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

Sponsor

XDx (Industry)

Overall Status

Completed

CT.gov ID

NCT00351559

Collaborator

(none)

629

Enrollment

Locations

Duration (Months)

48.4

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Graft Rejection Heart Diseases	Device: AlloMap molecular expression testing Procedure: Right ventricular endomyocardial biopsy	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

629 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Invasive Monitoring Attenuation Through Gene Expression (IMAGE) Trial

Study Start Date :

Jan 1, 2005

Actual Study Completion Date :

Oct 1, 2009

Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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).

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Palo Alto Health Care System	Palo Alto	California	United States	94304
2	Stanford University Medical Center	Stanford	California	United States	94305
3	Northwestern University	Chicago	Illinois	United States	60611
4	University of Chicago	Chicago	Illinois	United States	60637
5	Mid America Heart Institute - St. Luke's Hospital	Kansas City	Missouri	United States	64111
6	Barnes Jewish Hospital - Washington University	St. Louis	Missouri	United States	63110
7	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
8	Columbia University Medical Center - New York Presbyterian Hospital	New York	New York	United States	10032
9	The Cleveland Clinic	Cleveland	Ohio	United States	44195
10	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
11	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
12	Texas Heart Institute at St. Luke's Episcopal Hospital	Houston	Texas	United States	77030
13	Intermountain Medical Center	Murray	Utah	United States	84157

Sponsors and Collaborators

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 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