TTV Viral Load in Heart Transplant Recipients

Study Overview
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Brief Summary
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This prospective, multicenter, non-interventional trial aims to study the association between TTV viral load and the occurrence of rejection or infection during the first year after transplantation. The TTV viral loads, taken once a month during the first year after the transplant, will be measured at the end of the study.

Detailed Description
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TTV (Torque Teno Virus) is a ubiquitous virus that is not associated with any disease. A correlation exists between the level of TTV replication and the subject's immunocompetence: weak or non-existent in immunocompetents, very high in immunocompromised patients. In heart transplant patients, pharmacological dosing of immunosuppressants prevents their toxic manifestations but is not correlated with individual immune competence. Only clinical manifestations of overdose (infections) or under dosage (rejections) currently allow optimization of immunosuppressants. A predictive biomarker of these clinical manifestations upstream of their appearance would revolutionize the management of these patients. The TTV fulfills the conditions to be an ideal biomarker: classic blood sampling, possible follow-up in all patients, low cost, carrying out the analysis on already existing molecular biology platforms, reproducibility of inter- and intra-laboratory results, defined thresholds for the reliable interpretation of the results. We believe that this marker will provide the clinician with a useful tool for the management of immunosuppressants and the patient with personalized medicine which will allow their management to be individualized. If this study confirms the expected results, then it will allow, secondly, the setting up of interventional studies to validate the TTV viral load as a biomarker, and a tool for piloting immunosuppressive treatment. The TTV viral load of heart transplant patients will be follow during the first year after transplantation. A tube of blood will be taken during the transplant and then once or twice a month. Samples will be taken at the same time as those taken as part of standard care. The TTV viral load will be measured at the end of the study. The occurrence of events of interest (infections and rejections) will be collected at each corresponding visit.

Official Title
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Association Between TTV Viral Load and the Occurrence of Infections and Rejection in Heart Transplant Recipients

Conditions
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Heart Transplant Rejection, Heart Transplant Infection, Virus

Intervention / Treatment
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* Other: Collection of EDTA blood sample (5 to 7 ml)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Heart transplant only First transplant Patient not having objected to carrying out the research Affiliated to a French Health Insurance system. Exclusion Criteria: Patient transplanted from more than one solid organ Patient who has already been transplanted before Patient under guardianship or curatorship Patient under legal protection Pregnant or breastfeeding woman

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| All the patients included in the study<br>50 patients, at least 18 years old, first heart transplant | Other: Collection of EDTA blood sample (5 to 7 ml)<br>* For all the patients included in the study, the samples to measure the viral load will be taken during the transplantation, then at each of the consultations planned as part of the usual care during the first year post-transplant (at minimum once and maximum twice a month). These samples will be taken at the same time as those taken as part of standard care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite outcome : Infections or Rejections | The primary endpoint is a composite endpoint defined as time to infections (first and recurrences) or rejections (first and recurrences) within the 12 months post-transplant: Infections are defined as viral Infections , bacterial and parasitic infections requiring the establishment of anti-infectious treatment or hospitalization Rejections are defined as acute type 2R or 3R cell rejections according to the ISHLT classification | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TTV viral load | Monthly mean of TTV viral concentration load measured by quantitative PCR within 3 months | 3 months | 
| TTV viral load | Monthly mean of TTV viral concentration measured by quantitative PCR within 12 months | 12 months | 
| Infections | Time to viral infections , bacterial and parasitic infections requiring the establishment of anti-infectious treatment or hospitalization during the 12 months post-transplant. | 12 months | 
| Rejections | Time to rejections within the 12 months post-transplant defined as acute type 2R or 3R cell rejections according to the ISHLT classification. | 12 months | 
| Immunosuppressant level | Immunosuppressant pharmacological dosing | 3 months | 
| Immunosuppressant level | Immunosuppressant pharmacological dosing | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TTV, Heart transplant, Viral Load, rejection, infection