Heart TransplantationSAFE-CARENCT07897526
Superiority Assessment of Donor-derived Cell-FreE DNA ( Deoxyribonucleic Acid) for Cardiac Allograft REjection Monitoring
A study testing non-invasive strategy based of the analysis of circulating dd-cfDNA (AlloSeq cfDNA assay) in people with Heart Transplantation, run by Assistance Publique - Hôpitaux de Paris.
Trial summary
Heart transplantation (HTx) remains the gold-standard treatment for patients with end-stage heart failure refractory to the medical management, offering the best survival and quality of life. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Transplantation
- What is being tested?
- non-invasive strategy based of the analysis of circulating dd-cfDNA (AlloSeq cfDNA assay)
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 352 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2026to 1 Nov 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female, age 18 years or older at the time of signing informed consent,
- Heart transplant recipient at 30 to 40 days post-transplant, discharged from the intensive care unit,
- With at least one endomyocardial biopsy showing no signs of significant ongoing allograft rejection (ACR "Acute Cellular Rejection" ≥ 2R and/or pAMR "pathologic Antibody-Mediated Rejection" ≥ pAMR2 according to ISHLT "International Society for Heart and Lung Transplantation" working formulations),
- Able to read, understand and provide written informed consent,
- Able to understand and read French
- Able and willing to comply with the study visit schedule, study procedures and study requirements,
- Affiliation to a social security regime
Who cannot join
- Heart transplantation has been performed for more than 40 days.
- Concurrent multiple solid organ or tissue transplant
- Prior history of any solid organ or cellular transplantation (other than the current heart transplantation).
- Planned use of other commercially available or investigational dd-cfDNA or gene expression profile assays.
- Pregnancy and/or breastfeeding.
- Hemodynamically unstable or other serious medical condition that may adversely affect the subject's ability to participate in the study.
Show all 10Show fewer
- Patient non discharged from ICU within 40 days post-transplant
- Significant allograft rejection (ACR ≥ 2R and/or pAMR ≥ pAMR2) between transplantation and inclusion / randomization.
- Under legal protection measure (tutorship or curatorship) and patient deprived of freedom
- Participation in another interventional clinical trial
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Superiority Assessment of Donor-derived Cell-FreE DNA(Deoxyribonucleic Acid) for Cardiac Allograft REjection Monitoring - A Randomized Clinical Trial
Heart transplantation (HTx) remains the gold-standard treatment for patients with end-stage heart failure refractory to the medical management, offering the best survival and quality of life.
In the absence of a reliable non-invasive biomarker, international guidelines recommend to screen for cardiac allograft rejection during the first-year post-transplant using iterative protocol endomyocardial biopsies, a stressful and invasive procedure at risk of periprocedural complications. This invasive strategy suffers from multiple limitations and is increasingly being questioned.
Read more
Recently, circulating donor-derived cell-free DNA (dd-cfDNA) ""Donor-derived cell-FreE Deoxyribonucleic Acid"", has been proposed as a reliable non-invasive biomarker of rejection in solid organ transplantation. Strong associations between allograft rejection and dd-cfDNA have been found in observational studies.
Although donor-derived cell-free DNA (dd-cfDNA) is considered as the most promising non-invasive biomarker of allograft injury by international experts, no interventional trial has ever confirmed the efficiency and the safety of the non-invasive monitoring of rejection using dd-cfDNA. This prospective validation is mandatory and represents an important unmet medical need.We hypothesize that a non-invasive dd-cfDNA-based strategy might be superior to an invasive biopsy-based strategy for the screening of rejection in terms of patients' survival, allograft function and quality of life.
Read the detailed description
The study aims to demonstrate the superiority of a non-invasive strategy based of the analysis of circulating dd-cfDNA (AlloSeq cfDNA assay) to monitor cardiac allograft rejection during the first-year post-transplant compared to the currently recommended invasive biopsy-based strategy.
