HeartCare Immuno-optimization in Cardiac Allografts (MOSAIC)

NCT05459181 | Not Yet Recruiting DMC FDA Device

• 1 other identifier: SN-C-00021
• Study Type: interventional
• Target: 930
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an unblinded, randomized, controlled, two-arm interventional research study enrolling patients who are undergoing heart transplantation. The aim of the study is to determine whether patients at low risk of rejection can safely reduce the doses of their post-transplant immunosuppression medications using a combination of tests that include donor-specific antibodies (DSA), histology (looking at tissue from the donor heart), donor-derived cell-free DNA (AlloSure), and gene expression profiling (AlloMap). Eligible participants will be randomized in a 1:1 ratio into the HeartCare immune-optimization (intervention) arm or the corresponding observational (control) arm. AlloSure and AlloMap are the components of the HeartCare panel developed by CareDx.

Conditions

Heart Transplant; Immunosuppression; Allograft

Keywords

HeartCare; Allograft loss and survival; Calcineurin inhibitors; Chronic immunosuppression; Steroid avoidance; Donor-specific antibodies; Donor-derived cell-free DNA; AlloSure; AlloMap; Gene expression profiling

Outcome Measures

Primary Outcomes (13)

• Incidence of Allograft loss at 12-months post-transplant (safety)

  Demonstrate the safety and efficacy of HeartCare as a tool to successfully optimize immunosuppressant agents using regular surveillance for safe drug minimization.

  12 months

• Incidence of Allograft loss at 24-months post-transplant (safety)

  Demonstrate the safety and efficacy of HeartCare as a tool to successfully optimize immunosuppressant agents using regular surveillance for safe drug minimization.

  24 months

• Total number of acute rejection episodes (ACR >2R or AMR*) at 12-months post-transplant (safety)

  Demonstrate the safety and efficacy of HeartCare as a tool to successfully optimize immunosuppressant agents using regular surveillance for safe drug minimization.

  12 months

• Total number of acute rejection episodes (ACR >2R or AMR*) at 24-months post-transplant (safety)

  Demonstrate the safety and efficacy of HeartCare as a tool to successfully optimize immunosuppressant agents using regular surveillance for safe drug minimization.

  24 months

• EQ-5D survey performed at 12-months post-transplant to assess allograft function (safety)

  Demonstrate the safety and efficacy of HeartCare as a tool to successfully optimize immunosuppressant agents using regular surveillance for safe drug minimization.

  12 months

• TTE imaging performed at 12-months post-transplant to assess allograft function (safety)

  Demonstrate the safety and efficacy of HeartCare as a tool to successfully optimize immunosuppressant agents using regular surveillance for safe drug minimization.

  12 months

• EQ-5D survey performed at 24-months post-transplant to assess allograft function (safety)

  Demonstrate the safety and efficacy of HeartCare as a tool to successfully optimize immunosuppressant agents using regular surveillance for safe drug minimization.

  24 months

• TTE imaging performed at 24-months post-transplant to assess allograft function (safety)

  Demonstrate the safety and efficacy of HeartCare as a tool to successfully optimize immunosuppressant agents using regular surveillance for safe drug minimization.

  24 months

• Incidence of dnDSA formation at 12-months post-transplant (safety and efficacy)

  Demonstrate the safety and efficacy of HeartCare as a tool to successfully optimize immunosuppressant agents using regular surveillance for safe drug minimization.

  12 months

• Incidence of dnDSA formation at 24-months post-transplant (safety and efficacy)

  Demonstrate the safety and efficacy of HeartCare as a tool to successfully optimize immunosuppressant agents using regular surveillance for safe drug minimization.

  24 months

• Change in eGFR at 12-months post-transplant (efficacy)

  Demonstrate the safety and efficacy of HeartCare as a tool to successfully optimize immunosuppressant agents using regular surveillance for safe drug minimization.

  12 months

• Change in eGFR at 24-months post-transplant (efficacy)

  Demonstrate the safety and efficacy of HeartCare as a tool to successfully optimize immunosuppressant agents using regular surveillance for safe drug minimization.

  24 months

• Total number of biopsies performed post-transplant, including both surveillance and clinically indicated biopsies (efficacy)

  Demonstrate the safety and efficacy of HeartCare as a tool to successfully optimize immunosuppressant agents using regular surveillance for safe drug minimization.

  24 months

Secondary Outcomes (3)

• Histological assessment of tissue biopsy with paired AlloSure dd-cfDNA and AlloMap GEP results (HeartCare) - performed both 'For Cause' and 'Surveillance' using standard biopsy assessment.

  6 months

• Association between AlloSure dd-cfDNA and AlloMap GEP (HeartCare) results with successful immuno-optimization, longitudinal clinical/laboratory parameters (dnDSA), and histologic data (allograft rejection, CAV).

  24 months

• Data collection from patient medical record, to capture episodes of infection, viral PCR results, changes in immunosuppression and treatment of rejection, as well as all adverse advents.

  24 months

Study Arms (2)

Control arm

NO INTERVENTION

465 participants undergoing standard of care post-transplant surveillance

Intervention arm

EXPERIMENTAL

465 participants undergoing HeartCare protocol surveillance

Diagnostic Test: HeartCare

Interventions

HeartCare DIAGNOSTIC_TEST

Using HeartCare platform as a tool to successfully augment immunosuppressant agents through regular surveillance allowing minimization of doses and number of agents.

Intervention arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Heart transplant recipients \<2 weeks post-transplant
• Patients aged 18 years or older
• Planned post-transplant maintenance immunosuppression regimen consisting of prednisolone, tacrolimus and mycophenolate
• Female participants of childbearing potential must be willing to ensure that they or their partner use effective contraception during the trial and for 3 months thereafter
• Participant is willing and able to give informed consent for participation in the trial
• In the Investigator's opinion, is able and willing to comply with all trial requirements

You may not qualify if:

• The participant may not enter the trial if ANY of the following apply:
• Multi-visceral transplant recipients
• Female participant who is pregnant, lactating or planning pregnancy during the trial
• Heart transplant recipients undergoing desensitization protocols prior to transplant based off high immunological risk profiles (determined by treating clinician)
• Chronic oral steroid use for any reason that cannot be tapered off and discontinued
• Planned post-transplant immunosuppression regimen utilizing cyclosporine, azathioprine, mTOR inhibitors, and/or co-stimulatory blockers
• Contraindication to having AlloSure or AlloMap testing
• Participant with life expectancy of less than 6 months or is inappropriate for immuno-optimization (including those patients at increased risk of primary disease recurrence w/ reduction in post-transplant immunosuppression)
• Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial. This includes clinical events that would significantly impact post-transplant immunosuppression such as major infectious complications or significant rejection episodes within the first month post-transplant.
• Participants who are currently or have previously participated in another research trial involving an investigational immunological drug in the past 12 weeks
• Any condition that would preclude protocol biopsies
• Randomization Criteria (assessed at Week 4)
• The participant may not proceed with randomization if ANY of the following apply at Week 4 post-transplant:
• Maintenance immunosuppression that includes cyclosporine, azathioprine, mTOR inhibitors, and/or co-stimulatory blockers
• Any episodes of biopsy-proven acute rejection (ACR ≥2R or AMR\*)

Sponsors & Collaborators

• CareDx: lead

Central Study Contacts

Anna Thomas

CONTACT

415-780-2752; athomas@caredx.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2022
• First Posted: July 14, 2022
• Study Start: December 1, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: October 23, 2024

Record last verified: 2024-10