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

NCT00351559 | Completed

• 1 other identifier: CA-0004
• Study Type: interventional
• Target: 629
• Locations: 1 country
• Sites: 13

Brief Summary

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.

Conditions

Graft Rejection; Heart Diseases

Keywords

allograft; rejection; biopsy; gene; expression; cardiac; heart; transplant

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (3)

• 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

Interventions

AlloMap molecular expression testing DEVICE

Right ventricular endomyocardial biopsy PROCEDURE

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Heart transplant recipients who are \> 6 months to 5 years (\> 6-60 months) post-transplant.
• Age ≥ 18 years.
• 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.
• 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).
• 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.
• Left ventricular ejection fraction ≥ 45% by Echocardiography, Multiple Gated Acquisition (MUGA) scan, or ventriculography at study entry (baseline / enrollment study).

You may not qualify if:

• Patients \< 7 calendar months after heart transplantation.
• Any clinical signs of declining graft function:
• Symptoms of Congestive Heart Failure (CHF) at the enrollment 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 6 months.
• Decrease in LVEF as measured by echocardiography: ≥ 25% compared to prior measurement within 6 months.
• Rejection therapy for biopsy-proven ISHLT Grade 3A or higher during the preceding 2 months.
• 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 enrollment.
• 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 enrollment.

Sponsors & Collaborators

• XDx: lead

Study Sites (13)

VA Palo Alto Health Care System

Palo Alto, California, 94304, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Mid America Heart Institute - St. Luke's Hospital

Kansas City, Missouri, 64111, United States

Location

Barnes Jewish Hospital - Washington University

St Louis, Missouri, 63110, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

Columbia University Medical Center - New York Presbyterian Hospital

New York, New York, 10032, United States

Location

The Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Texas Heart Institute at St. Luke's Episcopal Hospital

Houston, Texas, 77030, United States

Location

Intermountain Medical Center

Murray, Utah, 84157, United States

Location

Related Publications (6)

• 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.

  PMID: 16433769 BACKGROUND

• 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.

  PMID: 15888068 BACKGROUND

• 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.

  PMID: 15993777 BACKGROUND

• 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.

  PMID: 17692784 BACKGROUND

• 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.

  PMID: 24637869 DERIVED

• 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.

  PMID: 20413602 DERIVED

Related Links

• Sponsor's web site

MeSH Terms

Conditions

Heart Diseases; Rejection, Psychology

Condition Hierarchy (Ancestors)

Cardiovascular Diseases; Social Behavior; Behavior

Study Officials

• Hannah A Valantine, MD, MRCP, FACC

  Stanford University

  STUDY CHAIR

• 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

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: July 11, 2006
• First Posted: July 13, 2006
• Study Start: January 1, 2005
• Study Completion: October 1, 2009
• Last Updated: November 20, 2009

Record last verified: 2009-11

Locations

US (13)