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Stress Cardiac MRI for Evaluation of Nonspecific Allograft Dysfunction

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ClinicalTrials.gov Identifier: NCT02597543
Recruitment Status : Completed
First Posted : November 5, 2015
Results First Posted : August 22, 2017
Last Update Posted : August 22, 2017
Sponsor:
Collaborator:
Astellas Pharma Inc
Information provided by (Responsible Party):
Paul Kim, Stanford University

Brief Summary:
The investigators will use cardiac MRI to measure the myocardial perfusion reserve and amount of myocardial edema and fibrosis in heart-transplant patients with nonspecific allograft dysfunction in contrast to those with normal graft function. The investigators hypothesize that patients with nonspecific allograft dysfunction will demonstrate decreased myocardial perfusion reserve, related to microvascular allograft vasculopathy, compared to those with normal graft function.

Condition or disease Intervention/treatment Phase
Heart Transplant Acute Graft Rejection Chronic Graft Rejection Drug: Regadenoson Drug: Gadolinium Procedure: Cardiac MRI Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: Stress Cardiac MRI Using Regadenoson for Evaluation of Nonspecific Allograft Dysfunction
Study Start Date : November 2015
Actual Primary Completion Date : June 30, 2016
Actual Study Completion Date : June 30, 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Regadenoson

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.
Drug: Regadenoson
For use in stress myocardial perfusion imaging.
Other Name: Lexiscan

Drug: Gadolinium
For use in both perfusion imaging and late gadolinium enhancement.
Other Name: Magnevist

Procedure: Cardiac MRI
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.
Drug: Regadenoson
For use in stress myocardial perfusion imaging.
Other Name: Lexiscan

Drug: Gadolinium
For use in both perfusion imaging and late gadolinium enhancement.
Other Name: Magnevist

Procedure: Cardiac MRI
Cardiac MRI will be the imaging modality for perfusion imaging, late gadolinium enhancement and obtaining mean T1 segmental values of the heart.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Myocardial Ischemia/Infarction [ Time Frame: 10 months after enrollment (when cardiac MRI was performed) ]
    Myocardial ischemia or infarct occurring from time of enrollment (when cardiac MRI performed) over subsequent 10 month period.

  2. Hospitalization for Cardiac Related Causes [ Time Frame: 10 months after enrollment (from date of cardiac MRI) ]
    Hospitalization for cardiac related causes after enrollment. Time frame after enrollment (date of cardiac MRI) was 10 months

  3. Re-transplantation [ Time Frame: 10 months after enrollment (from date of cardiac MRI) ]
    Re-transplantation of the heart after enrollment (date of cardiac MRI). Measured 10 months after enrollment.

  4. 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. ]
    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.

  5. 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. ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02597543


Locations
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United States, California
UC San Diego
La Jolla, California, United States, 92037
Sponsors and Collaborators
Paul Kim
Astellas Pharma Inc
Investigators
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Principal Investigator: Paul J Kim, MD Stanford University
Publications:
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.

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Responsible Party: Paul Kim, Cardiology Fellow, Stanford University
ClinicalTrials.gov Identifier: NCT02597543    
Other Study ID Numbers: 1186278
First Posted: November 5, 2015    Key Record Dates
Results First Posted: August 22, 2017
Last Update Posted: August 22, 2017
Last Verified: July 2017
Keywords provided by Paul Kim, Stanford University:
heart transplantation
cardiac MRI
graft rejection
nonspecific allograft dysfunction
allograft vasculopathy
Additional relevant MeSH terms:
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Regadenoson
Adenosine A2 Receptor Agonists
Purinergic P1 Receptor Agonists
Purinergic Agonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs