A Comparison of AlloMap Molecular Testing and Traditional Biopsy-based Surveillance for Heart Transplant Rejection Early Post-transplantation - Full Text View

Purpose

This study is designed to evaluate the safety and efficacy of a peripheral blood mononuclear cell gene expression profiling method (AlloMap) in monitoring asymptomatic heart transplant patients for acute rejection beginning 2-6 months(≥ 55-185 days) after transplantation.

Condition	Intervention
Graft Rejection Heart Diseases	Procedure: Endomyocardial biopsy Procedure: AlloMap Molecular Testing

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Diagnostic
Official Title:	Early Invasive Monitoring Attenuation Through Gene Expression (EIMAGE) Trial

Resource links provided by NLM:

MedlinePlus related topics: Heart Diseases Heart Transplantation

U.S. FDA Resources

Further study details as provided by XDx:

Primary Outcome Measures:

Event-Free Survival and intravascular ultrasound (IVUS) measures [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
Event-Free Survival (EFS) is a composite of: the development of hemodynamic compromise with rejection, allograft dysfunction (hemodynamic compromise without histologically confirmed rejection), death from any cause, or re-transplantation.

IVUS co-primary endpoint: maximal intimal thickness of the coronary arteries from baseline (measured at 6 weeks ± 30 days) to month 12 of ≥0.5mm, as measured by IVUS.

Secondary Outcome Measures:

Time from enrollment to death from any cause, and cause of death. [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
Number of biopsies performed. [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
Time from study enrollment to biopsy-related complications, as well as the number and type of biopsy-related complications. [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
QOL responses as collected from the SF-12 form [ Time Frame: Enrollment and one year post-transplant ] [ Designated as safety issue: No ]
Biopsy-related patient preferences satisfaction using a non-validated survey [ Time Frame: Enrollment and one year post transplant ] [ Designated as safety issue: No ]
Objective measurements of cardiac function [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
Gene expression profiling scores and immunosuppressant doses [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
Number of rejection episodes. [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
Utilization of AlloMap or biopsy to manage corticosteroid weaning between month 6 and month 12 post-transplant. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment:	40
Study Start Date:	August 2009
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
AlloMap Molecular testing Gene expression profiling in the monitoring of asymptomatic heart transplant patients for acute cellular rejection.	Procedure: AlloMap Molecular Testing Gene expression profiling in the monitoring of asymptomatic heart transplant patients for acute cellular rejection. Other Name: GEP
Active Comparator: Endomyocardial biopsy Right ventricular endomyocardial biopsy in the monitoring of asymptomatic heart transplant patients for acute cellular rejection	Procedure: Endomyocardial biopsy Right ventricular endomyocardial biopsy in monitoring of asymptomatic heart transplant patients for acute cellular rejection Other Name: EMB

Detailed Description:

Cardiac allograft rejection is experienced by 20-50% of patients at least once during the first year after cardiac transplantation under the present immunosuppression regimens. The standard for rejection surveillance has been the endomyocardial biopsy (EMB). However, EMB is invasive, causes morbidity, and is subject to sampling error and inter-observer variability.

Gene expression profiling (GEP), with its high negative predictive value (NPV) for acute cellular rejection (ACR), appears to be well suited to identify low-risk patients who can be safely managed without routine invasive endomyocardial biopsy (EMB).

The Invasive Monitoring Attenuation through Gene Expression (IMAGE) multicenter study was conducted between the years 2005-2009 and studied patients who were >6 months-5 years post transplant. The IMAGE study demonstrated that the clinical outcome of heart transplant patients managed with AlloMap® was noninferior to patients managed with EMB. The EIMAGE study expands the time window under study to include patients who are 2 months (≥ 55 days) post-transplant. This earlier time frame of study is the primary difference between the EIMAGE study and the IMAGE study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Heart transplant recipients who are 2-6 months (≥55 days -185 days) post-transplant at the time of the first study surveillance visit
Age ≥ 18 years
Left ventricular ejection fraction ≥ 50% by Echocardiography, Multiple Gated Acquisition (MUGA) scan, or ventriculography at study entry (baseline / enrollment study)

Exclusion Criteria:

