TTV-based mAnagement Of Long-term ImmunosuppreSsion in Kidney Transplantation
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorHospices Civils de Lyon
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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)
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
TTV DNAemia
Biological/VaccineEvery 6 months, one sample added at the same time (7mL) of a routine laboratory analysis for TTV DNAemia
EQ-5D-5L questionnaire
Other interventionCompleted every 6 months and each time a complication of interest occurs
Biological tests
Biological/VaccineBiological tests as routine care procedure (creatinine, CNI pre-dose trough level) will be performed every 6 months
Treatment groups
600 Participants
are divided into 2 treatment groupsGroup A: TTV-guided immunosuppressionExperimental treatment 3 interventions
Group B: Standard ImmunosuppressionOther 3 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
through study completion, an average of 6 yearsSecondary outcomes
1
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 years2
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 years3
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 years4
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 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Hospices Civils de Lyon
Lead sponsor
BioMérieux
Collaborator
Source ClinicalTrials.gov