Diagnostic and Therapeutic Applications of Microarrays in Heart Transplantation

Recruiting

• Conditions: Cardiac Transplant Disorder

• Registration Number: NCT02670408
• Lead Sponsor: University of Alberta

Brief Summary

Demonstrate the impact of the Molecular Microscope Diagnostic System as the standard of care for heart transplant patients.

Detailed Description

The current standard for biopsy-based diagnoses of rejection of heart transplants is the ISHLT classification from 2004, which represents a widely-used international consensus, based on morphological criteria of the cellular infiltrate within the myocardial specimen system with certainties and some arbitrary and blurred parameters. Recent data-driven approaches using molecular and conventional technologies indicate that this system produces incorrect diagnoses with potential harm to patients due to inappropriate treatment. To address this unmet need and improve diagnostics in the area of organ transplantation, the Alberta Transplant Applied Genomics Centre (ATAGC, University of Alberta) has developed a new diagnostic system - the Molecular Microscope® Diagnostic System (MMDx) that interprets biopsies in terms of their molecular phenotype, and combines the molecular and histopathological features of transplant biopsies, plus clinical and laboratory parameters, to create the first Integrated Diagnostic System. The MMDx developed first in kidney transplant biopsies because phenotypes are well established, will now be adapted to heart transplant endomyocardial biopsies (EMBs). The present study will develop a Reference Set of EMB, adapt the MMDx system to assess and report EMBs; and validate and refine this system in 900 unselected prospectively collected for clinical indications and a standard of care EMBs from North American and European Centers. In addition to demonstrating the real-time feasibility and potential value of this System in patient care, the study will develop and optimize a transparent and user-friendly reporting format to communicate this information to clinicians and obtain detailed feedback to improve its utility. We refine now our MMDx system using a new type of analysis (see primary outcome) and the resulting MMDx report. Currently, INTERHEART recruited 1912 biopsies from 1279 patients.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2016-01
• Study First Submitted: 2016-01-22
• Study First Submitted QC: 2016-01-27
• Study First Posted: 2016-02-01
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-05
• Last Update Posted: 2024-12-06
• Primary Completion: 2025-12
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 900

Inclusion Criteria

• biopsy for clinical indications

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Exclusion Criteria

• no consent
• pregnant women

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Assign molecular scores (probability) of T cell mediated rejection, antibody mediated rejection in heart transplant biopsies, in a reference set of 200 biopsies	2 years	Create a molecular classifier that predicts antibody mediated and T cell mediated rejection, based on the archetypal analysis.

Secondary Outcome Measures

Name	Time	Method
Assign in real time (three working days upon biopsy receipt) molecular scores (probability) of T cell mediated rejection and antibody mediated rejection.	1 year	The molecular phenotype of a newly acquired sample predicts the histologic and clinical features of this sample when compared to the reference set.

Trial Locations

Locations (13)

Cardiac Transplantation Laboratory, The Victor Chang Cardiac Research Institute; 🇦🇺 Darlinghurst, Australia

Department of Cardiac Surgery, Medical University of Vienna; 🇦🇹 Vienna, Austria

UCLA Medical Centre; 🇺🇸 Los Angeles, California, United States

Cedars-Sinai Heart Institute; 🇺🇸 Los Angeles, California, United States

Annette C. and Harold C. Simmons Transplant Institute, BaylorScott&White Research Institute; 🇺🇸 Dallas, Texas, United States

Cardiovascular Medicine, University of Utah Health; 🇺🇸 Salt Lake City, Utah, United States

Virginia Commonwealth University, Division of Cardiology; 🇺🇸 Richmond, Virginia, United States

Heart Failure and Heart Transplant Unit, University of Bologna; 🇮🇹 Bologna, Italy

Advanced Heart Failure Transplant Unit; 🇪🇸 La Coruna, Spain

Alberta Transplant Applied Genomics Center, University of Alberta; 🇨🇦 Edmonton, Alberta, Canada

Division of Cardiology, University of Alberta; 🇨🇦 Edmonton, Alberta, Canada

Institute for Clinical and Experimental Medicine - IKEM; 🇨🇿 Prague, Czechia

Service de Néphrologie-Dialyse Adultes , Hôpital Necker-Enfants Malades; 🇫🇷 Paris, France