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

November 18, 2009 updated by: XDx

Invasive Monitoring Attenuation Through Gene Expression (IMAGE) Trial

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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. 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).

Study Type

Interventional

Enrollment (Actual)

629

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94304
        • VA Palo Alto Health Care System
      • Stanford, California, United States, 94305
        • Stanford University Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60637
        • University of Chicago
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Mid America Heart Institute - St. Luke's Hospital
      • St. Louis, Missouri, United States, 63110
        • Barnes Jewish Hospital - Washington University
    • New Jersey
      • Newark, New Jersey, United States, 07112
        • Newark Beth Israel Medical Center
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center - New York Presbyterian Hospital
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • The Cleveland Clinic
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Medical Center
    • Texas
      • Houston, Texas, United States, 77030
        • Texas Heart Institute at St. Luke's Episcopal Hospital
    • Utah
      • Murray, Utah, United States, 84157
        • Intermountain Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time from study enrollment to the earliest date of decrease in left ventricle function (left ventricular ejection fraction [LVEF] decrease ≥ 25% from baseline)
Time from study enrollment to the development of clinically overt rejection (heart failure, hemodynamic compromise)
Time from study enrollment to death from any cause

Secondary Outcome Measures

Outcome Measure
Number of deaths and cause of death
Number of biopsies planned and performed
Time to and number of biopsy-related complications, including bleeding, perforation and tamponade requiring pericardiocentesis, worsening of tricuspid regurgitation (TR) by 1 grade above 2+ or new TR at least 3+ or greater

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

XDx

Investigators

  • Principal Investigator: Allen Anderson, MD, University of Chicago
  • Study Chair: Hannah A Valantine, MD, MRCP, FACC, Stanford University
  • Principal Investigator: Michael Pham, MD, MPH, VA Palo Alto Health Care System
  • Principal Investigator: Mario C Deng, MD, Columbia University, New York Presbyterian Hospital
  • Principal Investigator: Jeffrey J Teuteberg, MD, University of Pittsburgh Medical Center
  • Principal Investigator: A G Kfoury, MD, Intermountain Medical Center
  • Principal Investigator: Dale G Renlund, MD, Intermountain Medical Center
  • Principal Investigator: Randall C Starling, MD, MPH, The Cleveland Clinic
  • Principal Investigator: Thomas Cappola, MD, ScM, University of Pennsylvania
  • Principal Investigator: Andrew Kao, MD, Mid America Heart Institute - St. Luke's Hospital
  • Principal Investigator: William G Cotts, MD, Northwestern University
  • Principal Investigator: Roberta C Bogaev, M.D., FACC, FACP, Texas Heart Institute at St. Luke's Episcopal Hospital
  • Principal Investigator: David Baran, MD, Newark Beth Israel Medical Center
  • Principal Investigator: Greg Ewald, MD, Barnes-Jewish Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2005

Study Completion (Actual)

October 1, 2009

Study Registration Dates

First Submitted

July 11, 2006

First Submitted That Met QC Criteria

July 11, 2006

First Posted (Estimate)

July 13, 2006

Study Record Updates

Last Update Posted (Estimate)

November 20, 2009

Last Update Submitted That Met QC Criteria

November 18, 2009

Last Verified

November 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA-0004

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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