The primary endpoint will be a hierarchical composite endpoint evaluated at 11-month post-randomization (win-ratio analysis):
- all-cause mortality or listing for redo heart transplantation;
- acute allograft dysfunction due to biopsy-proven rejection or other causes (see definition in the detailed protocol);
- biopsy-related complications (see definition in the detailed protocol);
- symptoms of anxiety and depression as assessed by the Hospital Anxiety and Depression scale.
The secondary objectives of the study will be:
Safety objectives: analysis of mortality, redo transplantation and usual clinical, histopathologic and echocardiographic parameters of graft function, but also an in-depth allograft evaluation (tissular molecular biology).
Efficiency objectives: The number of biopsies performed in each group will evaluate the potential gain of the non-invasive strategy. This analysis will be completed by a medico-economic analysis to precise the impact of this strategy in the French transplant care environment.
Quality of life of transplant recipients will be assessed using generic and specific scales.
- Conditions
- Heart Transplantation
- Being tested
- non-invasive strategy based of the analysis of circulating dd-cfDNA (AlloSeq cfDNA assay), control
- Keywords
- Cardiac allograft rejection, Donor-derived cell-free DNA,, dd-cfDNA, Heart transplantation, Endomyocardial biopsy, non-invasive strategy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
non-invasive strategy based of the analysis of circulating dd-cfDNA (AlloSeq cfDNA assay)Device
"202 single nucleotide polymorphisms and advanced bioinformatics tools to quantify dd-cfDNA. The quantification of dd-cfDNA will be performed at each follow-up visit (n = 8).
In the experimental group, no protocol EMB will be performed outside of the end-of-study visit (protocol biopsy at Month 11 in both groups). EMB will only be allowed if clinically indicated or in case of abnormal value of dd-cfDNA. "
controlProcedure or surgery
Standard of care monitoring of cardiac allograft rejection based on iterative protocol endomyocardial biopsies during the first-year post-transplant (8 follow-up visits)
| Study group | Role | What they receive |
|---|---|---|
| Quantification of dd-cfDNA "Donor-derived cell-FreE Deoxyribonucleic Acid" | Experimental | Quantification of dd-cfDNA on blood samples without knowing donor and recipient genotyping Receives: Device: non-invasive strategy based of the analysis of circulating dd-cfDNA (AlloSeq cfDNA assay) |
| control | Other | Endomyocardial biopsies during the first-year post-transplant (8 follow-up visits) Receives: Procedure: control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of all-cause mortality or listing for redo heart transplantation
The incidence of all-cause mortality or listing for redo heart transplantation will be assessed from randomization through 11 months after randomization (12 months post-transplant). This is the first component of the hierarchical composite endpoint and will be assessed using clinical follow-up and medical records.
Measured: 11 months after randomization
Incidence (%) of acute allograft dysfunction defined by an absolute decrease in left ventricular ejection fraction (LVEF) of ≥20 percentage points, assessed by transthoracic echocardiography
The incidence of acute cardiac allograft dysfunction defined by an absolute decrease in left ventricular ejection fraction (LVEF) of ≥20 percentage points compared with the reference LVEF measured at the inclusion visit will be assessed from randomization through 11 months after randomization. LVEF will be measured by transthoracic echocardiography performed as part of routine clinical care.
Measured: 11 months after randomization
Incidence (%) of acute allograft dysfunction defined by a several events
Incidence (%) of acute allograft dysfunction defined by a several events : an absolute decrease in left ventricular ejection fraction (LVEF) of ≥20 percentage points, assessed by transthoracic echocardiography OR a proportional decrease in left ventricular ejection fraction (LVEF) of ≥25%, assessed by transthoracic echocardiography, OR by the occurence of hospitalization for acutely decompensated heart failure, assessed by clinical follow-up and medical records.
The incidence of acute cardiac allograft dysfunction defined by a proportional decrease in left ventricular ejection fraction (LVEF) of ≥25% compared with the reference LVEF measured at the inclusion visit will be assessed from randomization through 11 months after randomization. LVEF will be measured by transthoracic echocardiography performed as part of routine clinical care.
