IMAGE: A Comparison of AlloMap Molecular Testing and Traditional Biopsy-based Surveillance for Heart Transplant Rejection

NCT ID: NCT00351559

Last Updated: 2009-11-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

629 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-01-31

Study Completion Date

2009-10-31

Brief Summary

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This study is designed to evaluate the safety and efficacy of a leukocyte gene expression profiling method in the monitoring of asymptomatic heart transplant patients for acute rejection.

Detailed Description

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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. With a higher incidence of acute cellular rejection (ACR) in the first six months post-transplant, ACR continues to occur beyond the first year post-transplant. However, the optimal strategy for detecting rejection during this period of lower risk period for ACR is still controversial. 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).

Conditions

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Graft Rejection Heart Diseases

Keywords

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allograft rejection biopsy gene expression cardiac heart transplant

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Interventions

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AlloMap molecular expression testing

Intervention Type DEVICE

Right ventricular endomyocardial biopsy

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

1. Heart transplant recipients who are \> 6 months to 5 years (\> 6-60 months) post-transplant.
2. Age ≥ 18 years.
3. Stable outpatient being seen for routine monitoring of rejection. Stability is defined as absence of prior or current evidence of either severe cardiac allograft vasculopathy (CAV) or antibody-mediated rejection (AMR) with associated hemodynamic compromise.

1. Severe CAV is defined as either

* \> 50% left main stenosis;
* ≥ 50% stenosis in ≥ 2 primary vessels (proximal 1/3 or middle 1/3 of the LAD or LCx, RCA to takeoff of PDA in right-dominant coronary circulations) or
* Isolated branch stenoses of \> 50% in all 3 systems (diagonal branches, obtuse marginal branches, distal 1/3 of LAD or LCx, PDA, PLB, and RCA to takeoff of PDA in non-dominant systems).
2. AMR with associated hemodynamic compromise is defined as AMR (defined according to local criteria) with either

* A left ventricular ejection fraction (LVEF) ≤ 30% or at least 25% lower than the baseline value,
* A cardiac index \< 2 l/min/m2, or
* The use of inotropic agents to support circulation.
4. Left ventricular ejection fraction ≥ 45% by Echocardiography, Multiple Gated Acquisition (MUGA) scan, or ventriculography at study entry (baseline / enrollment study).

Exclusion Criteria

1. Patients \< 7 calendar months after heart transplantation.
2. Any clinical signs of declining graft function:

1. Symptoms of Congestive Heart Failure (CHF) at the enrollment visit.
2. Signs of decompensated heart failure, including the development of a new S3 gallop at the enrollment visit.
3. Elevated right heart pressures with diminished cardiac index \< 2.2 L/min/m2 that is new compared to a previous measurement within 6 months.
4. Decrease in LVEF as measured by echocardiography: ≥ 25% compared to prior measurement within 6 months.
3. Rejection therapy for biopsy-proven ISHLT Grade 3A or higher during the preceding 2 months.
4. Major changes in immunosuppression therapy within previous 30 days (e.g., discontinuation of calcineurin inhibitors, switch from mycophenolate mofetil to sirolimus or vice versa).
5. Unable to give written informed consent.
6. Patient receiving hematopoietic growth factors (e.g., Neupogen, Epogen) currently or during the previous 30 days.
7. Patients receiving ≥ 20 mg/day of prednisone equivalent corticosteroids at the time of enrollment.
8. Patient enrolled in a trial requiring routine surveillance endomyocardial biopsies.
9. Patient received transfusion within preceding 4 weeks.
10. Patients with end-stage renal disease requiring some form of renal replacement therapy (hemodialysis or peritoneal dialysis).
11. Pregnancy at the time of enrollment.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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XDx

INDUSTRY

Sponsor Role lead

Principal Investigators

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Hannah A Valantine, MD, MRCP, FACC

Role: STUDY_CHAIR

Stanford University

Michael Pham, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

VA Palo Alto Health Care System

Mario C Deng, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University, New York Presbyterian Hospital

Jeffrey J Teuteberg, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh Medical Center

A G Kfoury, MD

Role: PRINCIPAL_INVESTIGATOR

Intermountain Medical Center

Dale G Renlund, MD

Role: PRINCIPAL_INVESTIGATOR

Intermountain Medical Center

Randall C Starling, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Allen Anderson, MD

Role: PRINCIPAL_INVESTIGATOR

University of Chicago

Thomas Cappola, MD, ScM

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Andrew Kao, MD

Role: PRINCIPAL_INVESTIGATOR

Mid America Heart Institute - St. Luke's Hospital

William G Cotts, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Roberta C Bogaev, M.D., FACC, FACP

Role: PRINCIPAL_INVESTIGATOR

Texas Heart Institute at St. Luke's Episcopal Hospital

David Baran, MD

Role: PRINCIPAL_INVESTIGATOR

Newark Beth Israel Medical Center

Greg Ewald, MD

Role: PRINCIPAL_INVESTIGATOR

Barnes-Jewish Hospital

Locations

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VA Palo Alto Health Care System

Palo Alto, California, United States

Site Status

Stanford University Medical Center

Stanford, California, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Mid America Heart Institute - St. Luke's Hospital

Kansas City, Missouri, United States

Site Status

Barnes Jewish Hospital - Washington University

St Louis, Missouri, United States

Site Status

Newark Beth Israel Medical Center

Newark, New Jersey, United States

Site Status

Columbia University Medical Center - New York Presbyterian Hospital

New York, New York, United States

Site Status

The Cleveland Clinic

Cleveland, Ohio, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Texas Heart Institute at St. Luke's Episcopal Hospital

Houston, Texas, United States

Site Status

Intermountain Medical Center

Murray, Utah, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 16433769 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15888068 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15993777 (View on PubMed)

Pham MX, Deng MC, Kfoury AG, Teuteberg JJ, Starling RC, Valantine H. Molecular testing for long-term rejection surveillance in heart transplant recipients: design of the Invasive Monitoring Attenuation Through Gene Expression (IMAGE) trial. J Heart Lung Transplant. 2007 Aug;26(8):808-14. doi: 10.1016/j.healun.2007.05.017.

Reference Type BACKGROUND
PMID: 17692784 (View on PubMed)

Deng MC, Elashoff B, Pham MX, Teuteberg JJ, Kfoury AG, Starling RC, Cappola TP, Kao A, Anderson AS, Cotts WG, Ewald GA, Baran DA, Bogaev RC, Shahzad K, Hiller D, Yee J, Valantine HA; IMAGE Study Group. Utility of gene expression profiling score variability to predict clinical events in heart transplant recipients. Transplantation. 2014 Mar 27;97(6):708-14. doi: 10.1097/01.TP.0000443897.29951.cf.

Reference Type DERIVED
PMID: 24637869 (View on PubMed)

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.

Reference Type DERIVED
PMID: 20413602 (View on PubMed)

Related Links

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http://www.xdx.com

Sponsor's web site

Other Identifiers

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CA-0004

Identifier Type: -

Identifier Source: org_study_id