Graft Rejection, Heart Diseases
Conditions
Keywords
allograft, rejection, biopsy, gene, expression, cardiac, heart, transplant
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).
Interventions
DEVICEAlloMap molecular expression testing
PROCEDURERight ventricular endomyocardial biopsy
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
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
United States
Outcome results
None listed