Stress Cardiac MRI for Evaluation of Nonspecific Allograft Dysfunction

NCT02597543 | Completed Phase 4 Results

• 1 other identifier: 1186278
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Transplant; Acute Graft Rejection; Chronic Graft Rejection

Keywords

heart transplantation; cardiac MRI; graft rejection; nonspecific allograft dysfunction; allograft vasculopathy

Outcome Measures

Primary Outcomes (1)

• Myocardial Perfusion Reserve

  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.

  Range of 1 to 12 years after heart transplantation for subjects and an average of 4 years after heart-transplantation.

Secondary Outcomes (5)

• Myocardial Ischemia/Infarction

  10 months after enrollment (when cardiac MRI was performed)

• Hospitalization for Cardiac Related Causes

  10 months after enrollment (from date of cardiac MRI)

• Re-transplantation

  10 months after enrollment (from date of cardiac MRI)

• Late Gadolinium Enhancement

  Range of 1 to 12 years after heart transplantation for subjects and an average of 4 years after heart-transplantation.

• Mean Segmental T1 Values of the Left Ventricle

  Range of 1 to 12 years after heart transplantation for subjects and an average of 4 years after heart-transplantation.

Study Arms (2)

Nonspecific allograft dysfunction

EXPERIMENTAL

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; Drug: Gadolinium; Procedure: Cardiac MRI

Normal graft function

EXPERIMENTAL

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; Drug: Gadolinium; Procedure: Cardiac MRI

Interventions

Regadenoson DRUG

For use in stress myocardial perfusion imaging.

Also known as: Lexiscan

Nonspecific allograft dysfunction; Normal graft function

Gadolinium DRUG

For use in both perfusion imaging and late gadolinium enhancement.

Also known as: Magnevist

Nonspecific allograft dysfunction; Normal graft function

Cardiac MRI PROCEDURE

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

Nonspecific allograft dysfunction; Normal graft function

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Paul Kim: lead
• Astellas Pharma Inc: collaborator

Study Sites (1)

UC San Diego

La Jolla, California, 92037, United States

Location

Related Publications (12)

• 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.

  PMID: 21962016 BACKGROUND

• 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.

  PMID: 21555100 BACKGROUND

• 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.

  PMID: 20643330 BACKGROUND

• 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.

  PMID: 3308166 BACKGROUND

• 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.

  PMID: 11943259 BACKGROUND

• 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.

  PMID: 20413602 BACKGROUND

• 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.

  PMID: 16890123 BACKGROUND

• 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.

  PMID: 24355800 BACKGROUND

• 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.

  PMID: 11693758 BACKGROUND

• 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.

  PMID: 19284612 BACKGROUND

• 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.

  PMID: 18551063 BACKGROUND

• 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.

  PMID: 24457279 BACKGROUND

MeSH Terms

Interventions

regadenoson; Gadolinium; Gadolinium DTPA

Intervention Hierarchy (Ancestors)

Lanthanoid Series Elements; Metals, Rare Earth; Elements; Inorganic Chemicals; Metals; Pentetic Acid; Polyamines; Amines; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Coordination Complexes

Results Point of Contact

• Title: Paul Kim, MD
• Organization: UCSD

pjk017@ucsd.edu

3104907217

Study Officials

• Paul J Kim, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Cardiology Fellow

Study Record Dates

• First Submitted: October 30, 2015
• First Posted: November 5, 2015
• Study Start: November 1, 2015
• Primary Completion: June 30, 2016
• Study Completion: June 30, 2016
• Last Updated: August 22, 2017
• Results First Posted: August 22, 2017

Record last verified: 2017-07

Locations

US (1)