Staged Kidney Transplantation During Combined Heart/Kidney Transplantation

Overview

The primary purpose of this study is to evaluate the safety and efficacy of ex vivo machine perfusion with staged implantation of kidney allografts during combined heart/kidney transplantation.

Detailed description

Combined heart and kidney transplantation (H/KTx) is the treatment of choice for patients with concomitant heart failure and chronic- or end-stage kidney disease. H/KTx presents a logistical challenge, often involving multiple surgical teams and requiring extended operative time to perform both heart and kidney transplants. Additionally, during heart transplantation, recipients require anticoagulation and multiple inotropes and vasopressors to support heart function early after implantation. While necessary, these may be detrimental to the newly implanted kidney allograft, potentially contributing to vasoconstriction, bleeding, hypotension, and worsening ischemia-reperfusion injury. Unfortunately, delaying implantation leads to extended cold ischemic time which also may be detrimental to the graft. Delayed graft function (DGF) of the kidney allograft is defined as the need for dialysis in the first seven days after transplantation and has been shown to be an important risk factor for graft loss following H/KTx. Ultimately, H/KTx requires balancing recipient stability with cold ischemic time to optimize kidney graft function. New perfusion technology adds oxygenation to the perfusate of the kidney allograft, thereby resuscitating the organ during preservation and reducing ischemia-reperfusion injury. This study seeks to evaluate the safety and efficacy of planned delayed implantation to allow for improved recipient stability and coagulopathy, while using hypothermic oxygenated machine perfusion (HOPE) for kidney preservation.

Interventions

• Other Planned delayed implantation of kidney allograft with ex vivo machine perfusion kidney preservation.
  During combined heart and kidney transplantation, heart and kidney allografts may be implanted during a single operative event, or with delayed kidney implantation in a second operative event. Timing of the delay is often determined by recipient stability and kidney availability; however, clinicians must balance recipient factors with accumulating cold ischemic time of the kidney allograft. This study uses hypothermic oxygenated machine perfusion to reduce ischemic injury to the kidney allograft

Primary outcome measures

• Incidence of delayed graft function (DGF) of the kidney allograft [Time frame: 7 days]
• Number of patients with at least one adverse event [Time frame: 90 days]

Secondary outcome measures (9)

• Number of Patients with Heart Primary Graft Dysfunction [Time frame: 24 hours]
• 6 Month Kidney allograft function [Time frame: 6 months]
• 12-month Kidney Allograft Function [Time frame: 12 months]
• intensive care unit length of stay [Time frame: 1 year]
• Hospital Length of Stay [Time frame: 1 year]
• Number of readmissions [Time frame: 90 days]
• Incidence of Kidney Allograft Rejection [Time frame: 1 year]
• Number of patients with Heart allograft rejection [Time frame: 1 year]
• 36-month kidney allograft function [Time frame: 36 months]

Eligibility criteria

Inclusion criteria

• Adult patients (18 years or older) undergoing combined heart and kidney transplantation at Cedars-Sinai Medical Center.

Exclusion criteria

• Patients who undergo simultaneous heart/kidney transplantation in a single operative event due to medical necessity will be excluded.
• Patients with medical records flagged as "break-the-glass" or "research opt-out" within the center's electronic health record.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Cedars-Sinai Medical Center — Los Angeles

Publications

• Kobashigawa J, Zuckermann A, Macdonald P, Leprince P, Esmailian F, Luu M, Mancini D, Patel J, Razi R, Reichenspurner H, Russell S, Segovia J, Smedira N, Stehlik J, Wagner F; Consensus Conference participants. Report from a consensus conference on primary graft dysfunction after cardiac transplantation. J Heart Lung Transplant. 2014 Apr;33(4):327-40. doi: 10.1016/j.healun.2014.02.027. Epub 2014 Mar PMID 24661451
• Jochmans I, Brat A, Davies L, Hofker HS, van de Leemkolk FEM, Leuvenink HGD, Knight SR, Pirenne J, Ploeg RJ; COMPARE Trial Collaboration and Consortium for Organ Preservation in Europe (COPE). Oxygenated versus standard cold perfusion preservation in kidney transplantation (COMPARE): a randomised, double-blind, paired, phase 3 trial. Lancet. 2020 Nov 21;396(10263):1653-1662. doi: 10.1016/S0140-673 PMID 33220737
• Lutz AJ, Nagaraju S, Sharfuddin AA, Garcia JP, Saleem K, Mangus RS, Goggins WC. Simultaneous Heart-kidney Transplant With Planned Delayed Implantation of the Kidney Graft After Ex Vivo Perfusion. Transplantation. 2023 Sep 1;107(9):2043-2046. doi: 10.1097/TP.0000000000004661. Epub 2023 Jun 5. PMID 37271866
• Ruzza A, Czer LS, Trento A, Esmailian F. Combined heart and kidney transplantation: what is the appropriate surgical sequence? Interact Cardiovasc Thorac Surg. 2013 Aug;17(2):416-8. doi: 10.1093/icvts/ivt172. Epub 2013 Apr 24. PMID 23615433

Identifiers

NCT: NCT06877169 · STUDY00003743

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