Measured: 11 months after randomization
Incidence (%) of post-procedural pericardial effusion requiring surgery, hospitalization, or an additional outpatient monitoring visit, assessed by transthoracic echocardiography
The incidence of new post-procedural pericardial effusion requiring surgery, hospitalization, or an additional outpatient visit for monitoring will be assessed from randomization through 11 months after randomization. Pericardial effusion will be assessed by transthoracic echocardiography performed as part of routine clinical care and compared with the baseline echocardiographic assessment at the inclusion visit.
Measured: 11 months after randomization
Incidence (%) of local venous puncture-site complications requiring surgery, emergency imaging, or hospitalization, assessed by clinical follow-up and medical records
The incidence of local complications at the venous puncture site requiring surgery, emergency imaging, or hospitalization will be assessed from randomization through 11 months after randomization, based on clinical follow-up and review of medical records.
Measured: 11 months after randomization
Mean change from baseline in total Hospital Anxiety and Depression Scale (HADS) score
Symptoms of anxiety and depression will be assessed 11 months after randomization using the Hospital Anxiety and Depression Scale (HADS), a self-administered questionnaire. The outcome will be the change in total HADS score from baseline (inclusion visit) to 11 months after randomization. The total HADS score is calculated by summing the anxiety (HADS-A) and depression (HADS-D) subscale scores and ranges from 0 to 42 points.
Measured: 11 months after randomization
Occurrence of Cardiac allograft vasculopathy
Occurrence Cardiac allograft vasculopathy as assessed either by a coronary angiogram or by a coronary CT-scan (Computed Tomography scan) according to the local protocol (cardiac allograft vasculopathy ≥ grade 2 according to the ISHLT classification (International Society for Heart and Lung Transplantation) (grades range from 0 = no CAV to 3 = severe CAV)
Measured: 11 months after randomization
Occurrence of Diagnosis of rejection
Diagnosis of rejection according to international working formulations (EMB: Endomyocardial Biopsy) performed as part of routine clinical care, acute cellular rejection (ACR) ≥ 2R (ISHLT ACR score range: 0R (no cellular rejection) to 3R (severe cellular rejection)) and/or antibody-mediated rejection (AMR) ≥ pAMR1 (pAMR score range: pAMR0 = no evidence of antibody-mediated rejection to pAMR3 = severe antibody-mediated rejection), according to the ISHLT (International Society for Heart and Lung Transplantation) working formulations
Measured: 11 months after randomization
Occurrence of Molecular cellular rejection
Molecular cellular rejection score on protocol EMB (targeted molecular profiling using NanoString nCounter technology and Banff Human Organ Transplant Panel, a consensual targeted panel comprising 770 genes)
Measured: 11 months after randomization
Secondary outcomes (12)
Occurrence of Molecular antibody-mediated rejection
Molecular antibody-mediated rejection score on protocol EMB (targeted molecular profiling using NanoString nCounter technology and Banff Human Organ Transplant Panel, a consensual targeted panel comprising 770 genes)
Measured: 11 months after randomization
Area under the curve of the targeted calcineurins inhibitors doses (residual concentration)
Exposure to immunosuppressive drugs as assessed by the area under the curve of the percentage of the targeted calcineurins inhibitors doses (percentage of cyclosporine or tacrolimus trough level compared to the reference targets according to international guidelines)
Measured: 1, 2, 5, 8 and 11 month after randomization
Rate of infectious complications
Rate of infectious complications as defined by any symptomatic documented bacterial, viral, fungal, or parasitic infection requiring a specific treatment and/or a minimization of immunosuppression.
