A Randomized Controlled Trial Comparing Non-ischemic Hypothermic Cardioplegic Perfusion to Ischemic Cold Static Preservation of Donor Hearts in Adult Cardiac Transplantation
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- Region Skane
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Short-term graft failure
研究概览
简要总结
The overall aim of this proposal is to compare a new state-of-the-art ex-vivo organ preservation method with standard ischemic cold static storage of donor hearts in adult cardiac transplantation.
Standard heart preservation before transplantation consists of cold ischemic storage of the heart. Clinical studies has shown that the morbidity and mortality risk increases with extension of the allograft ischemic time over four hours. For each additional hour the mortality risk increase with 25% the first year. This time constrained is costly and results in severe logistical problems, leading to loss of transplantable organs.
Initially the study is prospective, single-institution, open-label, non-randomised trial comparing the NIHP method with the conventionally SCS in adult heart transplanted patients at Skane University Hospital, Lund, Sweden. Six patients will be transplanted using the non-ischemic hypothermic cardioplegic perfusion. These will be compared with contemporary control patients transplanted with standard ischemic cold static storage. The results will be analysed and reported.
After the initially six patients have been completed, the study will become a single center, prospective, open, blinded endpoint, randomized, controlled clinical trial including 34 patients.
The primary end-point is a composite of mortality, primary graft dysfunction (PGD), need for extra corporal support, or acute cellular rejection (ACR) within 30- days post-transplant. PGD and ACR will be accessed blinded.An improved preservation of the transplanted organ will reduce the major limitations for survival in the early post-transplant period such as non-specific graft failure and acute rejection. Furthermore, it will make it possible to increase the donor pool.
详细描述
SURVEY OF THE FIELD
Ischemia and reperfusion (I/R)-elicited tissue injury contributes to morbidity and mortality4. In organ transplantation, it is a major challenge. The imbalance in metabolic supply and demand within the ischemic organ results in tissue hypoxia and microvascular dysfunction4. The following reperfusion enhances the activation of innate and adaptive immune responses resulting in a cell death programs4,5. Furthermore, it has been report that miRNA expression profile for heart transplantation is associated with I/R injury. Standard heart preservation before transplantation consists of cold ischemic storage of the heart. Clinical studies have shown that the mortality risk increases sharply with extension of the allograft ischemic time over 4 hours. For each additional hour, the mortality risk increase with 25% the first year. Different myocardial cardioplegic preservation solutions and an ex-vivo perfusion machine have been developed. That technique includes use of whole blood from deceased donor and a normothermic beating heart consuming nutrients during the preservation. Despite some promising experimental results, no consistent differences in outcome have been found. Improved preservation of the endothelium of the coronary arteries is instrumental to achieve improved patient short and long term outcome. A damaged endothelium could result in cardiac allograft vasculopathy (CAV) and increases the risk of ACR. Therefore, prolonged time and improved storage of the donor heart would save lives.
PURPOSE AND AIM
The overall aim of this study is to compare a new state-of-the-art organ preservation technique, non-ischemic continous/intermittent hypothermic cardioplegic perfusion (NICHCP), on immediate and long term heart allograft function and rejection episodes, with standard ischemic cold static storage (ICSS) of donor hearts in adult cardiac transplantation.
A new ex-vivo heart perfusion technique where the heart is perfused during explantation, using an independent portable heart-lung-machine, has been developed by Prof. Steen's research group3. Pre-clinical studies have shown that the new technology using NICHCP of donor hearts can be safely applied for 24 hours in pigs, however this new perfusion technique has never been used on man.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
PGD and ACR assessment will be performed by a blinded access
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •Listed for heart transplantation
- •Signed informed consent form
排除标准
- •Previous solid organ or bone marrow transplantation
- •4 or more previous sternotomies
- •known malignancy
- •kidney failure (estimated creatinine clearness, GFR <30)
- •liver failure (ASAT, ALAT or total Bilirubin) > 5 times upper limit of normal, or INR >2.0,
- •ongoing septicemia
- •systemic inflammatory disorders treated with corticosteroids
- •not able to understand Swedish
研究组 & 干预措施
Standard ischemic storage.
Ischemic cold static storage: a crystalloid solution (cardioplegia) is used to stop and preserve the heart. The heart is storage i a transport box containing ice to keep the temperature around 8°C.
干预措施: Ischemic cold static storage (Other)
Non-ischemic preservation.
Non-ischemic hypothermic perfusion (NIHP): The device, a portable heart-lung machine, is continous/intermittent perfused the heart with a new preservation solution at a temperature of 8°C.
干预措施: Non-ischemic preservation (Other)
结局指标
主要结局
Short-term graft failure
时间窗: Within 30-days post-transplantation
The Primary End-Point is defined as a composite endpoint of patient death due to graft failure, re-transplantation due to graft failure, severe primary graft dysfunction (PGD), need for extra corporal mechanical support such as ECMO within 7 days post transplantation, or acute cellular rejection (ACR) ≥ grade 2. PGD grading is done according to the International Society of Heart and Lung Transplantation guidelines. ACR assessment is based on post-transplant myocardial biopsy information and standard clinical evaluation.
次要结局
- Ischemia and reperfusion injury(Within 30-days post-transplantation)
- Long-term graft failure(Within 12-months post-transplantation)