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

Not Applicable

Completed

• Conditions: Graft Rejection; Heart Diseases

• Registration Number: NCT00351559
• Lead Sponsor: XDx

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.

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 Timeline

• Study Start: 2005-01
• Study First Submitted: 2006-07-11
• Study First Submitted QC: 2006-07-11
• Study First Posted: 2006-07-13
• Study Completion: 2009-10
• Status Verified: 2009-11
• Last Update Submitted: 2009-11-18
• Last Update Posted: 2009-11-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 629

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (13)

Newark Beth Israel Medical Center; 🇺🇸 Newark, New Jersey, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Texas Heart Institute at St. Luke's Episcopal Hospital; 🇺🇸 Houston, Texas, United States

Columbia University Medical Center - New York Presbyterian Hospital; 🇺🇸 New York, New York, United States

Mid America Heart Institute - St. Luke's Hospital; 🇺🇸 Kansas City, Missouri, United States

University of Chicago; 🇺🇸 Chicago, Illinois, United States

The Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Barnes Jewish Hospital - Washington University; 🇺🇸 St. Louis, Missouri, United States

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

VA Palo Alto Health Care System; 🇺🇸 Palo Alto, California, United States

Stanford University Medical Center; 🇺🇸 Stanford, California, United States

Intermountain Medical Center; 🇺🇸 Murray, Utah, United States