higher scores indicating more limitations to daily living)(12 Months)
- Efficacy Evaluation: St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) at 3 Months (scores range from 0 to 100, with higher scores indicating more limitations to daily living)(3 Months)
- Efficacy Evaluation: Modified Medical Research Council (mMRC) Dyspnea Scale (0=no breathlessness except with strenuous exercise to 4=too breathless to leave the house or breathless when dressing or undressing) at 1-3 Days(1-3 Days)
- Efficacy Evaluation: Modified Medical Research Council (mMRC) Dyspnea Scale (0=no breathlessness except with strenuous exercise to 4=too breathless to leave the house or breathless when dressing or undressing) at 30 Days(30 Days)
- Efficacy Evaluation: Modified Medical Research Council (mMRC) Dyspnea Scale (0=no breathlessness except with strenuous exercise to 4=too breathless to leave the house or breathless when dressing or undressing) at 3 Months(3 Months)
- Efficacy Evaluation: Modified Medical Research Council (mMRC) Dyspnea Scale (0=no breathlessness except with strenuous exercise to 4=too breathless to leave the house or breathless when dressing or undressing) at 6 Months(6 Months)
- Efficacy Evaluation: Modified Medical Research Council (mMRC) Dyspnea Scale (0=no breathlessness except with strenuous exercise to 4=too breathless to leave the house or breathless when dressing or undressing) at 12 Months(12 Months)