Journal Article

A multicentre, patient- and assessor-blinded, non-inferiority, randomised and controlled phase II trial to compare standard and torque teno virus-guided immunosuppression in kidney transplant recipients in the first year after transplantation: TTVguideIT

Jilma, Bernd, Bakker, Stephan J. L., König, Franz, Focosi, Daniele, Malvezzi, Paolo, Rostaing, Lionel, Rahn, Jette, Herkner, Harald, Banas, Bernhard, Pérez, Alberto Molina, Doberer, Konstantin, Vossen, Matthias, Hugo, Christian, Böhmig, Georg A., Rodriguez-Arias, David, Eller, Kathrin, Rotmans, Joris I., Bourgeois, Philippe, Gelas, Fanny, Haupenthal, Frederik, Cejka, Daniel, Budde, Klemens, Neuwirt, Hannes, Wolzt, Michael, Viklicky, Ondrej, Maggi, Fabrizio, Bond, Gregor, Banas, Miriam

2023

Overview

Background Immunosuppression after kidney transplantation is mainly guided via plasma tacrolimus trough level, which cannot sufficiently predict allograft rejection and infection. The plasma load of the non-pathogenic and highly prevalent torque teno virus (TTV) is associated with the immunosuppression of its host. Non-interventional studies suggest the use of TTV load to predict allograft rejection and infection. The primary objective of the current trial is to demonstrate the safety, tolerability and preliminary efficacy of TTV-guided immunosuppression. Methods For this purpose, a randomised, controlled, interventional, two-arm, non-inferiority, patient- and assessor-blinded, investigator-driven phase II trial was designed. A total of 260 stable, low-immunological-risk adult recipients of a kidney graft with tacrolimus-based immunosuppression and TTV infection after month 3 post-transplantation will be recruited in 13 academic centres in six European countries. Subjects will be randomised in a 1:1 ratio (allocation concealment) to receive tacrolimus either guided by TTV load or according to the local centre standard for 9 months. The primary composite endpoint includes the occurrence of infections, biopsy-proven allograft rejection, graft loss, or death. The main secondary endpoints include estimated glomerular filtration rate, graft rejection detected by protocol biopsy at month 12 post-transplantation (including molecular microscopy), development of de novo donor-specific antibodies, health-related quality of life, and drug adherence. In parallel, a comprehensive biobank will be established including plasma, serum, urine and whole blood. The date of the first enrolment was August 2022 and the planned end is April 2025. Discussion The assessment of individual kidney transplant recipient immune function might enable clinicians to personalise immunosuppression, thereby reducing infection and rejection. Moreover, the trial might act as a proof of principle for TTV-guided immunosuppression and thus pave the way for broader clinical applications, including as guidance for immune modulators or disease-modifying agents. Trial registration EU CT-Number: 2022-500024-30-00

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adult / Bacterial infections / Biomedicine / Clinical trials / Cytomegalovirus / Dosage and administration / Drug dosages / Graft Rejection - diagnosis / Graft Rejection - prevention & control / Health aspects / Health Sciences / Humans / Immunological monitoring / Immunosuppression / Immunosuppression Therapy / Immunosuppressive agents / Immunosuppressive Agents - adverse effects / Immunotherapy / Infections / Infectious diseases / Internal medicine / Kidney transplantation / Kidney Transplantation - adverse effects / Kidney transplants / Kidneys / Medicine / Medicine & Public Health / Nephrology / Non-pharmacological intervention / Organ transplant recipients / Patient outcomes / Patients / Personalised medicine / Precision medicine / Quality of Life / Severe acute respiratory syndrome coronavirus 2 / Statistics for Life Sciences / Study Protocol / Tacrolimus / Tacrolimus - adverse effects / Torque teno virus / Transplantation