Graft RejectionEIMAGENCT00962377
A Comparison of AlloMap Molecular Testing and Traditional Biopsy-based Surveillance for Heart Transplant Rejection Early Post-transplantation
A study testing Endomyocardial biopsy and AlloMap Molecular Testing in people with Graft Rejection and Heart Diseases, run by XDx at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Graft Rejection, Heart Diseases
- What is being tested?
- Endomyocardial biopsy and AlloMap Molecular Testing
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2009to Dec 2011
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Heart transplant recipients who are 2-6 months (≥55 days -185 days) post-transplant at the time of the first study surveillance visit
- Age ≥ 18 years
- Left ventricular ejection fraction ≥ 50% by Echocardiography, Multiple Gated Acquisition (MUGA) scan, or ventriculography at study entry (baseline / enrollment study)
Who cannot join
- 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
- Rejection therapy for biopsy-proven ISHLT Grade 3A or higher during the preceding 2 months
Show all 15Show fewer
- 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
- 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 first study surveillance visit
- 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 first study surveillance visit
Trial locations and contacts
1 site in 1 country.
United States1 site
Cedars-Sinai Medical Center
Beverly Hills, California, 90211
About this study
Official title: Early Invasive Monitoring Attenuation Through Gene Expression (EIMAGE) Trial
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.
Read the 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.
- Conditions
- Graft Rejection, Heart Diseases
- Being tested
- Endomyocardial biopsy, AlloMap Molecular Testing
- Keywords
- molecular expression testing, right ventricular endomyocardial biopsy
- Medical subject headings
- Heart Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Endomyocardial biopsyProcedure or surgery
Also called EMB
Right ventricular endomyocardial biopsy in monitoring of asymptomatic heart transplant patients for acute cellular rejection
AlloMap Molecular TestingProcedure or surgery
Also called GEP
Gene expression profiling in the monitoring of asymptomatic heart transplant patients for acute cellular rejection.
| Study group | Role | What they receive |
|---|---|---|
| AlloMap Molecular testing | Other | Gene expression profiling in the monitoring of asymptomatic heart transplant patients for acute cellular rejection. Receives: Procedure: AlloMap Molecular Testing |
| Endomyocardial biopsy | Active comparator | Right ventricular endomyocardial biopsy in the monitoring of asymptomatic heart transplant patients for acute cellular rejection Receives: Procedure: Endomyocardial biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1.5 years
Secondary outcomes (9)
Time from enrollment to death from any cause, and cause of death.
Measured: 1.5 years
Number of biopsies performed.
Measured: 1.5 years
Time from study enrollment to biopsy-related complications, as well as the number and type of biopsy-related complications.
Measured: 1.5 years
QOL responses as collected from the SF-12 form
Measured: Enrollment and one year post-transplant
Biopsy-related patient preferences satisfaction using a non-validated survey
Measured: Enrollment and one year post transplant
Objective measurements of cardiac function
Measured: 1.5 years
Gene expression profiling scores and immunosuppressant doses
Measured: 1.5 years
Number of rejection episodes.
Measured: 1.5 years
Utilization of AlloMap or biopsy to manage corticosteroid weaning between month 6 and month 12 post-transplant.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2009 (estimated)
- Study startAug 2009
- Primary completionDec 2011 (estimated)
- Study completionDec 2011 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Graft RejectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- XDx
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Upen Patil, MD, Study director, XDx, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00962377
- Sponsor's protocol ID
- CA-0007
- Acronym
- EIMAGE
- Status last verified
- Dec 2010
- First submitted
- 19 Aug 2009
- Last updated
- 21 Dec 2010
- Results posted
- No
- Data monitoring committee
- No
Publications
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. doi: 10.1111/j.1600-6143.2005.01175.x.
PubMed 16433769Starling 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. doi: 10.1016/j.healun.2006.10.002. No abstract available.
PubMed 17178330Evans 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. doi: 10.1111/j.1600-6143.2005.00869.x.
PubMed 15888068Marboe 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. doi: 10.1016/j.healun.2005.04.001.
