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Deceased Donor Biomarkers and Recipient Outcomes (DDS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01848249
Recruitment Status : Completed
First Posted : May 7, 2013
Last Update Posted : April 9, 2020
Sponsor:
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Johns Hopkins University
Information provided by (Responsible Party):
Yale University

Tracking Information
First Submitted Date April 30, 2013
First Posted Date May 7, 2013
Last Update Posted Date April 9, 2020
Study Start Date May 1, 2010
Actual Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 21, 2017)
  • Delayed Graft Function [ Time Frame: Assessed within first week of receiving renal transplant ]
    Receipt of dialysis within the first seven days post renal transplant
  • Death-Censored Graft Failure (Overall Cohort) [ Time Frame: median of 4 years of follow-up ]
    Requirement of chronic dialysis or retransplantation after renal transplant.
Original Primary Outcome Measures
 (submitted: May 2, 2013)
  • Delayed Graft Function [ Time Frame: Assessed within first week of receiving renal transplant ]
    Receipt of dialysis within the first seven days post renal transplant
  • Death-Censored Graft Failure [ Time Frame: Within two years of receiving renal transplant ]
    Requirement of chronic dialysis or retransplantation after renal transplant.
Change History
Current Secondary Outcome Measures
 (submitted: June 21, 2017)
Graft Function (detailed cohort) [ Time Frame: median of 4 years of follow-up ]
Serum creatinine and estimated glomerular filtration rate at specified time points over a five year period.
Original Secondary Outcome Measures
 (submitted: May 2, 2013)
Graft Function [ Time Frame: Within two years of receiving renal transplant ]
Serum creatinine and estimated glomerular filtration rate at specified time points over a two year period.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Deceased Donor Biomarkers and Recipient Outcomes
Official Title Deceased Donor Urinary Biomarkers to Predict Kidney Transplant Outcomes
Brief Summary Compared to chronic dialysis, kidney transplantation provides recipients with longer survival and better quality of life at a lower cost. In order to meet increasing demands for kidney allografts, kidneys from older and sicker donors are being procured. This has led to greater discard rates of donated kidneys as well as more complications for recipients, including shorter allograft survival. Available clinical models to predict kidney allograft quality have poor prognostic ability and do not asses the degree of kidney allograft injury. However, allograft injury near the time of procurement can lead to major consequences for the transplant recipient: greater risks of delayed graft function, poor allograft function and premature loss of the transplant. Our proposal is based on the hypotheses that novel biomarkers measured in donor urine and transport media at the time of procurement can assess acute and chronic kidney injury and that distinct biomarker patterns will predict allograft survival. In collaboration with five organ procurement organizations, we will collect urine samples from consecutive deceased donors and samples of transport solution for every pumped kidney. We will measure markers of injury, repair, inflammation and fibrosis. We will determine mortality and allograft survival in all patients by linkage to the United Network for Organ Sharing (UNOS) database (Overall Cohort). Additionally, we will perform a detailed chart review of a subset of recipients (detailed cohort) and will also examine associations between biomarkers and longitudinal graft function over five years after transplant. Early, non-invasive and rapid assessment of donor kidney injury could drive better allocation decisions and potentially reduce the rates of post-transplant complications. Further, these new tools could provide a platform for clinical trials of therapies for allografts and kidney transplant recipients aimed at ameliorating allograft injury.
Detailed Description

Our study has several key processes that we have developed and tested to address our scientific aims:

  1. Enrollment

    We will collect urine samples from approximately 1600 deceased donors and approximately 600 perfusate samples from machine-pumped kidneys from participating organ procurement organizations (OPOs). We estimate that our final donor group will be comprised of 55% standard criteria donors, 25% expanded-criteria donors and 10% donors after cardiac death. Approximately, 20% of the kidneys will be discarded.

  2. Donor Data

    Donor variables come from two sources: the United Network for Organ Sharing (UNOS) database and detailed data abstraction from each OPO. The UNOS database provides data on all donors with demographics and other important clinical characteristics. The additional data collected by the OPO staff captures granular information on events surrounding donor death, which are not included in the UNOS database. These data will be available on all enrolled donors and include variables such as serial serum creatinine, nadir blood pressures, medication and vasopressor use, and machine pump parameters.

  3. Overall Recipient Cohort

    Over 2000 recipients will have received kidneys from the deceased donors in our study. The Overall Cohort will comprise all of these recipients General demographic and clinical characteristics about recipients in the Overall Cohort will come from the UNOS database. For the Overall Recipient Cohort, we will ascertain delayed graft function (DGF) through center reports to UNOS. We will ascertain allograft failure through center reports to UNOS and new episodes of wait-listing and re-transplant collected by UNOS, Recipient mortality will be ascertained through the center reports to UNOS/SRTR and through the Social Security Death Master File.

  4. Detailed Recipient Cohort

    A subset of over 1100 recipients of the Overall Cohort who had transplantation at any of our collaborating transplant centers will comprise this cohort. For the Detailed Subcohort, on-site coordinators will perform manual chart review and abstract more extensive data about each recipient including dialysis indications post-transplant, comorbidities, and specific doses of immunosuppression. For the Detailed Subcohort, we will also collect data on clinical events for up to five years after transplantation, including acute rejection and estimated glomerular filtration rate at the time of transplantation and at months 1, 3, 6, 12, 18, 24, 30, 36, 48 and 60 months after transplant.

  5. Novel biomarkers will be measured in urine and perfusate
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
((A)) Urine Samples: At time of deceased donor nephrectomy ((B)) Perfusates: At time of initiation and stopping of machine perfusion
Sampling Method Probability Sample
Study Population

The population from which our Deceased-Donor Cohort will be selected is all potential deceased organ donors located in the regions serviced by our participating organ procurement organizations (OPOs).

The recipient cohorts will be defined by the deceased donors enrolled in the study, and thus, the study population for this group is all recipients of kidneys from deceased organ donors procured in the regions serviced by our participating OPOs.

Condition
  • Deceased Donor Kidney Transplant
  • Acute Kidney Injury
  • Delayed Graft Function
  • End Stage Renal Disease
  • Graft Failure
Intervention Not Provided
Study Groups/Cohorts
  • Deceased-Donor Cohort
    We will collect urine samples from approximately 1600 deceased donors and approximately 600 perfusate samples from machine-pumped kidneys from participating organ procurement organizations (OPOs).
  • Recipient Cohort (Overall and Detailed)
    No samples will be collected from the recipients. Only clinical data and outcomes will be collected from the recipients.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: February 2, 2015)
1679
Original Estimated Enrollment
 (submitted: May 2, 2013)
1600
Actual Study Completion Date March 2020
Actual Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Donor Cohort: Appropriate informed consent for research according to OPO policies
  • Recipient Cohorts: Any recipient of at least one kidney from a deceased donor enrolled by our participating OPOs

Exclusion Criteria:

• Donor Cohort: Lack of adequate biospecimen quantity or quality as per protocol

Sex/Gender
Sexes Eligible for Study: All
Ages Child, Adult, Older Adult
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT01848249
Other Study ID Numbers 1206010465
R01DK093770-01A1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Yale University
Study Sponsor Yale University
Collaborators
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • Johns Hopkins University
Investigators
Principal Investigator: Chirag R Parikh, MD PhD Yale University
PRS Account Yale University
Verification Date April 2020