Clinical trial NCT01833195: Outcomes AlloMap Registry: the Long-term Management and Outcomes of Heart Transplant Recipients With AlloMap Testing
Official title: 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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cardiac Transplant Failure
Cardiac Transplant Rejection
Heart Diseases
Keywords: molecular diagnostics
heart transplantation
risk factors
prognosis
Lead sponsor: CareDx
Sponsor class: INDUSTRY
First posted: 2013-04-16
Enrollment: 2444
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Heart transplant patients

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Vital status of heart transplant recipient
timeFrame: 5 Years
Secondary outcomes:
measure: Surveillance visit schedules and patient management parameters
timeFrame: 5 Years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Beverly Hills
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Gainesville
country: United States
facility: University of Florida,
state: Florida
city: Hollywood
country: United States
facility: Memorial Regional Hospital
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent Medical Group
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Mid America Heart Institute - St. Luke's Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: Integris Baptist Medical Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Drexel University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor Research Institute
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor St. Lukes
state: Texas
city: Houston
country: United States
facility: Houston Methodist Research Institute
state: Texas
city: Murray
country: United States
facility: Intermountain Heart Institute
state: Utah
city: Falls Church
country: United States
facility: Inova Heart & Vascular Institute
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
Study officials:
affiliation: CareDx, Inc., Brisbane, CA
name: James P Yee, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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
citation: 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
citation: 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.
citation: 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.