Measured: 11 months after randomization
Number of endomyocardial biopsies
Number of endomyocardial biopsies performed during 11 months post randomization,
Measured: 11 months after randomization
incremental cost effectiveness ratio (ICER)
The incremental cost-effectiveness ratio (ICER) will be calculated as the difference in mean costs between the experimental and control groups divided by the difference in effectiveness, with effectiveness measured using the prespecified primary endpoint. The ICER will be expressed as cost per unit of effectiveness gained
Measured: 11 months after randomization
Incremental cost-utility ratio (ICUR)
The incremental cost-utility ratio (ICUR) will be calculated as the difference in mean costs between the experimental and control groups divided by the difference in quality-adjusted life years (QALYs) gained. The ICUR will be expressed as cost per QALY gained.
Measured: 11 months after randomization
Budget impact of the non-invasive dd-cfDNA-based strategy compared with control strategy from the French healthcare system
Budget impact analysis (BIA) conducted according to ISPOR good practice guidelines and French HAS methodological recommendations. The incremental budget impact will be estimated by comparing two scenarios: a world in which the non invasive dd-cfDNA-based strategy is implemented and a counterfactual world without this strategy based on the eligible population in France and assumptions on market uptake. Data on resource use, costs and cost offsets will be derived from the SAFE-CARE trial, supplemented with estimates published in the relevant literature. Results will be expressed in euros (€) as the annual and cumulative incremental budget impact.
Measured: 11 months after randomization
Mean of total Hospital Anxiety and Depression Scale (HADS) score
Anxiety and depression symptoms will be assessed using the total score of the Hospital Anxiety and Depression Scale (HADS), a self-administered questionnaire. The total HADS score ranges from 0 to 42 points, with higher scores indicating greater symptoms of anxiety and depression. The mean total HADS score will be reported at 2, 5, 8, and 11 months after randomization.
Measured: 2, 5, 8 and 11 months after randomization
Mean score of Anxiety and Depression
Anxiety and Depression score assessed by HAD (Hospital Anxiety and Depression scale) questionnaire (Scores range from 0 to 21 for each subscale, with higher scores "21" = more severe anxiety or depression; 0 = no symptoms): mean scores and proportion of patients with definite symptomatology of anxiety and depression (overall score ≥ 11 points)
Measured: 2, 5, 8 and 11 months after randomization
Proportion of patients with clinically relevant anxiety and depression symptoms
The proportion of patients with clinically relevant symptoms of anxiety and depression will be assessed using the total Hospital Anxiety and Depression Scale (HADS) score. Clinically relevant symptomatology will be defined as a total HADS score ≥11 points.
Measured: 2, 5, 8 and 11 months after randomization
Mean score of EQ-5D-5L health status
Health-related quality of life will be assessed using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire. The EQ-5D-5L assesses five dimensions of health, each rated from 1 (no problems) to 5 (extreme problems). The health status profile will be reported at 2, 5, 8, and 11 months after randomization.
Measured: 2, 5, 8 and 11 months after randomization
Mean of Visual Analog Scale (EQ VAS) score
Health-related quality of life will be assessed using the EuroQol Visual Analog Scale (EQ VAS). The EQ VAS score ranges from 0 to 100 points, with 0 representing the worst imaginable health state and 100 representing the best imaginable health state. The EQ VAS score will be reported at 2, 5, 8, and 11 months after randomization..
Measured: 2, 5, 8 and 11 months after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2026
- Study start1 Dec 2026 (estimated)
- Primary completion1 Nov 2030 (estimated)
- Study completion1 Nov 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart TransplantationStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 352 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Guillaume COUTANCE, MD,PHD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07897526
- Sponsor's protocol ID
- APHP251599
- Other IDs
- IDRCB n°: 2025-A02963-46
- Acronym
- SAFE-CARE
- Status last verified
- Sep 2026
- First submitted
- 28 Sep 2026
- Last updated
- 27 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Plan to Share IPD: Due to the procedures approved by the French data privacy authority (Commission nationale de l'informatique et des libertés - CNIL), and the content of the informed consent forms signed by participants, full database transmission is not authorized. However, consultation of deidentified individual participant data may be considered for editorial boards or qualified researchers, upon reasonable request and under strict regulatory safeguards, subject to prior agreement on terms and conditions of access.
