- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02597543
Stress Cardiac MRI for Evaluation of Nonspecific Allograft Dysfunction
Stress Cardiac MRI Using Regadenoson for Evaluation of Nonspecific Allograft Dysfunction
Study Overview
Status
Intervention / Treatment
Detailed Description
Adult heart-transplant patients, excluding those with a GFR less than 30 mL/min/1.73m2, contraindications to MRI and allergies to either regadenoson or gadolinium contrast, will be enrolled over 10 months. Patients will be recruited from UC San Diego and San Diego Veterans Affairs. The investigators will specifically enroll patients with nonspecific allograft dysfunction and patients with normal graft function.
Brief protocol:
Cardiac MRI is performed. Cine images in standard views are obtained. T2 mapping sequences are performed on short axis images. For stress imaging, intravenous regadenoson is given as a 0.4 mg bolus followed by a 5 mL saline flush. After 30 seconds, short-axis images are acquired for 30 consecutive heartbeats with administration of gadolinium. Rest imaging is performed 30 minutes after stress imaging. Lastly, late gadolinium enhancement images are obtained in standard views. Images are analyzed offline by a blinded independent reader. Patients will be followed for one month after enrollment for MACE.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
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California
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La Jolla, California, United States, 92037
- UC San Diego
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age greater than or equal to 18 years old.
- At least three months status post heart transplantation.
- Heart-transplant patients with normal graft function (left ventricular ejection fraction equal to or greater than 55%) and no prior history of clinically significant acute rejection episodes that required modification of the immunosuppressive regimen or cardiac allograft vasculopathy.
- Heart-transplant patients with nonspecific allograft dysfunction (left ventricular ejection fraction equal to or less than 50% AND decrease from post-transplant baseline ejection fraction by an absolute difference of 10% or greater, no formal diagnosis of allograft vasculopathy by coronary angiogram or coronary vascular ultrasonography, and no history of prior acute rejection episodes known to have decreased left ventricular ejection fraction to or less than 50%).
Exclusion Criteria:
- Biopsy proven acute rejection episode in the past 3 months.
- Patients with symptoms or signs of acute myocardial ischemia or recent acute coronary syndrome in the past 3 months.
- Uncontrolled obstructive ventilatory disease including asthma and COPD.
- Second or third degree AV nodal block.
- Sinus node dysfunction.
- Contraindications to MRI including pacemakers or implantable cardioverter-defibrillators.
- Renal dysfunction with an estimated GFR less than 30 mL/min/1.73m2.
- Prior adverse reaction to either regadenoson or gadolinium contrast. Prior adverse reaction to adenosine will be assessed on a case-by-case basis.
- Any invasive procedure, including endomyocardial biopsy and left coronary angiogram, performed within one week.
- Systolic blood pressure greater than 180 or less than 85 mmHg.
- Diastolic blood pressure greater than 120 or less than 40 mmHg.
- Resting heart rate greater than 120 or less than 45 beats per minute.
- Severe claustrophobia.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: DIAGNOSTIC
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: SINGLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Nonspecific allograft dysfunction
Patients with nonspecific allograft dysfunction will undergo stress cardiac MRI with regadenoson in addition to performing late gadolinium enhancement and obtaining mean segmental T1 values of the heart.
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For use in stress myocardial perfusion imaging.
Other Names:
For use in both perfusion imaging and late gadolinium enhancement.
Other Names:
Cardiac MRI will be the imaging modality for perfusion imaging, late gadolinium enhancement and obtaining mean T1 segmental values of the heart.
|
EXPERIMENTAL: Normal graft function
Patients with normal graft function will undergo stress cardiac MRI with regadenoson in addition to performing late gadolinium enhancement and obtaining mean segmental T1 values of the heart.
|
For use in stress myocardial perfusion imaging.
Other Names:
For use in both perfusion imaging and late gadolinium enhancement.
Other Names:
Cardiac MRI will be the imaging modality for perfusion imaging, late gadolinium enhancement and obtaining mean T1 segmental values of the heart.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Myocardial Perfusion Reserve
Time Frame: Range of 1 to 12 years after heart transplantation for subjects and an average of 4 years after heart-transplantation.
|
Myocardial perfusion reserve calculates the increase in myocardial perfusion after stress in comparison to rest.
Outcome measure time frame specifies when the myocardial perfusion reserve was obtained in relation to date of heart-transplant for each patient.
This was a one time measurement made after heart-transplantation.
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Range of 1 to 12 years after heart transplantation for subjects and an average of 4 years after heart-transplantation.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Myocardial Ischemia/Infarction
Time Frame: 10 months after enrollment (when cardiac MRI was performed)
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Myocardial ischemia or infarct occurring from time of enrollment (when cardiac MRI performed) over subsequent 10 month period.
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10 months after enrollment (when cardiac MRI was performed)
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Hospitalization for Cardiac Related Causes
Time Frame: 10 months after enrollment (from date of cardiac MRI)
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Hospitalization for cardiac related causes after enrollment.
Time frame after enrollment (date of cardiac MRI) was 10 months
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10 months after enrollment (from date of cardiac MRI)
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Re-transplantation
Time Frame: 10 months after enrollment (from date of cardiac MRI)
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Re-transplantation of the heart after enrollment (date of cardiac MRI).
Measured 10 months after enrollment.
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10 months after enrollment (from date of cardiac MRI)
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Late Gadolinium Enhancement
Time Frame: Range of 1 to 12 years after heart transplantation for subjects and an average of 4 years after heart-transplantation.
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Late gadolinium enhancement demonstrates myocardial scar by cardiac MRI.
This is measured the day of the cardiac MRI scan and is a one time measurement.
Time frame is measurement of late gadolinium enhancement from date of heart-transplantation.
