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| Name | Class |
|---|---|
| BioMérieux | INDUSTRY |
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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 six 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TTV-guided immunosuppression | Experimental | The adaptation of the dose of maintenance immunosuppressive drugs will be based on TTV DNAemia measured on site in the plasma of patients every 6 months (at distance of an infection or a vaccination). The physicians will be free to change the dose of calcineurin inhibitors (CNI) and/or the mycophenolate mofetil (MMF) to maintain TTV DNAemia between 3.8 and 5.1 log10 cp/mL as long as the trough levels remain between 3-12 ng/mL for tacrolimus (50-250 ng/mL for cyclosporin) and the daily dose of MMF is comprise between 250 and 1500 mg bid for Cellcept (180 and 900 mg for Myfortic). |
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| Standard Immunosuppression | Other | TTV DNAemia will also be measured every 6 months but the results will not be communicated to the physicians. Instead, the adaptation of the dose of maintenance immunosuppressive drugs will be performed according to the current standard of care: i) the dose of the CNI will be adapted to maintain the trough levels, monitored in the circulation every 3 month, between 5-10 ng/mL for tacrolimus (75-150 ng/mL for cyclosporin) and ii) the dose of MMF will be adjusted to maintain the AUC, measured every year, between 30-60 h.mg/L. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TTV DNAemia | Biological | Every 6 months, one sample added at the same time (7mL) of a routine laboratory analysis for TTV DNAemia |
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| Measure | Description | Time Frame |
|---|---|---|
| Compare the time from randomization 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 randomization 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. | through study completion, an average of 6 years |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | through study completion, an average of 6 years |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Olivier THAUNAT, Professor MD, PhD | Contact | +334.72.11.69.28 | olivier.thaunat@chu-lyon.fr |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Service de Néphrologie-Transplantation-Dialyse I Hôpital Pellegrin I - CHU Bordeaux | Not yet recruiting | Bordeaux (France) | 33000 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41323957 | Derived | Doberer K, Kapps S, Haupenthal F, Bond G. Immune Monitoring Goes Viral - Torque Teno Virus for Immunologic Risk Stratification After Kidney Transplantation. Transpl Int. 2025 Nov 14;38:15074. doi: 10.3389/ti.2025.15074. eCollection 2025. |
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| ID | Term |
|---|---|
| D007239 | Infections |
| D009369 | Neoplasms |
| D012059 | Rejection, Psychology |
| ID | Term |
|---|---|
| D012919 | Social Behavior |
| D001519 | Behavior |
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Prospective, interventional, multicentric, open-label, parallel group, superiority randomized controlled trial.
Kidney transplant recipients from the 4 enrollment centers will be randomly assigned with a 1:1 allocation into experimental and control groups between 12- and 48-months post-transplantation, and prospectively followed for 36 months for the occurrence of a complication due to inadequate (over or under) immunosuppression.
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TTV DNAemia will be measured every 6 months for all patients but the results will not be communicated to the physicians for patients from the control group.
| EQ-5D-5L questionnaire | Other | Completed every 6 months and each time a complication of interest occurs |
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| Biological tests | Biological | Biological tests as routine care procedure (creatinine, CNI pre-dose trough level) will be performed every 6 months |
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| 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 |
| 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. | 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. | 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. | Every 6 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. | every 6 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. | 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). | through study completion, an average of 6 years |
| Service de transplantation, néphrologie et immunologie clinique Hospices Civils de Lyon, Hôpital Edouard Herriot | Recruiting | Lyon | 69003 | France |
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| Service de Néphrologie, Dialyse et Transplantation Rénale Nouvel Hôpital Civil | Not yet recruiting | Strasbourg (france) | 67091 | France |
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| Département de Néphrologie et Transplantation d'Organes Hôpital Rangueil - CHU de Toulouse | Recruiting | Toulouse (France) | 31059 | France |
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