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Superiority Assessment of Donor-derived Cell-FreE DNA(Deoxyribonucleic Acid) for Cardiac Allograft REjection Monitoring - A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT07897526
- Acronym / sponsor ID
- SAFE-CARE / APHP251599
- Conditions
- Heart Transplantation
- Keywords
- Cardiac allograft rejection, Donor-derived cell-free DNA,, dd-cfDNA, Heart transplantation, Endomyocardial biopsy, non-invasive strategy
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 352 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 1 Dec 2026 (estimated)
- Primary completion
- 1 Nov 2030 (estimated)
- Study completion
- 1 Nov 2030 (estimated)
- First posted
- 27 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Heart transplantation (HTx) remains the gold-standard treatment for patients with end-stage heart failure refractory to the medical management, offering the best survival and quality of life.
In the absence of a reliable non-invasive biomarker, international guidelines recommend to screen for cardiac allograft rejection during the first-year post-transplant using iterative protocol endomyocardial biopsies, a stressful and invasive procedure at risk of periprocedural complications. This invasive strategy suffers from multiple limitations and is increasingly being questioned.
Recently, circulating donor-derived cell-free DNA (dd-cfDNA) ""Donor-derived cell-FreE Deoxyribonucleic Acid"", has been proposed as a reliable non-invasive biomarker of rejection in solid organ transplantation. Strong associations between allograft rejection and dd-cfDNA have been found in observational studies.
Although donor-derived cell-free DNA (dd-cfDNA) is considered as the most promising non-invasive biomarker of allograft injury by international experts, no interventional trial has ever confirmed the efficiency and the safety of the non-invasive monitoring of rejection using dd-cfDNA. This prospective validation is mandatory and represents an important unmet medical need.We hypothesize that a non-invasive dd-cfDNA-based strategy might be superior to an invasive biopsy-based strategy for the screening of rejection in terms of patients' survival, allograft function and quality of life.
Detailed description
The study aims to demonstrate the superiority of a non-invasive strategy based of the analysis of circulating dd-cfDNA (AlloSeq cfDNA assay) to monitor cardiac allograft rejection during the first-year post-transplant compared to the currently recommended invasive biopsy-based strategy.
The primary endpoint will be a hierarchical composite endpoint evaluated at 11-month post-randomization (win-ratio analysis):
- all-cause mortality or listing for redo heart transplantation;
- acute allograft dysfunction due to biopsy-proven rejection or other causes (see definition in the detailed protocol);
- biopsy-related complications (see definition in the detailed protocol);
- symptoms of anxiety and depression as assessed by the Hospital Anxiety and Depression scale.
The secondary objectives of the study will be:
Safety objectives: analysis of mortality, redo transplantation and usual clinical, histopathologic and echocardiographic parameters of graft function, but also an in-depth allograft evaluation (tissular molecular biology).
Efficiency objectives: The number of biopsies performed in each group will evaluate the potential gain of the non-invasive strategy. This analysis will be completed by a medico-economic analysis to precise the impact of this strategy in the French transplant care environment.
Quality of life of transplant recipients will be assessed using generic and specific scales.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Quantification of dd-cfDNA "Donor-derived cell-FreE Deoxyribonucleic Acid" | Experimental | Device: non-invasive strategy based of the analysis of circulating dd-cfDNA (AlloSeq cfDNA assay)Quantification of dd-cfDNA on blood samples without knowing donor and recipient genotyping |
| control | Other | Procedure: controlEndomyocardial biopsies during the first-year post-transplant (8 follow-up visits) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female, age 18 years or older at the time of signing informed consent,
- Heart transplant recipient at 30 to 40 days post-transplant, discharged from the intensive care unit,
- With at least one endomyocardial biopsy showing no signs of significant ongoing allograft rejection (ACR "Acute Cellular Rejection" ≥ 2R and/or pAMR "pathologic Antibody-Mediated Rejection" ≥ pAMR2 according to ISHLT "International Society for Heart and Lung Transplantation" working formulations),
- Able to read, understand and provide written informed consent,
- Able to understand and read French
Key exclusion criteria (10 listed)
- Heart transplantation has been performed for more than 40 days.
