Kassimatis Theodoros, Qasem Anass, Douiri Abdel, Ryan Elizabeth G, Rebollo-Mesa Irene, Nichols Laura L, Greenlaw Roseanna, Olsburgh Jonathon, Smith Richard A, Sacks Steven H, Drage Martin
MRC Centre for Transplantation, King's College London, Guy's Hospital, London, UK.
Department of Primary Care and Public Health Sciences, King's College London, London, UK.
Trials. 2017 Jun 6;18(1):255. doi: 10.1186/s13063-017-1972-x.
Delayed graft function (DGF) is traditionally defined as the requirement for dialysis during the first week after transplantation. DGF is a common complication of renal transplantation, and it negatively affects short- and long-term graft outcomes. Ischaemia reperfusion injury (IRI) is a prime contributor to the development of DGF. It is well established that complement system activation plays a pivotal role in the pathogenesis of IRI. Mirococept is a highly effective complement inhibitor that can be administered ex vivo to the donor kidney just before transplantation. Preclinical and clinical evidence suggests that Mirococept inhibits inflammatory responses that follow IRI. The EMPIRIKAL trial (REC 12/LO/1334) aims to evaluate the efficacy of Mirococept in reducing the incidence of DGF in cadaveric renal transplantation.
METHODS/DESIGN: EMPIRIKAL is a multicentre double-blind randomised case-control trial designed to test the superiority of Mirococept in the prevention of DGF in cadaveric renal allografts, as compared to standard cold perfusion fluid (Soltran®). Patients will be randomised to Mirococept or placebo (Pbo) and will be enrolled in cohorts of N = 80 with a maximum number of 7 cohorts. The first cohort will be randomised to 10 mg of Mirococept or Pbo. After the completion of each cohort, an interim analysis will be carried out in order to evaluate the dose allocation for the next cohort (possible doses: 5-25 mg). Immunosuppression therapy, antibiotic and antiviral prophylaxis will be administered as per local centre protocols. The enrolment will take approximately 24 months, and patients will be followed for 12 months. The primary endpoint is DGF, defined as the requirement for dialysis during the first week after transplantation. Secondary endpoints include duration of DGF, functional DGF, renal function at 12 months, acute rejection episodes at 6 and 12 months, primary non-function and time of hospital stay on first admission and in the first year following transplant. Safety evaluation will include the monitoring of laboratory data and the recording of all adverse events.
The EMPIRIKAL trial is the first study to evaluate the efficacy of an ex vivo administered complement inhibitor (Mirococept) in preventing DGF in cadaveric human renal transplantation. Mirococept has a unique 'cytotopic' property that permits its retention in the organ microvasculature.
ISRCTN registry, ISRCTN49958194 . Registered on 3 August 2012.
传统上，移植肾功能延迟（DGF）被定义为移植后第一周内需要进行透析。DGF是肾移植的常见并发症，对移植肾的短期和长期预后均有负面影响。缺血再灌注损伤（IRI）是导致DGF发生的主要因素。众所周知，补体系统激活在IRI的发病机制中起关键作用。米罗西普是一种高效的补体抑制剂，可在移植前离体给予供肾。临床前和临床证据表明，米罗西普可抑制IRI后的炎症反应。EMPIRIKAL试验（REC 12/LO/1334）旨在评估米罗西普在降低尸体肾移植中DGF发生率方面的疗效。
方法/设计：EMPIRIKAL是一项多中心双盲随机病例对照试验，旨在测试米罗西普与标准冷灌注液（Soltran®）相比，在预防尸体肾移植中DGF方面的优越性。患者将被随机分为米罗西普组或安慰剂（Pbo）组，每组N = 80人，最多7个组。第一组将被随机分为10 mg米罗西普或Pbo组。每组完成后，将进行中期分析，以评估下一组的剂量分配（可能的剂量：5 - 25 mg）。免疫抑制治疗、抗生素和抗病毒预防将按照当地中心的方案进行。入组将持续约24个月，患者将被随访12个月。主要终点是DGF，定义为移植后第一周内需要进行透析。次要终点包括DGF的持续时间、功能性DGF、12个月时的肾功能、6个月和12个月时的急性排斥反应、原发性无功能以及首次入院和移植后第一年的住院时间。安全性评估将包括实验室数据监测和所有不良事件的记录。
EMPIRIKAL试验是第一项评估离体给予补体抑制剂（米罗西普）在预防尸体肾移植中DGF疗效的研究。米罗西普具有独特的“细胞定位”特性，可使其保留在器官微血管中。
ISRCTN注册库，ISRCTN49958194。于2012年8月3日注册。
