Prevention of Cardiac Allograft Vasculopathy Using Rituximab (Rituxan) Therapy in Cardiac Transplantation
- Conditions
- Cardiac Allograft VasculopathyHeart Transplant Recipients
- Interventions
- Biological: Rituximab induction/conventional immunosuppression (tacrolimus, MMF, and steroid taper)Drug: Rituximab placebo/conventional immunosuppression (tacrolimus, MMF, and steroid taper)
- Registration Number
- NCT01278745
- Brief Summary
All people who have a heart transplant are at risk for developing cardiac allograft vasculopathy (CAV). CAV means narrowing of the heart transplant vessels, which is associated with poor heart transplant function. People who develop antibodies after transplant have a higher risk of developing CAV. Infections, high cholesterol, and rejection also increase the risk of developing CAV. People who develop CAV usually have to receive another transplant.
- Detailed Description
The purpose of this research study is to see if a study drug called rituximab (Rituxan®) prevents CAV. Rituximab destroys certain types of white blood cells called B cells. B cells are important cells in the immune system that help the body fight infection by producing substances called antibodies. B cells and the antibodies they produce are also involved in some kinds of rejection after organ transplantation. Rituximab decreases the number of B cells in the blood and other tissues. The goal of this study is to determine if decreasing B cells with Rituximab can prevent injury to the transplanted heart.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 362
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Rituximab Rituximab induction/conventional immunosuppression (tacrolimus, MMF, and steroid taper) Rituximab induction/conventional immunosuppression Rituximab Placebo Rituximab placebo/conventional immunosuppression (tacrolimus, MMF, and steroid taper) Rituximab Placebo / conventional immunosuppression
- Primary Outcome Measures
Name Time Method Change in Percent Atheroma Volume (PAV) Baseline, 1 year Nominal or noticeable change, bad or good, from baseline to 1 year in percent atheroma volume (PAV) which is a measure of the degree of coronary arterial obstruction due to host alloimmune processes measured by intravascular ultrasound (IVUS) in a target coronary artery. Thus a decrease in PAV would be an indicator of less obstruction and a better outcome.
- Secondary Outcome Measures
Name Time Method Death 12 months Participants who died within 12 months post-transplant
Re-transplantation or Re-listed for Transplantation 6 to 12 months Re-transplantation is defined as the receipt of a subsequent heart transplant and re-listed for transplantation is being listed back on the heart transplant list to be re-transplanted.
Number of Episodes of Biopsy Proven Acute Rejection (BPAR) of Any Grade Per Participant 6 to 12 months The number of times a participant experienced biopsy proven acute rejection (BPAR). Biopsy proven acute rejection is when an examination of tissue removed from the transplanted organ indicates that the subject's immune system is trying to reject the graft. BPAR was defined as a biopsy that met the International Society for Heart \& Lung Transplantation (ISHLT) criteria to be graded as 1R or greater rejection and was determined by a single, central pathology laboratory.
Incidence of BPAR (Any Grade) 6 to 12 months The number of subjects who experienced any grade of biopsy proven acute rejection (BPAR) within the clinical trial. Biopsy proven acute rejection is when an examination of tissue removed from the transplanted organ indicates that the subject's immune system is trying to reject the graft. BPAR was defined as a biopsy which met The International Society for Heart \& Lung Transplantation (ISHLT) criteria to be graded as 1R or greater rejection and was determined by a single, central pathology laboratory.
Incidence of AMR 6 to 12 months The number of participants who experienced antibody- mediated rejection (AMR). Antibody-mediated rejection (AMR) occurs when the subject develops antibodies directed against the transplanted heart. This was assessed based on local pathology biopsy reads.
Incidence of Cellular Rejection 6 to 12 months Cellular Rejection refers to the organ recipient's immune system recognizing a transplanted organ as foreign and mounting a response to it via cellular mechanisms. Cellular rejection was defined as a biopsy which met The International Society for Heart \& Lung Transplantation (ISHLT) criteria to be graded as 1R or greater rejection and was determined by a single, central pathology laboratory
Incidence of Any Treated Rejection 6 to 12 months The number of participants who were treated by their local physician for any type of rejection including, but not limited to cellular rejection and antibody- mediated rejection (AMR) of the transplanted heart regardless of the presence of a biopsy.
Number of Participants With Episodes of Rejection Associated With Hemodynamic Compromise (HDC) 6 to 12 months The number of participants that experienced at least one episode of rejection associated with hemodynamic compromise (HDC). Rejection associated with HDC is when there is insufficient blood flow to the transplanted heart in association with acute rejection found in a biopsy. Local biopsies were used for this outcome measure.
Number of Participants With Development of Angiographically Evident Cardiac Allograft Vasculopathy 1 year Cardiac allograft vasculopathy is an aggressive form of atherosclerosis that is characterized by the development of fibrosis affecting cardiac arteries that result in concentric narrowing of the arteries and, ultimately allograft failure. Development of cardiac allograft vasculopathy can be diagnosed via an angiograph which is an X-ray of the cardiac arteries by injecting a radiopaque substance such as iodine.
Number of Participants With Post-transplant Serious Infections Requiring Intravenous Antimicrobial Therapy Transplantation through end of study, up to 1 year post transplantation. Number of participants experiencing at least one serious infection requiring intravenous antimicrobial therapy which is used to kill the growth of microorganisms such as bacteria, fungi, or protozoans.
Number of Participants With Post-transplant Incidence of PTLD Transplantation through end of study, up to 1 year post transplantation. The number of participants experiencing at least one post-transplant lymphoproliferative disorder (PTLD) occurrence during this trial. Post-transplant lymphoproliferative disorder is an uncontrolled proliferation of B cell lymphocytes latently infected with Epstein-Barr virus.
Post-transplant Safety Outcomes Among Participants: Safety and Tolerability of Rituximab Transplantation through end of study, up to 1 year post transplantation Defined as participants that experienced at least one adverse event that was possibly, probably, or definitely related to the study drug (i.e., Rituximab or Placebo). Serious adverse events were used to evaluate this endpoint and the attribution was based on the DAIT Medical Monitor's assessment.
Trial Locations
- Locations (24)
Ronald Regan UCLA Medical Center
🇺🇸Los Angeles, California, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
Drexel University College of Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Medical City Dallas Hospital/CRSTI
🇺🇸Dallas, Texas, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Intermountain Medical Center
🇺🇸Murray, Utah, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
Stanford University/Palo Alto VA
🇺🇸Palo Alto, California, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
The Methodist Hospital
🇺🇸Houston, Texas, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Cedars Sinai Heart Institute
🇺🇸Beverly Hills, California, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Minneapolis Heart Institute
🇺🇸Minneapolis, Minnesota, United States
Stanford University
🇺🇸Stanford, California, United States