- Concurrent multiple solid organ or tissue transplant
- Prior history of any solid organ or cellular transplantation (other than the current heart transplantation).
- Planned use of other commercially available or investigational dd-cfDNA or gene expression profile assays.
- Pregnancy and/or breastfeeding.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| non-invasive strategy based of the analysis of circulating dd-cfDNA (AlloSeq cfDNA assay)"202 single nucleotide polymorphisms and advanced bioinformatics tools to quantify dd-cfDNA. The quantification of dd-cfDNA will be performed at each follow-up visit (n = 8). In the experimental group, no protocol EMB will be performed outside of the end-of-study visit (protocol biopsy at Month 11 in both groups). EMB will only be allowed if clinically indicated or in case of abnormal value of dd-cfDNA. " | Device | Quantification of dd-cfDNA "Donor-derived cell-FreE Deoxyribonucleic Acid" |
| controlStandard of care monitoring of cardiac allograft rejection based on iterative protocol endomyocardial biopsies during the first-year post-transplant (8 follow-up visits) | Procedure or surgery | control |
Primary outcome
Incidence of all-cause mortality or listing for redo heart transplantation
Time frame: 11 months after randomization
The incidence of all-cause mortality or listing for redo heart transplantation will be assessed from randomization through 11 months after randomization (12 months post-transplant). This is the first component of the hierarchical composite endpoint and will be assessed using clinical follow-up and medical records.
Incidence (%) of acute allograft dysfunction defined by an absolute decrease in left ventricular ejection fraction (LVEF) of ≥20 percentage points, assessed by transthoracic echocardiography
Time frame: 11 months after randomization
The incidence of acute cardiac allograft dysfunction defined by an absolute decrease in left ventricular ejection fraction (LVEF) of ≥20 percentage points compared with the reference LVEF measured at the inclusion visit will be assessed from randomization through 11 months after randomization. LVEF will be measured by transthoracic echocardiography performed as part of routine clinical care.
Incidence (%) of acute allograft dysfunction defined by a several events
Time frame: 11 months after randomization
Incidence (%) of acute allograft dysfunction defined by a several events : an absolute decrease in left ventricular ejection fraction (LVEF) of ≥20 percentage points, assessed by transthoracic echocardiography OR a proportional decrease in left ventricular ejection fraction (LVEF) of ≥25%, assessed by transthoracic echocardiography, OR by the occurence of hospitalization for acutely decompensated heart failure, assessed by clinical follow-up and medical records. The incidence of acute cardiac allograft dysfunction defined by a proportional decrease in left ventricular ejection fraction (LVEF) of ≥25% compared with the reference LVEF measured at the inclusion visit will be assessed from randomization through 11 months after randomization. LVEF will be measured by transthoracic echocardiography performed as part of routine clinical care.
Incidence (%) of post-procedural pericardial effusion requiring surgery, hospitalization, or an additional outpatient monitoring visit, assessed by transthoracic echocardiography
Time frame: 11 months after randomization
The incidence of new post-procedural pericardial effusion requiring surgery, hospitalization, or an additional outpatient visit for monitoring will be assessed from randomization through 11 months after randomization. Pericardial effusion will be assessed by transthoracic echocardiography performed as part of routine clinical care and compared with the baseline echocardiographic assessment at the inclusion visit.
Incidence (%) of local venous puncture-site complications requiring surgery, emergency imaging, or hospitalization, assessed by clinical follow-up and medical records
Time frame: 11 months after randomization
The incidence of local complications at the venous puncture site requiring surgery, emergency imaging, or hospitalization will be assessed from randomization through 11 months after randomization, based on clinical follow-up and review of medical records.
