Study Summary
This trial will use MRI and cell sequencing to look for early evidence of heart transplant rejection and determine the underlying causes.
Treatment Effectiveness
Phase-Based Effectiveness
Phase 4
Study Objectives
1 Primary · 8 Secondary · Reporting Duration: 60 months
60 months
LGE %
LV end-diastolic volume index
LV mass index
LVEF
Major adverse cardiovascular events
Myocardial Perfusion Reserve
Number of stenotic microvasculopathy by histopathologic review of endomyocardial biopsy samples
Percentage of different T-cell subsets by single cell RNAseq
Rest and stress myocardial blood flow
extracellular volumes
myocardial strain rate
native T1 and T2 myocardial values
Trial Safety
Phase-Based Safety
This is further along than 85% of similar trials
Awards & Highlights
Drug Has Already Been Approved
The FDA has already approved this drug, and is just seeking more data.
No Placebo Group
All patients enrolled in this trial will receive the new treatment.
Pivotal Trial
The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.
All Individual Drugs Already Approved
Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.
Trial Design
4 Treatment Groups
ACR/AMR
1 of 4
Nonspecific allograft dysfunction
1 of 4
Normal graft function
1 of 4
Cardiac allograft vasculopathy
1 of 4
Experimental Treatment
376 Total Participants · 4 Treatment Groups
Primary Treatment: Regadenoson · No Placebo Group · Phase 4
ACR/AMR
Drug
Experimental Group · 1 Intervention: Regadenoson · Intervention Types: DrugNonspecific allograft dysfunction
Drug
Experimental Group · 1 Intervention: Regadenoson · Intervention Types: DrugNormal graft function
Drug
Experimental Group · 1 Intervention: Regadenoson · Intervention Types: DrugCardiac allograft vasculopathy
Drug
Experimental Group · 1 Intervention: Regadenoson · Intervention Types: DrugTreatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Regadenoson
FDA approved
Trial Logistics
Trial Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: 60 months
Who is running the clinical trial?
Paul KimLead Sponsor
1 Previous Clinical Trials
14 Total Patients Enrolled
Paul Kim, MDPrincipal Investigator - UC San Diego
Regents of the University of California - UCSD Medical Group, UCSD Medical Center-Hillcrest
3 Previous Clinical Trials
412 Total Patients Enrolled
Eligibility Criteria
Age 18+ · All Participants · 0 Total Inclusion Criteria
Mark “Yes” if the following statements are true for you:References
- Stehlik, Josef, Leah B. Edwards, Anna Y. Kucheryavaya, Christian Benden, Jason D. Christie, Fabienne Dobbels, Richard Kirk, Axel O. Rahmel, and Marshall I. Hertz. 2011. “The Registry of the International Society for Heart and Lung Transplantation: Twenty-eighth Adult Heart Transplant Report—2011”. The Journal of Heart and Lung Transplantation. Elsevier BV. doi:10.1016/j.healun.2011.08.003.
- Marie, Pierre Y, Michael Angioı̈, Jean P Carteaux, Jean M Escanye, Sophie Mattei, Kiril Tzvetanov, Olivier Claudon, et al.. 2001. “Detection and Prediction of Acute Heart Transplant Rejection with the Myocardial T2determination Provided by a Black-blood Magnetic Resonance Imaging Sequence”. Journal of the American College of Cardiology. Elsevier BV. doi:10.1016/s0735-1097(00)01196-7.
- Kübrich, Marion, Paraskevi Petrakopoulou, Sieglinde Kofler, Thomas Nickel, Ingo Kaczmarek, Bruno M. Meiser, Bruno Reichart, Wolfgang von Scheidt, and Michael Weis. 2008. “Impact of Coronary Endothelial Dysfunction on Adverse Long-term Outcome After Heart Transplantation”. Transplantation. Ovid Technologies (Wolters Kluwer Health). doi:10.1097/tp.0b013e318170b4cd.
- Uretsky, B F, S Murali, P S Reddy, B Rabin, A Lee, B P Griffith, R L Hardesty, A Trento, and H T Bahnson. 1987. “Development of Coronary Artery Disease in Cardiac Transplant Patients Receiving Immunosuppressive Therapy with Cyclosporine and Prednisone.”. Circulation. Ovid Technologies (Wolters Kluwer Health). doi:10.1161/01.cir.76.4.827.
- Pham, Michael X., Jeffrey J. Teuteberg, Abdallah G. Kfoury, Randall C. Starling, Mario C. Deng, Thomas P. Cappola, Andrew Kao, et al.. 2010. “Gene-expression Profiling for Rejection Surveillance After Cardiac Transplantation”. New England Journal of Medicine. Massachusetts Medical Society. doi:10.1056/nejmoa0912965.
