Graft Rejection, Heart Diseases
Conditions
Keywords
molecular expression testing, right ventricular endomyocardial biopsy
Brief summary
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.
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.
Interventions
PROCEDUREEndomyocardial biopsy
Right ventricular endomyocardial biopsy in monitoring of asymptomatic heart transplant patients for acute cellular rejection
PROCEDUREAlloMap Molecular Testing
Gene expression profiling in the monitoring of asymptomatic heart transplant patients for acute cellular rejection.
Sponsors
XDx
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-Free Survival and intravascular ultrasound (IVUS) measures | 1.5 years | 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
| Measure | Time frame |
|---|---|
| Number of biopsies performed. | 1.5 years |
| Time from study enrollment to biopsy-related complications, as well as the number and type of biopsy-related complications. | 1.5 years |
| QOL responses as collected from the SF-12 form | Enrollment and one year post-transplant |
| Biopsy-related patient preferences satisfaction using a non-validated survey | Enrollment and one year post transplant |
| Time from enrollment to death from any cause, and cause of death. | 1.5 years |
| Gene expression profiling scores and immunosuppressant doses | 1.5 years |
| Number of rejection episodes. | 1.5 years |
| Utilization of AlloMap or biopsy to manage corticosteroid weaning between month 6 and month 12 post-transplant. | 6 months |
| Objective measurements of cardiac function | 1.5 years |
Countries
United States
Outcome results
None listed