Any clinical signs of declining graft function:
- Symptoms of Congestive Heart Failure (CHF) at the first study surveillance visit
- Signs of decompensated heart failure, including the development of a new S3 gallop at the enrollment visit
- Elevated right heart pressures with diminished cardiac index < 2.2 L/min/m2 that is new compared to a previous measurement within 2 months
- Decrease in LVEF as measured by echocardiography: ≥ 25% compared to prior measurement within 2 months
Rejection therapy for biopsy-proven ISHLT Grade 3A or higher during the preceding 2 months
Prior or current evidence of antibody-mediated rejection (AMR). AMR is defined according to the ISHLT 2004 Guidelines as positive histology and immunopathology (either immunofluorescence or immunoperoxidase) staining for AMR
Major changes in immunosuppression therapy within previous 30 days (e.g., discontinuation of calcineurin inhibitors, switch from mycophenolate mofetil to sirolimus or vice versa)
Unable to give written informed consent
Patient receiving hematopoietic growth factors (e.g., Neupogen, Epogen) currently or during the previous 30 days
Patients receiving ≥ 20 mg/day of prednisone equivalent corticosteroids at the time of first study surveillance visit
Patient enrolled in a trial requiring routine surveillance endomyocardial biopsies
Patient received transfusion within preceding 4 weeks
Patients with end-stage renal disease requiring some form of renal replacement therapy (hemodialysis or peritoneal dialysis)
Pregnancy at the time of first study surveillance visit

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00962377

Locations

United States, California
Cedars-Sinai Medical Center
Beverly Hills, California, United States, 90211

Sponsors and Collaborators

XDx

Investigators

Study Director:

Upen Patil, MD

XDx, Inc.

More Information

Additional Information:

Information on molecular expression testing This link exits the ClinicalTrials.gov site

Sponsor's website This link exits the ClinicalTrials.gov site

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. Epub 2010 Apr 22.

Deng MC, Eisen HJ, Mehra MR, Billingham M, Marboe CC, Berry G, Kobashigawa J, Johnson FL, Starling RC, Murali S, Pauly DF, Baron H, Wohlgemuth JG, Woodward RN, Klingler TM, Walther D, Lal PG, Rosenberg S, Hunt S; CARGO Investigators. Noninvasive discrimination of rejection in cardiac allograft recipients using gene expression profiling. Am J Transplant. 2006 Jan;6(1):150-60.

Starling RC, Pham M, Valantine H, Miller L, Eisen H, Rodriguez ER, Taylor DO, Yamani MH, Kobashigawa J, McCurry K, Marboe C, Mehra MR, Zuckerman A, Deng MC; Working Group on Molecular Testing in Cardiac Transplantation. Molecular testing in the management of cardiac transplant recipients: initial clinical experience. J Heart Lung Transplant. 2006 Dec;25(12):1389-95. Review. No abstract available. Erratum in: J Heart Lung Transplant. 2007 Feb;26(2):204.

Evans RW, Williams GE, Baron HM, Deng MC, Eisen HJ, Hunt SA, Khan MM, Kobashigawa JA, Marton EN, Mehra MR, Mital SR. The economic implications of noninvasive molecular testing for cardiac allograft rejection. Am J Transplant. 2005 Jun;5(6):1553-8.

Marboe CC, Billingham M, Eisen H, Deng MC, Baron H, Mehra M, Hunt S, Wohlgemuth J, Mahmood I, Prentice J, Berry G. Nodular endocardial infiltrates (Quilty lesions) cause significant variability in diagnosis of ISHLT Grade 2 and 3A rejection in cardiac allograft recipients. J Heart Lung Transplant. 2005 Jul;24(7 Suppl):S219-26.

Responsible Party:	Debbie Pieretti, Sr. Director Clinical Operations, XDx, Inc.
ClinicalTrials.gov Identifier:	NCT00962377 History of Changes
Other Study ID Numbers:	CA-0007
Study First Received:	August 19, 2009
Last Updated:	December 20, 2010
Health Authority:	United States: Institutional Review Board

Keywords provided by XDx:

molecular expression testing
right ventricular endomyocardial biopsy

Additional relevant MeSH terms:

Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on May 23, 2013

A Comparison of AlloMap Molecular Testing and Traditional Biopsy-based Surveillance for Heart Transplant Rejection Early Post-transplantation (EIMAGE)