- Berry, Gerald J., Annalisa Angelini, Margaret M. Burke, Patrick Bruneval, Michael C. Fishbein, Elizabeth Hammond, Dylan Miller, et al.. 2011. “The ISHLT Working Formulation for Pathologic Diagnosis of Antibody-mediated Rejection in Heart Transplantation: Evolution and Current Status (2005–2011)”. The Journal of Heart and Lung Transplantation. Elsevier BV. doi:10.1016/j.healun.2011.02.015.
- Bhalodolia, Rajeshkumar, Cherise Cortese, Michael Graham, and Paul J. Hauptman. 2006. “Fulminant Acute Cellular Rejection with Negative Findings on Endomyocardial Biopsy”. The Journal of Heart and Lung Transplantation. Elsevier BV. doi:10.1016/j.healun.2006.04.002.
- Costanzo, Maria Rosa, Maria Rosa Costanzo, Anne Dipchand, Randall Starling, Allen Anderson, Michael Chan, Shashank Desai, et al.. 2010. “The International Society of Heart and Lung Transplantation Guidelines for the Care of Heart Transplant Recipients”. The Journal of Heart and Lung Transplantation. Elsevier BV. doi:10.1016/j.healun.2010.05.034.
- Fang, James C, Scott Kinlay, John Beltrame, Hiroyuki Hikiti, Marco Wainstein, Dominik Behrendt, Jung Suh, et al.. 2002. “Effect of Vitamins C and E on Progression of Transplant-associated Arteriosclerosis: A Randomised Trial”. The Lancet. Elsevier BV. doi:10.1016/s0140-6736(02)08154-0.
- Butler, Craig R, Richard Thompson, Mark Haykowsky, Mustafa Toma, and Ian Paterson. 2009. “Cardiovascular Magnetic Resonance in the Diagnosis of Acute Heart Transplant Rejection: A Review”. Journal of Cardiovascular Magnetic Resonance. Springer Science and Business Media LLC. doi:10.1186/1532-429x-11-7.
- Solberg, Ole Geir, Asgrimur Ragnarsson, Anita Kvarsnes, Knut Endresen, Erik Kongsgård, Svend Aakhus, Lars Gullestad, Knut Stavem, and Lars Aaberge. 2014. “Reference Interval for the Index of Coronary Microvascular Resistance”. Eurointervention. Europa Digital & Publishing. doi:10.4244/eijv9i9a181.
- Miller, Christopher A., Jaydeep Sarma, Josephine H. Naish, Nizar Yonan, Simon G. Williams, Steven M. Shaw, David Clark, et al.. 2014. “Multiparametric Cardiovascular Magnetic Resonance Assessment of Cardiac Allograft Vasculopathy”. Journal of the American College of Cardiology. Elsevier BV. doi:10.1016/j.jacc.2013.07.119.
- 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.
- 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.
- 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.
- Paul Kim 2019. "Allograft Dysfunction in Heart Transplant". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03102125.
Frequently Asked Questions
How many participants are being welcomed into this trial?
"Affirmative, the clinical trial is still recruiting participants according to clinicaltrials.gov's records. This investigation was originally posted on October 1st 2019 and recently updated on November 3rd 2021 with a goal of enrolling 376 patients from one medical facility." - Anonymous Online Contributor
Unverified Answer
Is this pioneering clinical trial the first of its kind?
"Clinical studies of regadenoson commenced in 2014, with Astellas Scientific & Medical Affairs, Inc. sponsoring the first trial involving 300 participants. Subsequently approved by Phase 4 drug approval, 7 current trials are ongoing across 6 distinct countries and 12 cities." - Anonymous Online Contributor
Unverified Answer
Has the U.S Food and Drug Administration (FDA) validated the use of Regadenoson?
"Regadenoson is proven to be safe as evidenced by its Phase 4 status, and thus earned a score of 3 on our 1-3 scale." - Anonymous Online Contributor
Unverified Answer
Are there any other documented instances of Regadenoson being tested as a treatment?
"Presently, 7 clinical trials are researching the effects of Regadenoson with 0 conducted in Phase 3. Multiple locations across the United States are participating, particularly around Houston Texas; 20 sites total have been identified as possible places to conduct this medical research." - Anonymous Online Contributor
Unverified Answer
Are there any vacancies available in this clinical trial?
"This clinical trial, which was initially published on October 1st 2019 and revised November 3rd 2021 according to the information found at clinicaltrials.gov is actively looking for participants." - Anonymous Online Contributor
Unverified Answer