Novel Cooling Device for the Elimination of Warm Ischemia During Renal Transplantation

Study Overview
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Brief Summary
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Avoiding warm ischemia time during vascular anastomosis of the renal allograft is important to prevent damage. The investigators are studying a cooling device that may control the temperature of the renal allograft during transplant surgery; attempting to keep temperatures at or below 5°C for at least 60 minutes. If found effective, this could eliminate warm ischemia and potentially prevent damage to transplanted kidneys.

Detailed Description
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Warm ischemia can damage a renal allograft in many different ways often leading to early failure of the kidney transplant and sometimes even death of the transplant recipient. For this reason every effort is made to keep the allograft cold during the removal and transportation, and protocols have been developed to ensure this. Although kidneys are kept below 5°C during transportation, they re-warm rapidly during the transplant surgery. On average, kidneys are exposed to 40 or more minutes of dangerously warm temperatures during transplant surgery. To avoid damage, it is important to reduce the amount of time it is exposed to warm temperatures. Currently, there are no devices or standardized protocols available to ensure a kidney stays cold during the transplant surgery. The Principal Investigator has developed Kidney Skinn, a device that may control the temperature of the renal allograft during transplant surgery; keeping allograft temperatures at or below 5°C for at least 60 minutes. If found effective, this could eliminate warm ischemia and potentially prevent damage to transplanted kidneys. The device may also potentially provide retraction and support for the kidney during the transplant operation, making the surgery easier to perform. Additionally, the device may be found to be easily removed once the transplant is complete. A previous study was conducted with the Kidney Skinn in animals; the next step is to investigate whether the device can perform in the human clinical setting. This study will be done in 2 steps. Part A: a series of consecutive consenting patients to determine device initial safety, and Part B: a single-centre randomized-controlled pilot study of kidney transplant recipients.

Official Title
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Novel Cooling Device for the Elimination of Warm Ischemia During Renal Transplantation

Conditions
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Kidney Transplant; Complications, Delayed Graft Function

Intervention / Treatment
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* Device: Kidney cooling device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years of age at time of transplant Slated to receive a single cadaveric organ Donor declared by traditional neurological determination of death (NDD) Standard criteria donor (SCD) or Extended criteria donor (ECD) Consent obtained prior to the transplant operation Exclusion Criteria: Living donor (LD) Donor after cardiocirculatory death (DCD) Highly sensitized patients (those with Panel-reactive antibody or PRA >80%) Recipient of a previous kidney transplant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Device Feasibility
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 1:1 randomization (Part B, 40 patients). This will be preceded with a single series of 5 consecutive patients (Part A).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Surgery utilizing the Kidney Skinn cooling device<br>All patients in Part A, and those randomized to the Kidney Skinn arm in Part B, will receive transplant surgery in the traditional fashion with the exception that the renal allograft will be placed in the cooling device at the initiation of the vascular anastomosis. Cold saline irrigation flowing through the device will be used to maintain renal hypothermia for the duration for the vascular anastomosis. After the vascular clamps are released, the device will be removed. | Device: Kidney cooling device<br>* renal cooling device designed to maintain renal hypothermia at or below 5ºC for 60 minutes.<br>* Other names: Kidney Skinn;|
| No Intervention: Standard transplant surgery practice<br>Standard transplant surgery per site practice | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Device design is deemed suitable to move into the traditional feasibility stage (Part B of protocol) | The Kidney Skinn cooling device can be utilized during vascular anastomosis, and the ability of the device to maintain surface and core temperatures of transplant kidneys at <5ºC for the duration of the vascular anastomosis. | 6 months | 
| Part B: To determine the feasibility of a trial using the Kidney Skinn cooling device to usual care to ameliorate warm ischemia time during kidney transplantation | Feasibility Outcomes will include the following: Ability to randomize >60% of eligible patients >75% of patients randomized to the Kidney Skinn arm use the device 70% of patients randomized to the device (Kidney Skinn) achieve a renal allograft surface temperature of <5C for the duration of the vascular anastomosis. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who develop delayed graft function (need for dialysis in the first week after transplantation) compared with usual care | Delayed Graft function as defined by the need for dialysis in the first 7 post operative days | 7 days | 
| Difference in ischemia-reperfusion injury biomarker levels between the intervention and control groups | Urine and serum biomarkers for ischemia-reperfusion injury will be collected at specific key time points pre and post transplantation on all Part B trial participants. Specifically, urine and serum samples for unique markers of kidney injury (KIM-1 & NGAL), inflammation (TNFR1, MCP-1) and fibrosis (suPAR, YKL 40). | 7 days | 
| Serum creatinine level at discharge from initial hospitalization for transplantation | Local laboratory serum creatinine drawn per standard of care on all renal transplant recipients on day of discharge | 5-7 days | 
| Differences in achieved renal allograft surface temperature comparing the Kidney Skinn (intervention arm) versus usual care (control arm) | For each surgery, K-type 30 gauge thermocouples (each less than 0.25mm in external diameter) will be used in the renal allograft at a depth of 5 mm and 15 mm. This will be to measure surface (cortical) and core (medullary) temperatures, respectively. | 60 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kidney, transplant, warm ischemia time, delayed graft function, vascular anastomosis, renal hypothermia