Clinical Trials Logo

Clinical Trial Summary

Cardiac transplantation is the ultimate treatment option for patients with end stage heart failure.

Cardiac allograft vasculopathy remains a leading cause of morbidity and mortality after transplantation.

Angiotensin converting enzyme inhibitors are used in less than one half of transplant recipients. Preliminary data suggest that angiotensin converting enzyme inhibitors retard the atherosclerotic plaque development that is the hallmark of cardiac allograft vasculopathy. Moreover, this class of drug appears to increase circulating endothelial progenitor cell number and has anti-inflammatory properties, both of which improve endothelial dysfunction, the key precursor to the development of cardiac allograft vasculopathy.

The objective of this project is to investigate the role of an angiotensin converting enzyme inhibitor, ramipril, in preventing the development of cardiac allograft vasculopathy. During the first month after cardiac transplantation subjects will undergo coronary angiography with intravascular ultrasound measurements of plaque volume in the left anterior descending coronary artery. Using a coronary pressure wire, epicardial artery and microvascular physiology will be assessed. Finally, endothelial function and mediators of endothelial function, including circulating endothelial progenitor cells, will be measured. Subjects will then be randomized in a double blind fashion to either ramipril or placebo. After 1 year, the above assessment will be repeated. The primary endpoint will be the development of cardiac allograft vasculopathy based on intravascular ultrasound-derived parameters. The second aim will be to assess the effect of ramipril on endothelial dysfunction early after transplantation. The final aim is to determine the impact of ramipril on coronary physiology early after transplantation.


Clinical Trial Description

During the first 4 years of this study, we plan to recruit patients within the first month after OHT. As has become routine at Stanford, study subjects will undergo baseline coronary angiography and IVUS assessment of their left anterior descending coronary artery. Coronary endothelial function will be assessed as well transmyocardial levels of ADMA and other mediators of endothelial function. Blood samples will be obtained for analyzing circulating EPC number and function. Epicardial and microvascular coronary physiology in the left anterior descending coronary artery will be determined by measuring FFR and IMR with a coronary pressure wire(in the adults only). Subjects will then be randomized to either the ACE I(Ramipril), or to placebo, in addition to their usual medications. During years 2 through 5 of this project, study subjects will undergo the above routine invasive assessments at 1 year after OHT. During the 5th year of this project, data analysis and manuscript preparation will occur.

Table 2. Patient Flowchart Time post OHT Event 0-4 Weeks Recruitment and enrollment 4-6 Weeks Baseline angiogram, endothelial function, coronary physiology and IVUS studies 4-6 (at time of baseline)Weeks Baseline blood sampling for circulating EPC studies 4-6 Weeks Randomization to ramipril or placebo to begin one week after baseline studies 5-7 Weeks Titration up of ramipril or placebo Month 3 and month 6: blood sampling for EPC studies. 11-13 Months 1 year angiogram, endothelial function, coronary physiology and IVUS studies 11-13 Months 1 year blood sampling for circulating EPC studies The primary endpoint of the study will be change in plaque volume as determined by IVUS analysis at baseline and 1 year later, between those treated with ramipril compared to those treated with placebo.

Secondary endpoints will include change in circulating EPC number and function, change in ADMA levels,change in coronary endothelium-dependent vasodilation, and change in coronary physiology (FFR and IMR)from baseline to 1 year. Although there are multiple potential mechanisms by which ACE I might reduce CAV, evaluating each of these is beyond the scope of this project. For this reason, we will focus on the likely common final pathway of endothelial dysfunction mediated by dysregulation of ADMA and NOS, as well as changes in EPCs. If this study shows a benefit to ACE I therapy in this population, the goal of future studies will be to determine the exact mechanism by which this occurs and to perform a large, multicenter study comparing ACE I to placebo with hard clinical endpoints. Study visits include two major time points 1) baseline angiogram and IVUS which include recording of angiographic data, lab data, clinical data. 2)assessment at the usual follow up periods post transplant, and these data points will also be collected for research purposes. after base line which usually occurs one month post transplant plus or minus 2 weeks. F/u = q 2 weeks until two months out from tx, then once per month until six months out from TX, then every two months until the patient is 12 months out from TX. Each routine f/u visit includes a physical exam,vital signs, echocardiogram, chest x-ray, a complete metabolic panel ( contains a Creatinine), Complete blood count, immunosuppressant drug blood levels, and a heart biopsy (at the same intervals described above). ;


Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention


Related Conditions & MeSH terms


NCT number NCT01078363
Study type Interventional
Source Stanford University
Contact
Status Active, not recruiting
Phase N/A
Start date June 2009
Completion date April 2015

See also
  Status Clinical Trial Phase
Completed NCT02880137 - Real Time Myocardial Perfusion Echocardiography for Coronary Allograft Vasculopathy Phase 4
Terminated NCT01848301 - Endothelial Injury and Development of Coronary Intimal Thickening After Heart Transplantation Phase 1
Terminated NCT01278745 - Prevention of Cardiac Allograft Vasculopathy Using Rituximab (Rituxan) Therapy in Cardiac Transplantation Phase 2
Withdrawn NCT01812434 - Phosphodiesterase-5 (PDE-5) Inhibition in Heart Transplant Recipients N/A
Withdrawn NCT01305382 - Noninvasive Evaluation of Cardiac Allograft Vasculopathy N/A
Recruiting NCT05826444 - Microvascular Cardiac Allograft Vasculopathy Trial
Suspended NCT05756088 - Determining the Association of Microvascular Disease as Assessed by PET and Graft Injury by Donor Derived Cell Free DNA
Completed NCT02013037 - The De-novo Use of Eculizumab in Presensitized Patients Receiving Cardiac Transplantation Phase 3
Withdrawn NCT01157949 - A Study to Compare the Effectiveness of a Drug That Suppresses the Immune System Called Thymoglobulin® in Preventing the Development of a Disease That Affects the Majority of Heart Transplant Recipients Called Cardiac Allograft Vasculopathy (CAV) Phase 3
Withdrawn NCT01305395 - Strategies To Prevent Cardiac Allograft Vasculopathy Related Events in Heart Transplant Recipients N/A
Enrolling by invitation NCT06147271 - Impact of SGLT2 Inhibitors in Heart Transplant Recipients Phase 2
Recruiting NCT04193306 - Efficacy and Safety Of Alirocumab to Prevent Early Cardiac Allograft Vasculopathy in Recent Heart Transplant Recipients Phase 4
Recruiting NCT02798731 - Physiologic Assessment of Microvascular Function in Heart Transplant Patients
Withdrawn NCT02777255 - Severe CAV MRI in Heart Transplant Recipient N/A
Completed NCT05373108 - Endothelin-1 and Cardiac Allograft Vasculopathy (CAV) Phase 4
Withdrawn NCT01424917 - Noninvasive Predictors of Transplant Vasculopathy N/A
Recruiting NCT04770012 - AERIAL Trial: Antiplatelet Therapy in Heart Transplantation Phase 3
Completed NCT03734211 - Cholesterol Lowering With EVOLocumab to Prevent Cardiac Allograft Vasculopathy in De-novo Heart Transplant Recipients Phase 3
Recruiting NCT06089486 - MARINER Trial: Multiparametric Cardiac PET for CAV Surveillance After Heart Transplantation N/A
Active, not recruiting NCT03386539 - Tacrolimus/Everolimus vs. Tacrolimus/MMF in Pediatric Heart Transplant Recipients Using the MATE Score Phase 3