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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2010 by XDx.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
XDx
ClinicalTrials.gov Identifier:
NCT00962377
First received: August 19, 2009
Last updated: December 20, 2010
Last verified: December 2010
  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:


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:

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

Exclusion Criteria:

  1. 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
  2. Rejection therapy for biopsy-proven ISHLT Grade 3A or higher during the preceding 2 months
  3. 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
  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 first study surveillance visit
  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 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:
Publications:

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 April 17, 2014