The Effect of Therapeutic Hypothermia on Deceased Donor Renal Graft Outcomes - a Randomized Controlled Trial From the Region 5 Donor Management Goals Workgroup

Renal Function Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01680744
• Other study ID #: R38OT22183
• Status: Completed
• Phase: N/A
• First received: August 21, 2012
• Last updated: December 2, 2014
• Start date: May 2012
• Est. completion date: November 2014

Study information

• Verified date: December 2014
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

To protect kidney function during the transplantation process by inducing mild hypothermia in the deceased organ donor before organs are recovered

Description:

The number of kidneys available for transplantation in the U.S. (~15,000/yr) does not meet demand (~80,000/yr). This discrepancy will likely worsen given the increasing U.S. prevalence of chronic kidney disease and is compounded by sizable organ attrition once organs have entered the donation process (25-30% attrition in Region 5). Furthermore, worsening renal function in donation after neurologic determination of death (DNDD) organ donors (an increasingly important source of allografts) is one of the strongest predictors of delayed graft function (DGF) and slow graft function (SGF) in the recipient. Both DGF and SGF are associated with decreased long-term organ survival and are of major concern to the transplant community.

To alleviate the aforementioned supply-demand imbalance, there are two major unmet needs that must be urgently addressed. First, active medical interventions that are tested prospectively to protect the organ during the donation process hold sizable potential, but remain exceedingly rare. Second, compliance with pre-defined donor management protocols to restore and stabilize deceased organ donor physiologic functions remains low across different donation service areas, despite evidence that these protocols may improve organ yield.

The goal of this proposal, therefore, is to demonstrate that (1) therapeutic hypothermia as an active medical intervention for the DNDD donor and (2) compliance with donor management protocols can substantially improve allograft function and survival.

The investigators will accomplish this goal by extending an existing research infrastructure (HRSA, R380T10586) across several donor service areas. As such, the investigators will bring together a research network and use the power of this network to properly test a simple medical intervention, therapeutic hypothermia for renal protection, in a prospective randomized single blinded trial. Therapeutic hypothermia is an established cytoprotective intervention that has been demonstrated to be highly protective of organs in select critically ill patients. By combining two of the largest donation service areas in the nation (CTDN, Northern California and OneLegacy, Southern California), the investigators will have access to approximately 10% of all organ donors in the nation. This proposal aims to randomize 500 DNDD organ donors, the biggest cohort enrolled in a prospective randomized trial.

The investigators will further leverage this network to track trial specific donor management protocols variables goals and drive tighter compliance with already established donor management protocols across all donor service areas in Region 5. This will allow the investigators to compile a large historical control cohort that will facilitate answering additional research questions with great detail. All organ procurement areas in Region 5 have confirmed their willingness to participate in this effort and contribute relevant organ donor data via a shared web-portal. Through this active participation, a secondary gain will be improved reporting of donor data and compliance with already accepted donor management goals.

Test of feasibility will be improvement in various kidney function metrics that are commonly used to evaluate organ health during the donation process. Ultimately, the investigators believe this multi-pronged approach may lead to 800 to 1000 additional kidneys that are successfully transplanted nationwide each year.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 370
• Est. completion date: November 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• > 18 years of age, deceased organ donor

Exclusion Criteria:

• < 18 years of age, not a deceased organ donor

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Death
• Deceased Organ Donor
• Hypothermia
• Mild Hypothermia
• Renal Function

Intervention

Other:
• Hypothermia
The intervention will take place after consent for donation and research has been obtained and hemodynamic stability has been achieved (mean arterial blood pressure > 60 mmHg for more than one hour without an increase in vasopressors). Organ donors in the experimental group will either be actively warmed or allowed to spontaneously reach a body temperature of 34 °C.

Locations

Country	Name	City	State
United States	University of California San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	California Transplant Donor Network

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Renal Function	The primary outcome measures are renal function as determined by creatinine and cystatin c between declaration of neurological death and organ recovery in each of the two treatment groups. Delta creatinine and terminal creatinine are important predictors of graft quality and function, as demonstrated in the present data (HRSA study and Region 5 DMG/DGF study), and will be compared between the control and treatment group.	12 hours of mild hypothermia	No