TTV Viral Load in Heart Transplant Recipients (TTVCoeur)

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

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.

Study Overview

• Status: Completed
• Conditions: Heart Transplant Infection; Heart Transplant Rejection; Virus
• Intervention / Treatment: Other: Collection of EDTA blood sample (5 to 7 ml)

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Hôpital Européen Georges Pompidou
  • Rennes, France, 35033
    • CHU de Rennes
  • Strasbourg, France, 67091
    • CHU Strasbourg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with first heart transplant

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

All the patients included in the study; 50 patients, at least 18 years old, first heart transplant

Other: Collection of EDTA blood sample (5 to 7 ml); 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: BioMérieux
• Investigators: Principal Investigator: Hélène PERE, Pharm D, PhD, Hôpital Européen Georges-Pompidou; Study Director: David VEYER, Pharm D, PhD, Hôpital Européen Georges-Pompidou

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2022
• Primary Completion (Actual): October 23, 2024
• Study Completion (Actual): October 23, 2024

Study Registration Dates

• First Submitted: September 22, 2021
• First Submitted That Met QC Criteria: September 22, 2021
• First Posted (Actual): October 1, 2021

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: TTV, Heart transplant, Viral Load, rejection, infection
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Osteochondrodysplasias; Bone Diseases, Developmental; Behavior; Social Behavior; Infections; Virus Diseases; Rejection, Psychology; Langer-Giedion Syndrome
• Other Study ID Numbers: APHP201167; 2020-A03456-33 (Other Identifier: IDRCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared
• IPD Sharing Time Frame: Two years after the last publication
• IPD Sharing Access Criteria: Data sharing must be accepted by the sponsor and the PI based on a scientific project and scientific involvement of the PI team. Collaboration will be fostered. Data sharing must respect the agreements made with funders. Teams wishing obtain IPD must meet the sponsor and IP team to present scientific (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasibility and financial support will be discussed before mandatory contractual agreement. Processing of shared data must comply with European General Data Protection Regulation (GDPR).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No