Outcomes AlloMap Registry: the Long-term Management and Outcomes of Heart Transplant Recipients With AlloMap Testing (OAR)

Outcomes AlloMap Registry Study: the Clinical Long-term Management and Outcomes of Heart Transplant Recipients With Regular Rejection Surveillance Including Use of AlloMap Gene-expression Profiling Testing

The objective of this registry is to observe short and long term clinical outcomes in heart transplant recipients who receive regular AlloMap testing as part of allograft rejection surveillance.

Study Overview

• Status: Unknown
• Conditions: Heart Diseases; Cardiac Transplant Rejection; Cardiac Transplant Failure

Detailed Description

The standard of care in adult heart transplant recipients has been to perform periodic endomyocardial biopsies for surveillance for rejection. Because of the risks and discomforts associated with the biopsy procedure, a non-invasive test (AlloMap) based on gene-expression profiling of peripheral blood was developed and introduced in 2005 to identify heart transplant recipients who have a low probability of rejection at the time of protocol surveillance testing. The schedule of AlloMap surveillance testing has been derived from the customary timing of surveillance biopsies: e.g. at 1 to 2 month intervals for patients who are 6 and 12 post-transplantation, and at 3, 4 or 6 months after the first year post-transplantation.

In the large multicenter IMAGE (Invasive Monitoring Attenuation by Gene Expression Profiling) 602 patients in the United States who had undergone cardiac transplantation at least 6 months prior were randomized 1:1 to either surveillance with routine biopsy or AlloMap testing. Patients in both groups were also monitored with echocardiography. A primary outcome event was defined as an episode of rejection with hemodynamic compromise, graft dysfunction due to other causes, death or retransplantation. Over a median follow-up period of 19 months, 297 patients who were monitored with AlloMap and 305 patients who underwent routine biopsies had similar 2-year cumulative rates of events (14.5% and 15.3%, respectively; hazard ratio with gene-expression profiling, 1.04; 95% confidence interval, 0.67 to 1.68).

This Outcomes AlloMap Registry (OAR) study is designed to collect similar clinical outcomes information as studied in IMAGE, in a larger cohort of patients (approximately 2000) followed for up to 5 years. At each routine clinic visit, key clinical features such as rejection surveillance management schedules, testing results (e.g. blood levels of immunosuppressive agents), and AlloMap scores will be collected. This larger and longer term follow-up dataset is intended to enable further elucidation, through analyses techniques such as multivariate Cox proportional hazards models, of the surveillance management features which may be associated or contribute to the most favorable long term outcomes of the heart recipients.

• Study Type: Observational
• Enrollment (Actual): 2444

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
  • California
    • Beverly Hills, California, United States, 90211
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
    • Stanford, California, United States, 94305
      • Stanford University
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida,
    • Hollywood, Florida, United States, 33021
      • Memorial Regional Hospital
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • St. Vincent Medical Group
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Mid America Heart Institute - St. Luke's Hospital
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Integris Baptist Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University
    • Philadelphia, Pennsylvania, United States, 19102
      • Drexel University
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 15219
      • University of Pittsburgh Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Dallas, Texas, United States, 75246
      • Baylor Research Institute
    • Houston, Texas, United States, 77030
      • Houston Methodist Research Institute
    • Houston, Texas, United States, 77030
      • Baylor St. Lukes
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Heart Institute
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Heart & Vascular Institute
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora St. Luke's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Heart transplant patients

Description

Inclusion Criteria:

• New and existing heart transplant recipients ≥ 2 months (≥ 55 days) post-transplant receiving post-transplant care at the enrolling centers for interim surveillance monitoring that includes AlloMap testing

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Heart transplant recipients; Heart transplant rejection surveillance including AlloMap testing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vital status of heart transplant recipient	Hospitalizations and causes (i.e. infections or graft dysfunction (classified as: acute cellular rejection, antibody mediated rejection , cardiac allograft vasculopathy or non specific etiology of graft dysfunction Cancers (newly diagnosed and/or recurrent): onset and classification of types of cancers	5 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surveillance visit schedules and patient management parameters	Endomyocardial biopsy and histology grades of rejection; left ventricular echocardiograms and ejection fractions; maintenance immunosuppressive drugs categories and doses/ blood levels; AlloMap scores and score patterns	5 Years

