Calcineurin Inhibitor in NEuRoloGically Deceased Donors to Decrease Kidney delaYed Graft Function (CINERGY)-Pilot Trial
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 414
- 试验地点
- 9
- 主要终点
- Organ donor accrual rates
研究概览
简要总结
The investigators hypothesize that preconditioning neurologically deceased organ donors with the calcineurin inhibitor tacrolimus will improve short and long-term transplant survival without causing harm. Organ donors will be randomized to receive either 0.02 mg/kg ideal body weight (IBW) of tacrolimus single infusion or placebo before organ recovery. All corresponding recipients are enrolled and data is collected up to 7 days post-transplant to determine graft function and at 1 year to collect outcomes of vital status, re-transplantation and dialysis. The CINERGY Pilot Trial assesses feasibility for the main trial.
详细描述
Background: Organ donation saves lives, and improves quality of life for thousands of people. But organ donation falls short of expectations for some patients who suffer early graft loss. During organ donation surgery, the supply of blood with oxygen and nutrients is suspended. When restored during transplant surgery, a cascade of inflammation perturbs the newly transplanted organ -causing ischemia-reperfusion injury. When severe, it can hinder transplant function in the early post-operative period, lead to profound critical illness, increase the risks of transplant rejection and chronic disease, and reduce the transplant lifespan. Administration of tacrolimus, a calcineurin inhibitor, to neurologically deceased donors may reduce ischemia-reperfusion injury in transplant recipients.
Objectives: The CINERGY Pilot Trial will test the feasibility of comparing tacrolimus to placebo for the prevention of delayed graft function in kidney recipients and establish the foundation for a large, multi-centre randomized controlled trial (RCT).
Methods: 90 neurologically deceased kidney donors will be randomized to either tacrolimus (0.02 mg/kg) or the corresponding placebo 4-8 hours before organ recovery. To be included in the CINERGY Pilot RCT, donors will need to meet inclusion criteria. All corresponding recipients are enrolled and their data is collected in the first 7 days and at 12 months after transplantation.
Outcomes: Feasibility: Donor accrual rate and consent rate of organ recipients. Safety: acute kidney injury, hyperkalemia and anaphylaxis in donors and recipients. Clinical: graft function within 7 days in all recipients, vital status, re-transplantation and need for dialysis at 12 months.
Relevance: This pilot study will inform the feasibility and design of a larger trial. Moreover, the CINERGY Pilot RCT will pave the way for future trials linking organ donation and transplantation across Canada.
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
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥18 years of age;
- •Neurologically deceased;
- •Consent for deceased organ donation;
- •All organ recipients have been identified;
- •≥ 1 kidney allocated to a recipient.
排除标准
- •Known hypersensitivity to tacrolimus or polyoxyl 60 hydrogenated castor oil;
- •One or more organs allocated to a non-participating transplant program;
- •Unlikely access to study drug (e.g., due to supply issues, or pharmacist availability);
- •One or more organ recipients has not agreed to receive an organ from a donor participating in the study;
- •One or more organs are allocated to a recipient under the age of 18;
- •A transplant physician has judged that donor tacrolimus will be unsuitable for an intended recipient.
- •Recipient Inclusion Criteria
- •Organ/Transplant graft originated from a donor enrolled in this study.
- •No exclusion criteria.
研究组 & 干预措施
Tacrolimus
Tacrolimus 0.02 mg/kg ideal body weight 4-8 hours before organ recovery
干预措施: Tacrolimus (Drug)
Placebo
0.9% sodium chloride 4-8 hours before organ recovery
干预措施: Placebo (Drug)
结局指标
主要结局
Organ donor accrual rates
时间窗: 6 to 12 months after the beginning of the trial
One primary objective of this pilot study is to determine if a national multi-centre placebo randomized controlled trial (RCT) will be feasible with respect to: organ donor accrual.
Recipient consent rate
时间窗: 6 to 12 months after the beginning of the trial
Another primary objective of this pilot study is to determine if a national multi-centre placebo controlled RCT will be feasible with respect to the consent rates of organ recipients. Recipient consent rates will be assessed during analysis, analyzing the rate and reasons for non-enrolment.
次要结局
- Percentage of recipients with hyperkalemia(Within 7 days post transplant)
- Percentage of donors with cardiac arrhythmia associated with tacrolimus infusion(Within 4 hours after the initiation of study drug infusion)
- Percentage of liver recipients with early graft function(Within 7 days post transplant)
- Unexpected adverse events(Within 7 days post transplant)
- Correlation between two methods for obtaining survival status(12 months post transplant)
- Percentage of recipients with anaphylaxis(Within 7 days post transplant)
- Graft survival(12 months post transplant)
- Recipients requiring dialysis(12 months post transplant)
- Percentage of donors with anaphylaxis(Within 4 hours after the initiation of study drug infusion)
- Percentage of donors with acute kidney injury (AKI)(Within 4 hours after the end of the study drug infusion)
- Percentage of donors with hyperkalemia(Within 4 hours after the end of the study drug infusion)
- Percentage of donors hypertension during tacrolimus infusion(Within 4 hours after the initiation of study drug infusion)
- Percentage of recipients with acute kidney injury(Within 7 days post transplant)
- Percentage of heart recipients with severe primary graft dysfunction(Within 1 days post transplant)
- Recipient serum tacrolimus levels(Within 7 days post transplant)
- Recipient survival(12 months post transplant)
- Percentage of lungs recipients with severe primary graft dysfunction(Within 3 days post transplant)
- Percentage of kidney recipients with delayed graft function(Within 7 days post transplant)
- Percentage of pancreas recipients with delayed graft function(At hospital discharge, an average of 7 days)