TTV-based mAnagement Of Long-term ImmunosuppreSsion in Kidney Transplantation (TAOIST)

Civil Hospices of Lyon

Status: Enrolling

Conditions: Infection; Kidney Transplantation; Cancer; Rejection

Treatments: Biological: TTV DNAemia; Biological: Biological tests; Other: EQ-5D-5L questionnaire

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06829719

69HCL23_0834

Details and patient eligibility

About

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.

Enrollment: 300 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult ≥ 18 years-old
• Recipient of a kidney allograft (third graft at most)
• 12 to 48 months post-transplantation
• Stable graft function (defined as: delta creatininemia over the previous 6 months < 20% and proteinuria < 30mg/mmol)
• On maintenance immunosuppression, which includes CNI (cyclosporin or tacrolimus) and MMF (Cellcept or Myfortic) with or without corticosteroids
• Detectable TTV DNAemia at enrollment
• No circulating DSA in solid phase assay
• Undetectable BKV DNAemia at enrollment
• Written informed consent

Exclusion criteria

• Recipient of an HLA identical graft
• Mutiple organ transplantation or functional transplant other than kidney
• Maintenance immunosuppression that includes a mTOR inhibitor, belatacept or imurel
• Presence of histological sign of active rejection (i+t > 2 and g+cpt > 2) on graft biopsy performed within 3 months before enrollment
• Uncontrolled infection at inclusion
• Infection requiring hospitalization or vaccination within 3 months before inclusion
• Pregnant, unwillingness to practice adequate contraception or patient with a pregnancy plan during 3 years of study
• Person not affiliated to a social security scheme or beneficiary of a similar scheme
• Person subject to a legal protection measure (guardianship, curatorship) or deprived of liberty

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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300 participants in 2 patient groups

TTV-guided immunosuppression

Experimental group

Description:

The adaptation of the dose of maintenance immunosuppressive drugs will be based on TTV DNAemia measured on site in the plasma of patients every 3 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).

Treatment:

Other: EQ-5D-5L questionnaire

Biological: Biological tests

Biological: TTV DNAemia

Standard Immunosuppression

Other group

Description:

TTV DNAemia will also be measured every 3 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.

Treatment:

Other: EQ-5D-5L questionnaire

Biological: Biological tests

Biological: TTV DNAemia