An Investigator-initiated, Pragmatic, Registry-based, Multi-centre, Double-blind, Randomised Controlled Trial Evaluating the Effect of Plasmalyte Versus 0.9% Saline on Early Kidney Transplant Function in Deceased Donor Kidney Transplantation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 808
- 试验地点
- 18
- 主要终点
- The proportion of participants with Delayed Graft Function
研究概览
简要总结
End-stage kidney disease (ESKD) is a significant, expensive health problem. Kidney transplantation improves survival, quality of life, and is much cheaper than dialysis treatment for ESKD. However sometimes kidney transplants from a deceased donor function poorly after surgery, and a period of continued dialysis is needed, a condition known as delayed graft function (DGF). In addition to complicating recovery, DGF can adversely affect long-term kidney function and the health of the recipient.
Intravenous fluids given during and after transplantation (usually 0.9% sodium chloride or saline) are critical to preserve kidney transplant function, but there is evidence that 0.9% saline may not be the safest fluid to use due to its high chloride content.
BEST Fluids is a randomised controlled trial that aims to find out whether using a balanced low-chloride solution - Plasma-Lyte 148® - as an alternative to normal saline in deceased donor kidney transplantation, will improve kidney transplant function, reduce the impact of DGF, and improve long-term outcomes for patients.
详细描述
End-stage kidney disease is a significant public health problem worldwide, and its treatment imposes a high healthcare burden and cost. Kidney transplantation is considered the best treatment for ESKD, offering improved survival and quality of life at significantly lower cost that dialysis. However, many kidney transplants fail prematurely due in part due to injury sustained at the time of transplantation. Delayed graft function (DGF), i.e. the requirement for dialysis early after transplantation, affects approximately 30% of deceased donor kidney transplants, and increases the risk of graft failure and mortality.
Intravenous fluids are a critical, albeit inexpensive, aspect of care that impacts early transplant function with normal (0.9%) saline the current standard care at most centres. However, normal saline may in fact be harmful in the setting of kidney transplantation due to its high chloride content relative to plasma, causing metabolic acidosis, acute kidney injury and thus potentially increasing the risk of DGF. Utilising a balanced low-chloride crystalloid solution such as Plasma-Lyte 148® (Plasmalyte) as an alternative to 0.9% saline may therefore improve outcomes after kidney transplantation.
The BEST-Fluids study is an investigator-initiated, pragmatic, registry-based, multi-centre, double -blind randomised, controlled trial. The primary objective of the study is to evaluate the effect in deceased donor kidney transplant recipients of intravenous therapy with Plasmalyte versus 0.9% saline, commencing pre-operatively and continuing until intravenous fluids are no longer required or 48 hours post-transplant (whichever is earliest), on DGF, defined as the requirement for dialysis in the first seven days post-transplant.
Patients admitted for a deceased donor kidney transplant at participating centres will be invited to participate in the study prior to transplant surgery. Following informed consent, participants will be randomised to receive either blinded Plasmalyte or blinded 0.9% saline for all intravenous fluid therapy purposes until 48 hours post-transplant. The volume and rate of fluid therapy will be determined by treating clinicians; all other treatments will be as per local standard of care. Participants will be enrolled, randomised and followed up using ANZDATA, the Australia & New Zealand Dialysis & Transplant Registry.
The trial was prospectively registered with Australia New Zealand Clinical Trials Registry (ANZCTR) on 08/03/2017 (ACTRN12617000358347).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult or child with End-Stage Kidney Disease, of any cause, on maintenance dialysis, or who has pre-dialysis stage 5 chronic kidney disease with an estimated Glomerular Filtration Rate of <15 mL/min/1.73m2, AND
- •Planned deceased donor kidney transplant from a brain-death (DBD) or circulatory-death (DCD) organ donor within 24 hours, AND
- •Written informed consent, or consent given by their parent or guardian (if age <18), or other authorised person
排除标准
- •Planned live donor kidney transplant (except where this is cancelled in favour or transplantation from a deceased donor)
- •Planned multi-organ transplant (dual or en-bloc kidney transplants are not excluded)
- •Children of weight <20 kg, or a child that the treating physician believes should not be included in a study of blinded fluids due to their small body size
- •Known hypersensitivity to the trial fluid preparations or packaging
研究组 & 干预措施
Plasma-Lyte 148 (approx. pH 7.4) IV Infusion
Plasma-Lyte 148 (approx. pH 7.4) IV Infusion intravenous fluid therapy will be used for all maintenance, replacement and resuscitation purposes from randomization onwards until 48 hours post-transplant, or until fluid therapy is no longer required, if earlier.
干预措施: Plasma-Lyte 148 (approx. pH 7.4) IV Infusion (Drug)
0.9% SODIUM CHLORIDE 9g/L injection BP
0.9% saline intravenous fluid therapy will be used for all maintenance, replacement and resuscitation purposes from randomization onwards until 48 hours post-transplant, or until fluid therapy is no longer required, if earlier.
干预措施: 0.9% SODIUM CHLORIDE 9g/L injection BP (Drug)
结局指标
主要结局
The proportion of participants with Delayed Graft Function
时间窗: 7 Days
Delayed Graft Function defined as receiving treatment with any form of dialysis in the first seven days after transplant
次要结局
- Aggregate urine output(Until day 2 post-transplant)
- Healthcare resource use(12 months)
- Creatinine reduction ratio from day 1 to day 2 post-transplant(Day 1 to Day 2 post-transplant)
- Incidence of serum potassium greater than or equal to 5.5 mmol/L(First 48 hours post-transplant)
- Treatment for hyperkalaemia(First 48 hours post-transplant)
- Incidence of significant fluid overload(Baseline to day 2)
- Health-related quality of life(Baseline, day 7, day 28, week 12, week 26, and week 52)
- Number of acute rejection episodes(12 months)
- Length of hospital stay(12 months)
- Early Kidney Transplant Function(a. Duration of Delayed Graft Function - 12 Weeks; b. Rate of recovery of kidney transplant graft function - 2 Days)
- Peak potassium level(First 48 hours post-transplant)
- Requirement for inotropic support (use of vasopressors or other drugs to maintain adequate blood pressure)(Intra- and post-operatively to Day 2)
- Number of renal transplant biopsies(First 28 days post-transplant)
- Death from all causes(Up to 52 weeks)
- Cost-effectiveness(12 months)
- Number of dialysis sessions(First 28 days post-transplant)
- Total duration of dialysis(12 Weeks)
- Reduction in serum creatinine of greater than or equal to 10%(First 7 days post-transplant)
- Serum creatinine trends over 52 weeks(12 months)
- Graft survival(12 months)
- Graft function(4, 12, 26 and 52 weeks)