Transplantation of Uncontrolled DCD Kidneys REconditioned by a Novel Ex-VIVo Perfusion MEthod (REVIVEME)

January 19, 2023 updated by: Michael Olausson, Sahlgrenska University Hospital, Sweden

Single Center, First-In-Man, Proof-of-Concept Study: Transplantation of Uncontrolled DCD Kidneys REconditioned by a Novel Ex-VIVo Perfusion MEthod - The REVIVEME Trial

Eight patient will be transplanted with kidneys from donors dying after uncontrolled circulatory arrest (uDCD), with prolonged warm ischemia (up to 4,5 hours), preserved by a new method based on removal of fibrinogen/fibrin in the capillary systems, leading to an effective oxygenation of the tissue using an ex-vivo hospital manufactured perfusion device, minimizing the risk for ischemia-reperfusion injury (I/R-I) after kidney transplantation.Each patient will be studied for three months, with long-term follow-up data collected at 6 and 12 months

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

In a large animal model we have shown that kidneys from uDCD donors, subjected to 4½ hours of warm ischemia time (WIT) can be safely reconditioned to normal function, without the use of advanced cardiopulmonary resuscitation (aCPR), extracorporeal circulation, or use of anticoagulants given to the donor. Furthermore, kidneys from uDCD, treated according to the new method, can safely be transplanted into pigs, having normal renal function (measured with creatinine and iohexol-clearance) at the three-month follow-up. Toxicity studies in pigs, conclude that minimal amounts of drugs are transferred at the transplantation, most of the components being reduced during the ex-vivo process, showing levels transferred to the recipient being very low. The renal histology was close to normal in biopsies taken from the kidneys surviving three months, without signs of fibrosis or glomerulosclerosis. Our research is supported by data from other labs. In short - our new method means that we prevent the I/R-I caused by obstruction of the arterial flow, with hypoxia as result. Normally, at reperfusion, fibrin in abundance will result in clot formation when activated platelets and red blood cells (RBCs) arrive. Consequently, kidneys will tolerate a substantially longer WIT than if the capillaries would have been occluded with hypoxia as result. Based on our large animal data, we have strong reasons to believe that the proposed new method significantly will reduce the frequency of delayed graft function (DGF), increase the quality of the renal grafts, and increase the donor pool for successful kidney transplantations.

The present study protocol describes a first-in-human trial, in which uDCD-kidneys are reconditioned and preserved using this new perfusion method and then transplanted to patients on the waiting list for diseased donors. The purpose of the present clinical proof-of-concept (PoC) trial is to show that a novel method for preservation of donated kidneys with prolonged warm ischemia time, developed in pigs, can be safely transferred to transplantations of uDCD-kidneys in humans.

Injection time of Solution A is defined as the start of the reconditioning phase. Solution A is injected into the renal arteries of the explanted kidneys after closing the renal veins with a vascular clamp. A clamp is placed on the arteries after injection of Solution A. After 30 to 210 min, a second dose of Solution A is given, followed by Solution B 15 min later, injected into the renal arteries. During the next 15 -30 minutes, vascular adapters for the aorta patches/arteries and nipples for the ureters are mounted. The kidneys are moved to the organ chamber in a hospital manufactured medical technical product (MTP) and connected to the perfusion circuit. The oxygenated perfusion is started at 24 °C at a pressure of 30 mmHg. The pressure is gradually increased with 5 mmHg every minutes up to a maximum of 80 mmHg, to allow for the capillaries to be cleared of fibrin clots, after which temperature is decreased to 15 °C and the pressure to 20mmHg. After three hours, washed RBCs (with low platelet counts) are added, temperature is raised to 25 mmHg and temperature to 28-32 °C. Oxygenated perfusion is continued, with the perfusate passing through adsorbers. Vascular resistance and flow are monitored for during the whole medical device perfusion process. After final evaluation and assessment of the kidneys by the user, temperature is decreased to 15 °C and pressure to 20 mmHg, with perfusion continuing until kidney is disconnected and retrieved from the organ chamber and assessed for viability for transplantation by the user prior to being transplanted.

Study Type

Interventional

Enrollment (Anticipated)

8

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Both sexes
  • Age 18 - 65
  • First-time transplant
  • ABO blood-group identical
  • Living within 4 hours from transplant site
  • Written consent

Exclusion Criteria:

  • Human Leukocyte Antigen (HLA) antibodies and/or preformed donor specific antibodies (DSA)
  • Total ischemia time of > 16 hours
  • Multi organ transplant recipients or previously transplanted
  • ABO-incompatible or positive complement-dependent crossmatch (CDC X-match)
  • Contraindicating medical condition
  • Contraindicating malignancy
  • Recent drug abuse
  • Non-adherent or difficulties understanding the protocol
  • Known risk factors for technical surgical complications (i.e. serious arteriosclerosis and or obesity)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: uDCD arm
Patients enroled in the study will receive a kidney from a uDCD donor, after the kidney has been subjected to a reconditioning procedure, preventing ischemia/reperfusion-injury, confirming large animal data using the same protocol.
Other: uDCD treatment
Thrombolytic treatment/prevention ex-vivo to kidneys procured from patients after circulatory arrest

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety - Serious Adverse Events
Time Frame: Three months post transplantation
Occurrence of serious adverse events, Clavien-Dindo IV-V grade complications, including primary none function
Three months post transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sahlgrenska University Hospital, Sweden

Investigators

  • Study Chair: Niclas Kvarnström, MD, PhD, Västra Götalandsregionen - SU - Sahlgrenska

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

August 21, 2023

Primary Completion (Anticipated)

August 31, 2024

Study Completion (Anticipated)

December 31, 2024

Study Registration Dates

First Submitted

January 19, 2023

First Submitted That Met QC Criteria

January 19, 2023

First Posted (Estimate)

January 30, 2023

Study Record Updates

Last Update Posted (Estimate)

January 30, 2023

Last Update Submitted That Met QC Criteria

January 19, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GOT

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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