Collaborators and Investigators

• Sponsor: CareDx
• Investigators: Study Director: James P Yee, MD, PhD, CareDx, Inc., Brisbane, CA

Publications and helpful links

General Publications

• Pham MX, Teuteberg JJ, Kfoury AG, Starling RC, Deng MC, Cappola TP, Kao A, Anderson AS, Cotts WG, Ewald GA, Baran DA, Bogaev RC, Elashoff B, Baron H, Yee J, Valantine HA; IMAGE Study Group. Gene-expression profiling for rejection surveillance after cardiac transplantation. N Engl J Med. 2010 May 20;362(20):1890-900. doi: 10.1056/NEJMoa0912965. Epub 2010 Apr 22.
• Shah MR, Starling RC, Schwartz Longacre L, Mehra MR; Working Group Participants. Heart transplantation research in the next decade--a goal to achieving evidence-based outcomes: National Heart, Lung, And Blood Institute Working Group. J Am Coll Cardiol. 2012 Apr 3;59(14):1263-9. doi: 10.1016/j.jacc.2011.11.050.
• Kanwar, M. et al: Correlation of Longitudinal Gene-Expression Profiling Score to Cytomegalovirus (CMV) Infection: Results from the Outcomes AlloMap Registry (OAR). ISHLT 35th Annual Meeting and Scientific Sessions. 2015 April 13-18, 2015; Nice, France. *2015 American Transplant Congress. May 2-6, 2015; Philadelphia, PA. Poster.
• Teuteberg, J. et al; Gene-Expression Profiling to Monitor for Rejection-Which Patients are Being Offered This Strategy? ISHLT 35th Annual Meeting and Scientific Sessions. 2015 April 13-18, 2015; Nice, France. 2015. *American Transplant Congress. May 2-6, 2015; Philadelphia, PA. Poster.
• Sulemanjee, N. et al; Gender-Mismatched Heart Transplants and Gene Expression Profiling Score-Lessons Learned from the Outcomes AlloMap Registry (OAR). ISHLT 35th Annual Meeting and Scientific Sessions. 2015 April 13-18, 2015; Nice, France. 2015 *American Transplant Congress. May 2-6, 2015; Philadelphia, PA. Poster.
• Kanwar, M. et al; Impact of Cytomegalovirus Infection on Longitudinal Gene-Expression Profiling Score: Results from the Outcomes AlloMap Registry. 2016 ISHLT 36th Annual Meeting and Scientific Sessions. April 27-30, 2016; Washington, DC.
• Teuteberg, JJ. et al; Higher Rate of Hospitalizations for Infection and Cancer Then Rejection in Low Risk Heart Transplant Patients Followed by Gene Expression Profiling. 2016 ISHLT 36th Annual Meeting and Scientific Sessions. April 27-30, 2016; Washington, DC.
• Teuteberg, JJ. et al; Gene Expression Profiling Score and the Risk of Infection in Heart Transplant. 2016 American Transplant Congress. June 12, 2016; Boston, MA Poster
• Teuteberg, J., Shullo, MA., Rinde-Hoffman, D., Wigger, M., Wang, YS., Wolf, T., Arnold, PJ., Sninsky, J., Berman, P. Routine Surveillance of Heart Transplant Recipients with Gene Expression Profiling: Lack of an Impact of Race on Outcomes. 2017 American Transplant Congress. April 29-May 3, 2017; Chicago, IL. Poster
• Shah, P. et al: Outcomes with Gene Expression Profiling for Cardiac Transplant Recipients Within North America. 2016 ISHLT 36th Annual Meeting and Scientific Sessions. April 27-30, 2016; Washington, DC.
• Uriel, N. et al; Utility of Gene Expression (AlloMap Score) in Antibody Mediated Rejection Detection. 2016 ISHLT 36th Annual Meeting and Scientific Sessions. April 27-30, 2016; Washington, DC.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2013
• Primary Completion (Anticipated): February 1, 2020
• Study Completion (Anticipated): February 1, 2020

Study Registration Dates

• First Submitted: April 11, 2013
• First Submitted That Met QC Criteria: April 15, 2013
• First Posted (Estimate): April 16, 2013

Study Record Updates

• Last Update Posted (Actual): February 5, 2020
• Last Update Submitted That Met QC Criteria: February 3, 2020
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: prognosis; risk factors; heart transplantation; molecular diagnostics
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases
• Other Study ID Numbers: SN-C-00003