PubMed 15993777Pham 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 cardiac transplantation. N Engl J Med. 2010 May 20;362(20):1890-900. doi: 10.1056/NEJMoa0912965. Epub 2010 Apr 22.
PubMed 20413602
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Invasive Monitoring Attenuation Through Gene Expression (EIMAGE) Trial
- ClinicalTrials.gov ID
- NCT00962377
- Acronym / sponsor ID
- EIMAGE / CA-0007
- Conditions
- Graft Rejection, Heart Diseases
- Keywords
- molecular expression testing, right ventricular endomyocardial biopsy
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (actual)
- Lead sponsor
- XDxIndustry (pharma, biotech, devices)
- Study start
- Aug 2009
- Primary completion
- Dec 2011 (estimated)
- Study completion
- Dec 2011 (estimated)
- First posted
- 20 Aug 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AlloMap Molecular testing | Other | Procedure: AlloMap Molecular TestingGene expression profiling in the monitoring of asymptomatic heart transplant patients for acute cellular rejection. |
| Endomyocardial biopsy | Active comparator | Procedure: Endomyocardial biopsyRight ventricular endomyocardial biopsy in the monitoring of asymptomatic heart transplant patients for acute cellular rejection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Heart transplant recipients who are 2-6 months (≥55 days -185 days) post-transplant at the time of the first study surveillance visit
- Age ≥ 18 years
- Left ventricular ejection fraction ≥ 50% by Echocardiography, Multiple Gated Acquisition (MUGA) scan, or ventriculography at study entry (baseline / enrollment study)
Key exclusion criteria (15 listed)
- Any clinical signs of declining graft function:
- Rejection therapy for biopsy-proven ISHLT Grade 3A or higher during the preceding 2 months
- 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
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Endomyocardial biopsyAlso: EMBRight ventricular endomyocardial biopsy in monitoring of asymptomatic heart transplant patients for acute cellular rejection | Procedure or surgery | Endomyocardial biopsy |
| AlloMap Molecular TestingAlso: GEPGene expression profiling in the monitoring of asymptomatic heart transplant patients for acute cellular rejection. | Procedure or surgery | AlloMap Molecular testing |
Primary outcome
Event-Free Survival and intravascular ultrasound (IVUS) measures
Time frame: 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.
9 secondary outcomes
Time from enrollment to death from any cause, and cause of death.
Time frame: 1.5 years
Number of biopsies performed.
Time frame: 1.5 years
Time from study enrollment to biopsy-related complications, as well as the number and type of biopsy-related complications.
Time frame: 1.5 years
QOL responses as collected from the SF-12 form
Time frame: Enrollment and one year post-transplant
Biopsy-related patient preferences satisfaction using a non-validated survey
Time frame: Enrollment and one year post transplant
Objective measurements of cardiac function
Time frame: 1.5 years
Gene expression profiling scores and immunosuppressant doses
Time frame: 1.5 years
Number of rejection episodes.
Time frame: 1.5 years
Utilization of AlloMap or biopsy to manage corticosteroid weaning between month 6 and month 12 post-transplant.
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2010.
- Background: PubMed 16433769Deng 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. doi: 10.1111/j.1600-6143.2005.01175.x.
- Background: PubMed 17178330Starling 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. doi: 10.1016/j.healun.2006.10.002. No abstract available.
- Background: PubMed 15888068Evans 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. doi: 10.1111/j.1600-6143.2005.00869.x.
- Background: PubMed 15993777Marboe 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. doi: 10.1016/j.healun.2005.04.001.
- Results publication: PubMed 20413602Pham 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 cardiac transplantation. N Engl J Med. 2010 May 20;362(20):1890-900. doi: 10.1056/NEJMoa0912965. Epub 2010 Apr 22.
- Information on molecular expression testingLink provided by the sponsor.
- Sponsor's websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Upen Patil, MD study director
XDx, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Endomyocardial biopsy and AlloMap Molecular Testing in people with Graft Rejection and Heart Diseases, run by XDx at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Dec 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-Free Survival and intravascular ultrasound (IVUS) measures (time frame: 1.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00962377, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2010.