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Range of 1 to 12 years after heart transplantation for subjects and an average of 4 years after heart-transplantation.
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Mean Segmental T1 Values of the Left Ventricle
Time Frame: Range of 1 to 12 years after heart transplantation for subjects and an average of 4 years after heart-transplantation.
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T1 values are obtained at the time of the cardiac MRI and indicate the amount of myocardial edema.
This was a one time measurement.
Outcome measure time frame indicates when T1 values of the left ventricle were obtained in relation to heart-transplantation.
|
Range of 1 to 12 years after heart transplantation for subjects and an average of 4 years after heart-transplantation.
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Paul J Kim, MD, Stanford University
Publications and helpful links
General Publications
- Stehlik J, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, Dobbels F, Kirk R, Rahmel AO, Hertz MI. The Registry of the International Society for Heart and Lung Transplantation: Twenty-eighth Adult Heart Transplant Report--2011. J Heart Lung Transplant. 2011 Oct;30(10):1078-94. doi: 10.1016/j.healun.2011.08.003. No abstract available.
- Berry GJ, Angelini A, Burke MM, Bruneval P, Fishbein MC, Hammond E, Miller D, Neil D, Revelo MP, Rodriguez ER, Stewart S, Tan CD, Winters GL, Kobashigawa J, Mehra MR. The ISHLT working formulation for pathologic diagnosis of antibody-mediated rejection in heart transplantation: evolution and current status (2005-2011). J Heart Lung Transplant. 2011 Jun;30(6):601-11. doi: 10.1016/j.healun.2011.02.015. No abstract available.
- Costanzo MR, Dipchand A, Starling R, Anderson A, Chan M, Desai S, Fedson S, Fisher P, Gonzales-Stawinski G, Martinelli L, McGiffin D, Smith J, Taylor D, Meiser B, Webber S, Baran D, Carboni M, Dengler T, Feldman D, Frigerio M, Kfoury A, Kim D, Kobashigawa J, Shullo M, Stehlik J, Teuteberg J, Uber P, Zuckermann A, Hunt S, Burch M, Bhat G, Canter C, Chinnock R, Crespo-Leiro M, Delgado R, Dobbels F, Grady K, Kao W, Lamour J, Parry G, Patel J, Pini D, Towbin J, Wolfel G, Delgado D, Eisen H, Goldberg L, Hosenpud J, Johnson M, Keogh A, Lewis C, O'Connell J, Rogers J, Ross H, Russell S, Vanhaecke J; International Society of Heart and Lung Transplantation Guidelines. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. J Heart Lung Transplant. 2010 Aug;29(8):914-56. doi: 10.1016/j.healun.2010.05.034. No abstract available.
- Uretsky BF, Murali S, Reddy PS, Rabin B, Lee A, Griffith BP, Hardesty RL, Trento A, Bahnson HT. Development of coronary artery disease in cardiac transplant patients receiving immunosuppressive therapy with cyclosporine and prednisone. Circulation. 1987 Oct;76(4):827-34. doi: 10.1161/01.cir.76.4.827.
- Fang JC, Kinlay S, Beltrame J, Hikiti H, Wainstein M, Behrendt D, Suh J, Frei B, Mudge GH, Selwyn AP, Ganz P. Effect of vitamins C and E on progression of transplant-associated arteriosclerosis: a randomised trial. Lancet. 2002 Mar 30;359(9312):1108-13. doi: 10.1016/S0140-6736(02)08154-0.
- 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.
- Bhalodolia R, Cortese C, Graham M, Hauptman PJ. Fulminant acute cellular rejection with negative findings on endomyocardial biopsy. J Heart Lung Transplant. 2006 Aug;25(8):989-92. doi: 10.1016/j.healun.2006.04.002. Epub 2006 Jun 30.
- Miller CA, Sarma J, Naish JH, Yonan N, Williams SG, Shaw SM, Clark D, Pearce K, Stout M, Potluri R, Borg A, Coutts G, Chowdhary S, McCann GP, Parker GJ, Ray SG, Schmitt M. Multiparametric cardiovascular magnetic resonance assessment of cardiac allograft vasculopathy. J Am Coll Cardiol. 2014 Mar 4;63(8):799-808. doi: 10.1016/j.jacc.2013.07.119. Epub 2013 Dec 18.
- Marie PY, Angioi M, Carteaux JP, Escanye JM, Mattei S, Tzvetanov K, Claudon O, Hassan N, Danchin N, Karcher G, Bertrand A, Walker PM, Villemot JP. Detection and prediction of acute heart transplant rejection with the myocardial T2 determination provided by a black-blood magnetic resonance imaging sequence. J Am Coll Cardiol. 2001 Mar 1;37(3):825-31. doi: 10.1016/s0735-1097(00)01196-7.
- Butler CR, Thompson R, Haykowsky M, Toma M, Paterson I. Cardiovascular magnetic resonance in the diagnosis of acute heart transplant rejection: a review. J Cardiovasc Magn Reson. 2009 Mar 12;11(1):7. doi: 10.1186/1532-429X-11-7.
- Kubrich M, Petrakopoulou P, Kofler S, Nickel T, Kaczmarek I, Meiser BM, Reichart B, von Scheidt W, Weis M. Impact of coronary endothelial dysfunction on adverse long-term outcome after heart transplantation. Transplantation. 2008 Jun 15;85(11):1580-7. doi: 10.1097/TP.0b013e318170b4cd.
- Solberg OG, Ragnarsson A, Kvarsnes A, Endresen K, Kongsgard E, Aakhus S, Gullestad L, Stavem K, Aaberge L. Reference interval for the index of coronary microvascular resistance. EuroIntervention. 2014 Jan 22;9(9):1069-75. doi: 10.4244/EIJV9I9A181.
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1186278
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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