A Prospective, Observational Study in Pancreatic Allograft Recipients: The Effect of Risk Factors, Immunosuppressive Level and the Benefits of Scheduled Biopsies - on Surgical Complications, Rejections and Graft Survival
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Incidence of acute rejection episodes after pancreas- or pancreas- + kidney- transplantation
研究概览
简要总结
Several studies have shown acceptable results after Pancreas Transplantation (PTx) by substituting ATG with basiliximab, which is considered to convey a considerably lower number of adverse events. However, our experiences with ATG in PTx (introduced in 2004) are good, and our presumably gentle way of administrating the drug - directed by T-cell counts - is in fact unique. The potential advantages of reducing the overall corticosteroid (CS) load is obvious, as CS is a well-known pro-diabetic agent and causes severe long term adverse effects.
On this background, the investigators have very recently reduced our CS dosing (in the routine protocol) to a level corresponding to our Kidney Tx protocol (valid since 2009).
Thus, the investigators intend to prospectively investigate a single PTx cohort with the reduced CS immunosuppressive protocol by an observational study design, and compare with previous (historical) cohorts, who have received high dose CS.
Study hypotheses: i) Low-dose CS is as effective as high-dose corticosteroids with regards to efficacy/rejections; ii) The rate of surgical and infectious complications will be similar or lower in the low-dose group; iii) PTx rejection surveillance by DD (duodenoduodeno-stomy) and EUSPB (Endoscopic Ultra-Sound guided Pancreas Biopsies) is superior to traditional rejection surveillance; iv) Patient and graft survival is similar in the two groups
详细描述
- INTRODUCTION AND BACKGROUND
The first pancreas transplantation (PTx) was performed in Minnesota in 1966 by Kelly and colleagues (1). In recent years the number of procedures has grown considerably worldwide, and is now a well established treatment option for patients with diabetes mellitus with and without concomitant diabetic End-Stage Renal Disease (ESRD) (2-4). The indication for PTx is advanced and/or badly controlled diabetes mellitus ("brittle" diabetes, severe hypoglycemic episodes, "unawareness", etc). Solitary pancreas transplantation (SPT; without concomitant kidney transplantation) is usually classified as PTx alone (PTA), PTx after kidney transplantation (PAK) or PTx after islet transplantation (PAI). Kidney transplantation of the diabetic uremic population increases survival compared to long-term dialysis (5, 6). Transplant options for patients with diabetic end-stage nephropathy include simultaneous pancreas-kidney (SPK), live donor kidney (LDK) and deceased donor kidney (DDK) transplantation. SPK transplantation relieves not only the patient's uremia, but also alleviates the hyperglycaemic state of diabetes. Large international patient registries show that patient survival rates after SPK have reached more than 95% at 1 year and 87% at 5 years post-transplant, respectively (2). Nevertheless, PTx as treatment for type 1 diabetes has not gained the same popularity as transplantation of other organs, partly because PTx have been associated with a high rate of surgical complications; particularly bleeding, thrombosis and exocrine leakage. Furthermore, there has been a lack of reliable, non-invasive rejection monitoring instruments, and the invasive, percutaneous pancreas biopsies have been associated with a high rate of complications.
The difficulties encountered with PTx have to some extent been compensated by a very selective attitude towards the donors, but thereby making pancreas grafts a scarce resource. In contrast to other abdominal transplantations such as liver transplantation (LTx) and kidney transplantation (KTx), where repeated biopsies have been used for immunosurveillance, percutaneous biopsies of the pancreas-graft have traditionally been avoided due to a high rate of biopsy-related complications (exocrine leaks/fistulas and bleeding episodes). Thus, fear of acute rejections and lack of adequate rejection markers, have led to a rather intensive immunosuppressive load in PTx recipients. Solitary pancreas transplantation (SPT) has traditionally been subjected to even higher complication and rejection rates, with inferior graft and patient survival - thus favoring the combined SPK procedure. This has been attributed to an even worse rejection monitoring capability, without a "reporter" allograft kidney. No biochemical markers have proven to be effective in rejection surveillance.
Pancreas graft thrombosis is a feared complication in the postoperative course, partly due to the oversized vessels used (coeliac trunk/superior mesenteric artery/portal vein) in conjunction with the low blood flow through an isolated pancreas graft. In the native setting, these vessels also serve the intestines and spleen. Therefore, PTx poses a delicate balance between thrombosis and bleeding complications.
The Norwegian experience:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •Patients who receive a primary or secondary pancreas transplant, with or without a simultaneous kidney transplant (SPK).
- •Women who are of childbearing potential must have a negative serum pregnancy test at baseline.
- •Operability has to be ascertained by preoperative examination, performed by nephrologist, transplant surgeon and anaesthesiologist.
- •Signed and dated informed consent form.
排除标准
- •Evidence of systemic infection
- •Presence of unstable cardiovascular disease.
- •Malignancy < 5 years prior to entry into the trial (with the exception of adequately treated basal cell or squamous cell carcinomas of the skin).
- •Panel-reactive antibodies (PRA) > 20% or the presence of donor-specific antigens (DSA).
- •Any positive test for HBV, HBC or HIV.
结局指标
主要结局
Incidence of acute rejection episodes after pancreas- or pancreas- + kidney- transplantation
时间窗: 5 years
Compare the incidence of acute rejection episodes at 6, 12, 36 and 60 months after pancreas transplantation, between our single prospective cohort with lower CS vs a historic, retrospective control group (PTx performed during 2011-2013). The incidence of rejection is defined as the fraction of patients in which rejections episodes (one or more) have been proven by biopsies. For SPK rejection in either organ, pancreas or kidney, counts. Furthermore, we will compare the number and severity of rejection episodes in the pancreas allograft to the ones occurring in the kidney allograft (SPK), and the ones diagnosed by the duodenal segment biopsies.
Surgical complications
时间窗: 5 years
Compare the incidence of surgical complications, involving reoperations and reinterventions, between the prospective study cohort and retrospective control group.
次要结局
- Patient survival(5 years)
- Graft survival(5 years)
- Non-surgical complications(5 years)
研究者
Håkon Haugaa
Principal investigator
Oslo University Hospital