Mean change from baseline in total Hospital Anxiety and Depression Scale (HADS) score
Time frame: 11 months after randomization
Symptoms of anxiety and depression will be assessed 11 months after randomization using the Hospital Anxiety and Depression Scale (HADS), a self-administered questionnaire. The outcome will be the change in total HADS score from baseline (inclusion visit) to 11 months after randomization. The total HADS score is calculated by summing the anxiety (HADS-A) and depression (HADS-D) subscale scores and ranges from 0 to 42 points.
Occurrence of Cardiac allograft vasculopathy
Time frame: 11 months after randomization
Occurrence Cardiac allograft vasculopathy as assessed either by a coronary angiogram or by a coronary CT-scan (Computed Tomography scan) according to the local protocol (cardiac allograft vasculopathy ≥ grade 2 according to the ISHLT classification (International Society for Heart and Lung Transplantation) (grades range from 0 = no CAV to 3 = severe CAV)
Occurrence of Diagnosis of rejection
Time frame: 11 months after randomization
Diagnosis of rejection according to international working formulations (EMB: Endomyocardial Biopsy) performed as part of routine clinical care, acute cellular rejection (ACR) ≥ 2R (ISHLT ACR score range: 0R (no cellular rejection) to 3R (severe cellular rejection)) and/or antibody-mediated rejection (AMR) ≥ pAMR1 (pAMR score range: pAMR0 = no evidence of antibody-mediated rejection to pAMR3 = severe antibody-mediated rejection), according to the ISHLT (International Society for Heart and Lung Transplantation) working formulations
Occurrence of Molecular cellular rejection
Time frame: 11 months after randomization
Molecular cellular rejection score on protocol EMB (targeted molecular profiling using NanoString nCounter technology and Banff Human Organ Transplant Panel, a consensual targeted panel comprising 770 genes)
12 secondary outcomes
Occurrence of Molecular antibody-mediated rejection
Time frame: 11 months after randomization
Area under the curve of the targeted calcineurins inhibitors doses (residual concentration)
Time frame: 1, 2, 5, 8 and 11 month after randomization
Rate of infectious complications
Time frame: 11 months after randomization
Number of endomyocardial biopsies
Time frame: 11 months after randomization
incremental cost effectiveness ratio (ICER)
Time frame: 11 months after randomization
Incremental cost-utility ratio (ICUR)
Time frame: 11 months after randomization
Budget impact of the non-invasive dd-cfDNA-based strategy compared with control strategy from the French healthcare system
Time frame: 11 months after randomization
Mean of total Hospital Anxiety and Depression Scale (HADS) score
Time frame: 2, 5, 8 and 11 months after randomization
Mean score of Anxiety and Depression
Time frame: 2, 5, 8 and 11 months after randomization
Proportion of patients with clinically relevant anxiety and depression symptoms
Time frame: 2, 5, 8 and 11 months after randomization
Mean score of EQ-5D-5L health status
Time frame: 2, 5, 8 and 11 months after randomization
Mean of Visual Analog Scale (EQ VAS) score
Time frame: 2, 5, 8 and 11 months after randomization
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2026.
- Individual participant dataSharing planned: Yes. Plan to Share IPD: Due to the procedures approved by the French data privacy authority (Commission nationale de l'informatique et des libertés - CNIL), and the content of the informed consent forms signed by participants, full database transmission is not authorized. However, consultation of deidentified individual participant data may be considered for editorial boards or qualified researchers, upon reasonable request and under strict regulatory safeguards, subject to prior agreement on terms and conditions of access.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Guillaume COUTANCE, MD,PHD principal investigator
Assistance Publique - Hôpitaux de Paris
Questions about this trial
What is this clinical trial studying?
A study testing non-invasive strategy based of the analysis of circulating dd-cfDNA (AlloSeq cfDNA assay) in people with Heart Transplantation, run by Assistance Publique - Hôpitaux de Paris.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Guillaume COUTANCE, MD, PHD (+331 56 09 29 64, guillaume.coutance@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of all-cause mortality or listing for redo heart transplantation (time frame: 11 months after randomization). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2026.