HeartCare Immuno-optimization in Cardiac Allografts (MOSAIC) (MOSAIC)

October 21, 2024 updated by: CareDx

Molecular Outcome Surveillance Using AlloSure and AlloMap Guided Immunomodulation in Cardiac Transplant

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is an open-label randomized controlled two-arm interventional trial. Eligible patients starting triple maintenance therapy (tacrolimus, mycophenolate mofetil and prednisone) post-transplant will be randomized at a 1:1 ratio into the HeartCare immuno-optimization (intervention) arm or the corresponding observational (control) arm. Participants enrolled in the study will begin HeartCare testing as specified in the protocol. All centers will use their own induction regimen provided that the induction practice represents standard of care. Participants will be randomized at 4-weeks post-transplant, assuming they meet requisite clinical/laboratory/histological criteria to proceed. In the Interventional Arm, participants will begin stepwise optimization of their immunosuppression regimen based on their HeartCare, clinical DSA testing, and histology. Patient data (including diagnosis and biopsy outcomes) will be collected through an electronic data capture portal where key results will be transcribed from the hospital EMR into the portal.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
930

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Heart transplant recipients <2 weeks post-transplant
  2. Patients aged 18 years or older
  3. Planned post-transplant maintenance immunosuppression regimen consisting of prednisolone, tacrolimus and mycophenolate
  4. 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
  5. Participant is willing and able to give informed consent for participation in the trial
  6. In the Investigator's opinion, is able and willing to comply with all trial requirements

Exclusion Criteria:

The participant may not enter the trial if ANY of the following apply:

  1. Multi-visceral transplant recipients
  2. Female participant who is pregnant, lactating or planning pregnancy during the trial
  3. Heart transplant recipients undergoing desensitization protocols prior to transplant based off high immunological risk profiles (determined by treating clinician)
  4. Chronic oral steroid use for any reason that cannot be tapered off and discontinued
  5. Planned post-transplant immunosuppression regimen utilizing cyclosporine, azathioprine, mTOR inhibitors, and/or co-stimulatory blockers
  6. Contraindication to having AlloSure or AlloMap testing
  7. 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)
  8. 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.
  9. Participants who are currently or have previously participated in another research trial involving an investigational immunological drug in the past 12 weeks
  10. 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:

  1. Maintenance immunosuppression that includes cyclosporine, azathioprine, mTOR inhibitors, and/or co-stimulatory blockers
  2. Any episodes of biopsy-proven acute rejection (ACR ≥2R or AMR*)
  3. Abnormal molecular profile defined as AlloSure >0.2%
  4. Allograft dysfunction defined as LVEF <45%
  5. eGFR <30mL/min
  6. Presence of DSA (persistence of any pre-transplant DSA or dnDSA) *AMR 1 (H+) with DSA/graft dysfunction or AMR > 2

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
No Intervention: Control arm
465 participants undergoing standard of care post-transplant surveillance
Experimental: Intervention arm
465 participants undergoing HeartCare protocol surveillance
Diagnostic test: HeartCare
Using HeartCare platform as a tool to successfully augment immunosuppressant agents through regular surveillance allowing minimization of doses and number of agents.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Incidence of Allograft loss at 12-months post-transplant (safety)
Time Frame: 12 months
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)
Time Frame: 24 months
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)
Time Frame: 12 months
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)
Time Frame: 24 months
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)
Time Frame: 12 months
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)
Time Frame: 12 months
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)
Time Frame: 24 months
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)
Time Frame: 24 months
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)
Time Frame: 12 months
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)
Time Frame: 24 months
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)
Time Frame: 12 months
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)
Time Frame: 24 months
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)
Time Frame: 24 months
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 6 months
Identify correlation between HeartCare and histopathological allograft rejection based on all clinical biopsies.
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).
Time Frame: 24 months
Establish temporal relationships between HeartCare and allograft injury patterns such as dnDSA formation, allograft rejection and 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.
Time Frame: 24 months
Assessment of all medical events throughout the duration of the study.
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
CareDx

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 22, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 12, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 14, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 23, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 21, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2024

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SN-C-00021

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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