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

Primary Purpose

Graft Rejection, Heart Diseases

Status

Unknown status

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Endomyocardial biopsy

AlloMap Molecular Testing

About this trial

This is an interventional diagnostic trial for Graft Rejection focused on measuring molecular expression testing, right ventricular endomyocardial biopsy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Cedars-Sinai Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Active Comparator

Arm Label

AlloMap Molecular testing

Endomyocardial biopsy

Arm Description

Gene expression profiling in the monitoring of asymptomatic heart transplant patients for acute cellular rejection.

Right ventricular endomyocardial biopsy in the monitoring of asymptomatic heart transplant patients for acute cellular rejection

Outcomes

Primary Outcome Measures

Event-Free Survival and intravascular ultrasound (IVUS) measures

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.

Number of biopsies performed.

Time from study enrollment to biopsy-related complications, as well as the number and type of biopsy-related complications.

QOL responses as collected from the SF-12 form

Biopsy-related patient preferences satisfaction using a non-validated survey

Objective measurements of cardiac function

Gene expression profiling scores and immunosuppressant doses

Number of rejection episodes.

Utilization of AlloMap or biopsy to manage corticosteroid weaning between month 6 and month 12 post-transplant.

Full Information

NCT ID

NCT00962377

First Posted

August 19, 2009

Last Updated

December 20, 2010

Sponsor

XDx

1. Study Identification

Unique Protocol Identification Number

NCT00962377

Brief Title

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

Acronym

EIMAGE

Official Title

Early Invasive Monitoring Attenuation Through Gene Expression (EIMAGE) Trial

Study Type

Interventional

2. Study Status

Record Verification Date

December 2010

Overall Recruitment Status

Unknown status

Study Start Date

August 2009 (undefined)

Primary Completion Date

December 2011 (Anticipated)

Study Completion Date

December 2011 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor

XDx

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Graft Rejection, Heart Diseases

Keywords

molecular expression testing, right ventricular endomyocardial biopsy

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AlloMap Molecular testing

Arm Type

Other

Arm Description

Gene expression profiling in the monitoring of asymptomatic heart transplant patients for acute cellular rejection.

Arm Title

Endomyocardial biopsy

Arm Type

Active Comparator

Arm Description

Right ventricular endomyocardial biopsy in the monitoring of asymptomatic heart transplant patients for acute cellular rejection

Intervention Type

Procedure

Intervention Name(s)

Endomyocardial biopsy

Other Intervention Name(s)

EMB

Intervention Description

Right ventricular endomyocardial biopsy in monitoring of asymptomatic heart transplant patients for acute cellular rejection

Intervention Type

Procedure

Intervention Name(s)

AlloMap Molecular Testing

Other Intervention Name(s)

GEP

Intervention Description

Gene expression profiling in the monitoring of asymptomatic heart transplant patients for acute cellular rejection.

Primary Outcome Measure Information:

Title

Event-Free Survival and intravascular ultrasound (IVUS) measures

Description

Time Frame

1.5 years

Secondary Outcome Measure Information:

Title

Time from enrollment to death from any cause, and cause of death.

Time Frame

1.5 years

Title

Number of biopsies performed.

Time Frame

1.5 years

Title

Time from study enrollment to biopsy-related complications, as well as the number and type of biopsy-related complications.

Time Frame

1.5 years

Title

QOL responses as collected from the SF-12 form

Time Frame

Enrollment and one year post-transplant

Title

Biopsy-related patient preferences satisfaction using a non-validated survey

Time Frame

Enrollment and one year post transplant

Title

Objective measurements of cardiac function

Time Frame

1.5 years

Title

Gene expression profiling scores and immunosuppressant doses

Time Frame

1.5 years

Title

Number of rejection episodes.

Time Frame

1.5 years

Title

Utilization of AlloMap or biopsy to manage corticosteroid weaning between month 6 and month 12 post-transplant.

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Upen Patil, MD

Organizational Affiliation

XDx, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Cedars-Sinai Medical Center

City

Beverly Hills

State/Province

California

ZIP/Postal Code

90211

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

16433769

Citation

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. doi: 10.1111/j.1600-6143.2005.01175.x.

Results Reference

background

PubMed Identifier

17178330

Citation

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. doi: 10.1016/j.healun.2006.10.002. No abstract available. Erratum In: J Heart Lung Transplant. 2007 Feb;26(2):204.

Results Reference

background

PubMed Identifier

15888068

Citation

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. doi: 10.1111/j.1600-6143.2005.00869.x.

Results Reference

background

PubMed Identifier

15993777

Citation

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. doi: 10.1016/j.healun.2005.04.001.

Results Reference

background

PubMed Identifier

20413602

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.

Results Reference

result

Links:

URL

http://www.xdx.com/allomap/

Description

Information on molecular expression testing

URL

http://xdx.com/

Description

Sponsor's website

Learn more about this trial

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

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