ECP Study: Extracorporeal Photopheresis as Treatment of Cardiac Allograft Vasculopathy After Heart Transplantation and Evaluation of Platelet Function and Aggregation After Heart Transplantation
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Changes in CAV
研究概览
简要总结
This study evaluates coronary artery disease after heart transplantation and its relation to platelet function. Furthermore, we will evaluate extracorporeal photopheresis as treatment of coronary artery disease after heart transplantation.
详细描述
BACKGROUND
Part one:
Heart transplantation (HTX) is an excellent treatment of end stage heart failure with a mean survival of approximately 15.6 years (1). Long-term survival remains a challenge. With improvement of immunosuppressive therapy, incidences of acute cellular rejection (ACR) have declined, but after the first postoperative year, one of the main causes of death is cardiac allograft vasculopathy (CAV), which is an accelerated form of coronary artery disease (2).
ACR is a well-recognized phenomenon but the diagnosis of antibody-mediated rejection (AMR) has gained acceptance. AMR is associated with greater graft dysfunction, development of CAV and mortality. The diagnosis is based on clinical, histopathologic, immunopathologic and identification of donor-specific antibodies by solid phase assays (3,4). However, AMR is often clinically silent, and the histopathologic and immunopathologic evaluation may be associated with significant inter-observer variation. Identification of donor specific antibodies (DSA) could seem more suitable. In the GRAFT study, we found significantly increased levels of DSA in approximately 25% of HTX patients. They had subclinical reduced graft function, higher previous ACR burden and prevalence of CAV.
Guidelines recommend routinely evaluation of DSA, but the evidence of treating patients with DSA and no pathological findings is poor.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- •Age 18-100
- •Informed and signed consent
- •Positive Luminex analysis: Blood samples with DSA levels >3000 MFI
- •Coronary angiography with evidence of CAV (ISHLT class ≥1) according to ISHLT criteria's.
排除标准
- •Severe asthma or COLD with FEV1 < 50%*
- •2° or 3° AV block*
- •Pregnancy
- •Creatinine >250 mmol/l**
- •Platelet count below 20 x 109/L
- •History of allergy to 8-Methoxypsoralen (8-MOP)
- •History of light-sensitive disease
- •These patients will not be subjected to adenosine submission **These patients will not be subjected to OCT evaluation
- •Control groups:
- •120 patients with angiographically proven coronary artery disease treated with 75 mg aspirin daily for at least seven days (no other antithrombotic drugs are allowed). These data is already available.
- •60 healthy subjects on no medication - samples are taken before and after 75 mg aspirin daily for at least seven days. These data is already available.
- •As the data regarding the control groups are already available from previous studies at our department, these control patients are no considered actively included in this study. Hence, the patient population consists of the 60 HTx patients.
研究组 & 干预措施
Extracorporeal photopheresis
All patients with HLA antibodies receive 4 ECP-treatments in 2 months.
干预措施: Extracorporeal photopheresis (Other)
Extracorporeal photopheresis
All patients with HLA antibodies receive 4 ECP-treatments in 2 months.
干预措施: Aspirin 75mg (Drug)
Aspirin - single arm
1 tablet of Aspirin 75 mg administered x 1 daily for 7 days.
干预措施: Aspirin 75mg (Drug)
结局指标
主要结局
Changes in CAV
时间窗: Baseline and 12 months follow up
Changes in CAV assessed by CAG, OCT and advanced echocardiography
次要结局
- Platelet aggregation assessment related to CAV.(Baseline and 7 days after aspirin treatment.)
- Changes in platelet aggregation(Baseline and 7 days after aspirin treatment.)
- Changes in DSA levels(Baseline and 12 months follow up)
- Changes in exercise and longitudinal myocardial deformation capacity(Baseline and 12 months follow up)
- Changes in CFVR(Baseline and 12 months follow up)
研究者
Hans Eiskjær
Professor, DMSc
Aarhus University Hospital