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Graft RejectionNCT00351559

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

A study testing AlloMap molecular expression testing and Right ventricular endomyocardial biopsy in people with Graft Rejection and Heart Diseases, run by XDx at 13 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Graft Rejection, Heart Diseases
What is being tested?
AlloMap molecular expression testing and Right ventricular endomyocardial biopsy
How many people
629 participants
Where
13 sitesUnited States
Study dates
Jan 2005to Oct 2009
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
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Heart transplant recipients who are > 6 months to 5 years (> 6-60 months) post-transplant.
  • Age ≥ 18 years.
  • 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.
  • 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
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  • 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).
  • 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.
  • Left ventricular ejection fraction ≥ 45% by Echocardiography, Multiple Gated Acquisition (MUGA) scan, or ventriculography at study entry (baseline / enrollment study).

Who cannot join

  • Patients < 7 calendar months after heart transplantation.
  • Any clinical signs of declining graft function:
  • Symptoms of Congestive Heart Failure (CHF) at the enrollment 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 6 months.
  • Decrease in LVEF as measured by echocardiography: ≥ 25% compared to prior measurement within 6 months.
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  • Rejection therapy for biopsy-proven ISHLT Grade 3A or higher during the preceding 2 months.
  • 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 enrollment.
  • 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 enrollment.

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United States13 sites
  • Northwestern University

    Chicago, Illinois, 60611

  • University of Chicago

    Chicago, Illinois, 60637

  • The Cleveland Clinic

    Cleveland, Ohio, 44195

  • Texas Heart Institute at St. Luke's Episcopal Hospital

    Houston, Texas, 77030

  • Mid America Heart Institute - St. Luke's Hospital

    Kansas City, Missouri, 64111

  • Intermountain Medical Center

    Murray, Utah, 84157

  • Columbia University Medical Center - New York Presbyterian Hospital

    New York, New York, 10032

  • Newark Beth Israel Medical Center

    Newark, New Jersey, 07112

  • VA Palo Alto Health Care System

    Palo Alto, California, 94304

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

  • Barnes Jewish Hospital - Washington University

    St Louis, Missouri, 63110

  • Stanford University Medical Center

    Stanford, California, 94305

Other trials in United States

About this study

Official title: Invasive Monitoring Attenuation Through Gene Expression (IMAGE) Trial

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.

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. 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).

Being tested
AlloMap molecular expression testing, Right ventricular endomyocardial biopsy
Keywords
allograft, rejection, biopsy, gene, expression, cardiac, heart, transplant
Medical subject headings
Heart Diseases, Rejection, Psychology

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AlloMap molecular expression testingDevice

  • Right ventricular endomyocardial biopsyProcedure or surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time from study enrollment to the earliest date of decrease in left ventricle function (left ventricular ejection fraction [LVEF] decrease ≥ 25% from baseline)

  2. Time from study enrollment to the development of clinically overt rejection (heart failure, hemodynamic compromise)

  3. Time from study enrollment to death from any cause

Secondary outcomes (3)
  1. Number of deaths and cause of death

  2. Number of biopsies planned and performed

  3. 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jul 2006 (estimated)
  2. Study startJan 2005
  3. Study completionOct 2009

Resources

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
629 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00351559
Sponsor's protocol ID
CA-0004
Status last verified
Nov 2009
First submitted
11 Jul 2006
Last updated
20 Nov 2009
Results posted
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 16433769
  • 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. doi: 10.1111/j.1600-6143.2005.00869.x.

    PubMed 15888068
  • 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. doi: 10.1016/j.healun.2005.04.001.

    PubMed 15993777
  • Pham MX, Deng MC, Kfoury AG, Teuteberg JJ, Starling RC, Valantine H. Molecular testing for long-term rejection surveillance in heart transplant recipients: design of the Invasive Monitoring Attenuation Through Gene Expression (IMAGE) trial. J Heart Lung Transplant. 2007 Aug;26(8):808-14. doi: 10.1016/j.healun.2007.05.017.

    PubMed 17692784
  • Deng MC, Elashoff B, Pham MX, Teuteberg JJ, Kfoury AG, Starling RC, Cappola TP, Kao A, Anderson AS, Cotts WG, Ewald GA, Baran DA, Bogaev RC, Shahzad K, Hiller D, Yee J, Valantine HA; IMAGE Study Group. Utility of gene expression profiling score variability to predict clinical events in heart transplant recipients. Transplantation. 2014 Mar 27;97(6):708-14. doi: 10.1097/01.TP.0000443897.29951.cf.

    PubMed 24637869
  • 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 cardiac transplantation. N Engl J Med. 2010 May 20;362(20):1890-900. doi: 10.1056/NEJMoa0912965. Epub 2010 Apr 22.

    PubMed 20413602

Questions about this trial

What is this clinical trial studying?

A study testing AlloMap molecular expression testing and Right ventricular endomyocardial biopsy in people with Graft Rejection and Heart Diseases, run by XDx at 13 sites 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 12 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: finished, as of the sponsor's last update on 20 Nov 2009. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Time from study enrollment to the earliest date of decrease in left ventricle function (left ventricular ejection fraction [LVEF] decrease ≥ 25% from baseline). The study lists 3 primary outcomes in all. 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 NCT00351559, which also lists 6 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 20 Nov 2009.

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