Novel Lung Trial: Normothermic Ex Vivo Lung Perfusion (Evlp) As An Assessment Of Extended/Marginal Donor Lungs
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 252
- 试验地点
- 35
- 主要终点
- PAS Study Primary Endpoint
研究概览
简要总结
Human donor lungs that do not meet the standard clinical criteria for donor lung utilization but fit into the study inclusion criteria will be retrieved from the donor using current donor lung retrieval techniques.
详细描述
These lungs will be brought to the study transplant center to be re-assessed by the transplant team. The lungs will be physiologically assessed during ex vivo perfusion with Steen Solution. Perfusion of these lungs will be performed using Steen solution with the addition of methylprednisolone, heparin and antibiotics. With respect to the decision of lung utilization those organs with a delta pO2 (Δ pO2 = Pulmonary vein pO2 - pulmonary artery pO2) during ex vivo perfusion assessment > 350mmHg, good lung compliance, and a favorable opinion of the transplant surgeon will be considered transplantable. Lungs will be excluded for transplantation: if the Δ pO2 is less than 350mmHg or if they demonstrate >10% deterioration in any of the following functional parameters: pulmonary vascular resistance (PVR), dynamic compliance or airway pressures. Lungs will also be excluded if they are deemed unsuitable based on the clinical judgment of the lung transplant surgeon.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Recipient Inclusion/
排除标准
- •The recipient inclusion/exclusion criteria apply to patients enrolled in the control or EVLP treatment arms.
- •Recipient Inclusion Criteria
- •Requires single or bilateral lung transplant.
- •Male or Female, 18 years of age or older.
- •Subject or Subject's Representative provides a legally effective informed consent.
- •Recipient exclusion Criteria
- •A recipient is HIV positive.
- •A recipient has active Hepatitis.
- •Investigator believes that the recipient has infection that excludes them from transplant in the study.
- •To receive multi-organ transplant.
- •Is on hemodialysis or has chronic severe renal dysfunction. Severe renal dysfunction is defined as a glomerular filtration rate of 29 or less (mL/min/1.73m2).
- •Is to have planned concurrent cardiac procedures.
- •A recipient is a re-transplant. (A re-transplant is defined as a recipient having the removal and transplant of a previously transplanted lung. A recipient with a previously single lung transplant is eligible to enroll in the trial if it is for the other lung and within 6 months of previous transplant.)
- •A recipient is on Nova Lung, ECMO, or on mechanical ventilation. (CPAP and BIPAP are not exclusionary)
- •Donor Inclusion/Exclusion Criteria for EVLP Assessment
- •Donor Inclusion Criteria
- •The Donor lung must meet the following criteria to proceed with EVLP:
- •At the time of the clinical evaluation , the PaO2/FiO2 ≤ 300mmHg Or If PaO2/FiO2 > 30mmHg and the donor has any one or more of the following donor risk factors:
- •Multiple blood transfusions.
- •Pulmonary edema detected via CXR, bronchoscopy or palpation of lungs.
- •Donation after circulatory death donors.
- •Investigator evaluation of donor lung as "unsuitable" for standard criteria for lung transplant. List reason for "unsuitable" determination.
- •Donor Exclusion Criteria
- •Lung has significant pneumonia and/or persistent purulent secretions on bronchoscopy as determined by investigator.
- •Donor has known significant aspiration of gastric contents within the lung.
- •Donor lung has significant mechanical lung injury or trauma determined by chest x-ray, bronchoscopy, CT Scan or visual inspection.
- •Donor lung has active infectious disease such as HIV, Hepatitis B or C, HTLV or Syphilis. Note: This information is not available at the start of EVLP. Therefore this criteria can be assessed during or post EVLP, but prior to transplant.
- •Donor Inclusion/Exclusion Criteria for Transplant Suitability after EVLP
- •Donor Inclusion Criteria for Transplant Suitability
- •Surgeon must be clinically satisfied with the lung evaluation (i.e.) overall improvement, if not, the reason for refusal must be listed.
- •Stability or improvement of other lung function parameters during EVLP perfusion - PVR, Compliance, Airway Pressures.
- •Two delta PO2 greater than 350 mmHg, if two delta PO2 mm Hg are not met than three out of four of the following parameters must be present:
- •One delta PO2 of > 350 or absolute PO2 of >
- •Chest x-ray findings with absence or improvement of pulmonary edema/infiltrates
- •Compliance static (greater than 35 single and greater than 60 for a double)
- •Absence of consolidation by palpation
- •Donor Exclusion Criteria for Transplant Suitability after EVLP
- •All delta PO2 (s) are less than 350 mmHg (measured with a FiO2 set at 1.0) or all absolute PO2s are less than
- •Overall greater than 10-15% Functional deterioration of other lung function across all parameters (PVR, Compliance, PawP) with chest x-ray findings showing deterioration.
- •Donor lung positive for infectious diseases such as HIV, Hepatitis B or C, or Syphilis.
- •Note: This information is not available until at the start of EVLP. Therefore this criteria can be assessed during or post EVLP, but prior to transplant.
研究组 & 干预措施
EVLP Group
EVLP Group are those recipient lung transplant patients that received donor lungs that had been placed on the XPS™ with Steen Solution™ and undergone ex-vivo lung perfusion before being transplanted.
干预措施: XPS™ with Steen Solution™ (Device)
Control Group
Control Group are those recipient lung transplant patients that receive donor lungs via conventional transplant.
结局指标
主要结局
PAS Study Primary Endpoint
时间窗: 3 Years
The primary end point is a co-primary endpoint comparing survival rates and rates of grade 3 PGD at 72 hours with success if and only if both endpoints are met. Treatment Group (T) = EVLP transplant subjects Control Group (C) = standard transplant subjects Co-Primary Endpoints: Endpoint #1: Survival of T is non-inferior to C Ho: C - T ≥ M1 (T is inferior to the control by M1 or more) Ha: C - T \< M1 (T is inferior to the control by less than M1) where M1 = 0.12 Endpoint #2: Rate of grade 3 PGD at 72 hours for T is non-inferior to the rate for C Ho: C - T ≥ M2 Ha: C - T \< M2 where M2 = 0.12
PMA Study Primary Endpoint
时间窗: 72hrs and Survival
The primary end point is non-inferiority of the 3-year survival rate of the EVLP group as compared to 3-year survival rate of the control group. Ho: C - T ≥ M3 (T is inferior to the control by M3 or more) Ha: C - T \< M3 (T is inferior to the control by less than M3) where M3 = 0.12
次要结局
- PMA Secondary Endpoints(3 Years)
- PAS Secondary Endpoint:(5 Years)