Long-term outcomes in kidney transplantation remain a significant challenge, as complications such as donor-specific antibodies (DSA), antibody-mediated rejection, infections, and cancer increasingly threaten graft and patient survival over time. The development of non-invasive biomarkers to guide the management of therapeutic immunosuppression beyond the first year post-transplantation is therefore a crucial unmet need. Torque Teno Virus (TTV), a non-pathogenic virus with a high prevalence worldwide, has emerged as a promising biomarker in this context. Its replication inversely reflects immune control by T cells, correlating with the depth of therapeutic immunosuppression. Additionally, its slow replication kinetics make TTV DNAemia a useful marker for evaluating patient adherence to immunosuppressive treatments. The TAOIST study tests whether longitudinal monitoring of TTV DNAemia every three months, starting from the second year after transplantation, can guide the personalization of immunosuppressive therapy. The primary endpoint is the time to the first occurrence of complications linked to inadequate immunosuppression, including dnDSA, biopsy-proven rejection, infection, cancer, or graft loss. Secondary objectives include evaluating the acceptability of TTV DNAemia among healthcare professionals and assessing its cost-effectiveness compared to standard care. An ancillary objective examines the link between TTV DNAemia and the immunosuppressant possession ratio (IPR) to explore its potential as a marker of treatment adherence.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
SINGLE
Enrollment
300
Every 3 months, one sample added at the same time (7mL) of a routine laboratory analysis for TTV DNAemia
Completed every 6 months and each time a complication of interest occurs
Biological tests as routine care procedure (creatinine, CNI pre-dose trough level) will be performed every 6 months
Service de Néphrologie-Transplantation-Dialyse I Hôpital Pellegrin I - CHU Bordeaux
Bordeaux (France), France
NOT_YET_RECRUITINGService de transplantation, néphrologie et immunologie clinique Hospices Civils de Lyon, Hôpital Edouard Herriot
Lyon, France
RECRUITINGService de Néphrologie, Dialyse et Transplantation Rénale Nouvel Hôpital Civil
Strasbourg (france), France
NOT_YET_RECRUITINGDépartement de Néphrologie et Transplantation d'Organes Hôpital Rangueil - CHU de Toulouse
Toulouse (France), France
NOT_YET_RECRUITINGCompare the time from inclusion to first complication of inadequate immunosuppression between the experimental group, whose treatment is tailored on quarterly TTV viral load results, and the control group.
Time from inclusion to occurrence of the first complication of inadequate immunosuppression: development of dnDSA, biopsy-proven rejection, infection, cancer, graft loss. Patients lost to follow-up or died without an event before will be right censored at this date.
Time frame: through study completion, an average of 6 years
Proportion of patients with at least one complication of inadequate immunosuppression between the experimental and control groups at 36 months
Percentage of patients with at least one complication of inadequate immunosuppression during the 36 months of follow-up.
Time frame: through study completion, an average of 6 years
Compare the rate of complications of inadequate immunosuppression between patients in the experimental and control groups.
Number of complications of inadequate immunosuppression/patient/month of follow-up
Time frame: through study completion, an average of 6 years
Describe the nature and timing of various complications of inadequate immunosuppression in the experimental and control groups.
Percentage of patients (at 36 months) and time to first complication for each of the complications of interest: development of dnDSA, biopsy-proven rejection, infection, cancer, graft loss.
Time frame: through study completion, an average of 6 years
Compare the proportion of patients with adequate immunosuppressive therapy between the experimental and control groups.
Percentage of patients with TTV viral load between 3.8 and 5.1 log cp/ml at the majority (\>6/12) of quarterly routine controls.
Time frame: through study completion, an average of 6 years
Compare the proportion of quarterly systematic checks of TTV DNAemia in the target between patients in the experimental and control groups.
Percentage of quarterly routine TTV viral load tests between 3.8 and 5.1 log cp/ml.
Time frame: Every 3 months
Model the impact of variations in dose and residual rates (pre-dose trough levels or AUC) of the various immunosuppressive drugs on TTV viral load.
Joint analysis of the evolution of dose variations, residual immunosuppression rates of immunosuppressive drugs and TTV viral load.
Time frame: every 3 months
Evaluate how nephrologists and biologists feel about using the new test in clinical practice.
Questionnaires specific to each sub-populations (nephrologists and biologists) using open-ended questions and Likert scale-coded responses.
Time frame: 6th year
Assess the cost-effectiveness of the intervention compared to standard care at 36 months from the French Health care System perspective
Cost-effectiveness ratio (ICER) is defined as the difference in cost between the intervention and the standard care, divided by the difference in their effect (QALY).
Time frame: through study completion, an average of 6 years
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