A Comparison of AlloMap Molecular Testing and Traditional Biopsy-based Surveillance for Heart Transplant Rejection Early Post-transplantation

Heart Diseases Clinical Trial

— EIMAGE  

Official title:

Early Invasive Monitoring Attenuation Through Gene Expression (EIMAGE) Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00962377
• Other study ID #: CA-0007
• Status: Active, not recruiting
• Phase: N/A
• First received: August 19, 2009
• Last updated: December 20, 2010
• Start date: August 2009
• Est. completion date: December 2011

Study information

• Verified date: December 2010
• Source: XDx
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Graft Rejection
• Heart Diseases

Intervention

Procedure:
• Endomyocardial biopsy
Right ventricular endomyocardial biopsy in monitoring of asymptomatic heart transplant patients for acute cellular rejection
• AlloMap Molecular Testing
Gene expression profiling in the monitoring of asymptomatic heart transplant patients for acute cellular rejection.

Locations

Country	Name	City	State
United States	Cedars-Sinai Medical Center	Beverly Hills	California

Sponsors (1)

Lead Sponsor	Collaborator
XDx

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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 cardia — View Citation

Starling RC, Pham M, Valantine H, Miller L, Eisen H, Rodriguez ER, Taylor DO, Yamani MH, Kobashigawa J, McCurry K, Marboe C, Mehra MR, Zuckerman A, Deng MC; Working Group on Molecular Testing in Cardiac Transplantation. Molecular testing in the management of cardiac transplant recipients: initial clinical experience. J Heart Lung Transplant. 2006 Dec;25(12):1389-95. Review. Erratum in: J Heart Lung Transplant. 2007 Feb;26(2):204. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-Free Survival and intravascular ultrasound (IVUS) measures	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.	1.5 years	No
Secondary	Time from enrollment to death from any cause, and cause of death.		1.5 years	No
Secondary	Number of biopsies performed.		1.5 years	No
Secondary	Time from study enrollment to biopsy-related complications, as well as the number and type of biopsy-related complications.		1.5 years	No
Secondary	QOL responses as collected from the SF-12 form		Enrollment and one year post-transplant	No
Secondary	Biopsy-related patient preferences satisfaction using a non-validated survey		Enrollment and one year post transplant	No
Secondary	Objective measurements of cardiac function		1.5 years	No
Secondary	Gene expression profiling scores and immunosuppressant doses		1.5 years	No
Secondary	Number of rejection episodes.		1.5 years	No
Secondary	Utilization of AlloMap or biopsy to manage corticosteroid weaning between month 6 and month 12 post-transplant.		6 months	No

External Links

•   Sponsor's website