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

This study has been completed.
Sponsor:
Information provided by:
XDx
ClinicalTrials.gov Identifier:
NCT00351559
First received: July 11, 2006
Last updated: November 18, 2009
Last verified: November 2009
  Purpose

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.


Condition Intervention
Graft Rejection
Heart Diseases
Device: AlloMap molecular expression testing
Procedure: Right ventricular endomyocardial biopsy

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

Resource links provided by NLM:


Further study details as provided by XDx:

Primary Outcome Measures:
  • 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:
  • 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

Enrollment: 629
Study Start Date: January 2005
Study Completion Date: October 2009
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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00351559

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

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00351559     History of Changes
Other Study ID Numbers: CA-0004
Study First Received: July 11, 2006
Last Updated: November 18, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by XDx:
allograft
rejection
biopsy
gene
expression
cardiac
heart
transplant

Additional relevant MeSH terms:
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on July 28, 2014