Prospective, Randomized, Double-Blind, Double-Dummy, Multicenter Trial to Assess Safety of Single Dose vs. Traditional Administration of Thymoglobulin Induction for Renal Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 99
- 试验地点
- 8
- 主要终点
- Composite Endpoint of 5 Components: Fever, Hypoxia, Hypotension, Cardiac Events, and Delayed Graft Function
研究概览
简要总结
In a non-blinded pilot study conducted at the University of Nebraska Medical Center, evidence was found that a single large dose of Thymoglobulin on the day of kidney transplantation produced better kidney function than the standard dosing plan, when the same amount is divided into smaller doses on 4 days. This new study repeats that dose comparison, but with double-blinding and at multiple transplantation centers.
详细描述
This study is designed to confirm the one-year safety of single-dose rabbit anti-thymocyte globulin induction at kidney transplantation, compared to the conventional administration of the same overall dose divided into four smaller doses across four days. Two randomized groups of kidney transplant recipients will be each administered the drug Thymoglobulin according to a different dosing regimen. The control group will receive the usual and traditional regimen of a total of 6 mg/Kg divided into 4 doses, 1 on the day of transplantation and 1 each day on the next 3 days. The experimental group will receive the same total Thymoglobulin dose, 6 mg/Kg, but entirely on the day of transplantation.
The study will be double-blinded, with placebo doses of Thymoglobulin administered as needed to enrollees in the experimental group. Enrollment is targeted at 165, with 150 subjects needed to complete the study for adequate evaluation.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Subject capable of giving written informed consent, with end-stage kidney disease, who is a suitable candidate for primary kidney transplantation
- •Male or female subject who has reached legal age in the state where they reside and is at least 18 years of age
- •Deceased or living donors
- •Compatible ABO blood type
- •Expanded-criteria donor (ECD) kidneys with a donor grade score of ≤ 25 (as developed by Nyberg, et al.)
- •If Kidneys are pumped, they must meet the following pumping parameters: resistance <0.35 with a flow rate of >60 ml/min.
排除标准
- •Recipient age >65 years
- •PRA >50%, or donor-specific antibody
- •CIT >30 hours
- •Re-transplant patients
- •Multi-organ transplant recipients (example: kidney/pancreas or kidney/liver)
- •Renal transplant recipients planned for future pancreas transplantation
- •Current unstable cardiovascular disease or history of myocardial infarction within the previous 6 months
- •Current malignancy or history or malignancy (within the previous 5 years) with the exception of non-metastatic basal or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix that has been treated successfully.
- •Hepatitis B and C recipients or active liver disease
- •HIV positive recipients
- •Primary disease requiring treatment with steroids after transplantation
- •Expanded-criteria donor kidneys (current UNOS criteria) with a donor grade score of > 25
- •Donation after cardiac death (DCD) donors
- •Dual adult kidneys
- •Recipients of pediatric (age <12 years) unilateral or en-bloc kidneys
- •Previous treatment with rATG
- •Known hypersensitivity, extensive exposure, or allergy to rabbits
- •Any condition that in the investigator's opinion may compromise study participation (e.g., history or likelihood of non-compliance with immunosuppression regimen, protocol visits, tests, and studies)
- •Relative Exclusion Criteria:
- •Patients with a BMI > 37 should be considered on an individual basis based on overall health and body habitus.
结局指标
主要结局
Composite Endpoint of 5 Components: Fever, Hypoxia, Hypotension, Cardiac Events, and Delayed Graft Function
时间窗: During first 7 days after kidney transplantation
The composite endpoint components and definitions are: * Fever: Body temperature ≥ 38.5˚C. * Hypotension: After rATG initiation, systolic blood pressure ≤ 90 mmHg requiring de novo treatment with vasopressors. * Hypoxia: During transplantation surgery, increase in FiO2 to ≥ 60% following rATG initiation. Following transplantation, starting in recovery room, FiO2 ≥ 50% or nasal cannula delivering ≥ 3 liters, either singly or combined, for \> 12 hours out of a 24 hour period. * Cardiac events: Myocardial Infarction, clinically significant dysrhythmia (atrial fibrillation, atrial flutter, ventricular fibrillation and ventricular tachycardia) * Delayed graft function (DGF): Requirement for dialysis within 7 days of transplantation
次要结局
- Acute Kidney Rejection(12 months post-transplantation)
- Patient Survival(12 months post-transplantation)
- Incomplete Thymoglobulin Infusion(First 7 days post-transplantation)
- Graft Survival(12 months post-transplantation)
- Kidney Function(12 months post-transplantation)
研究者
R. Brian Stevens, MD, PhD, FACS, FAST
Professor of Surgery and Graduate Studies and Director, Transplantation Division
Wright State University