Randall C Starling1, Brian Armstrong2, Nancy D Bridges3, Howard Eisen4, Michael M Givertz5, Abdallah G Kfoury6, Jon Kobashigawa7, David Ikle2, Yvonne Morrison3, Sean Pinney8, Josef Stehlik9, Sudipta Tripathi5, Mohamed H Sayegh5, Anil Chandraker10. 1. Department of Medicine, Cleveland Clinic Foundation, Cleveland, Ohio. Electronic address: https://twitter.com/rcstarling. 2. Rho Federal Systems Division, Chapel Hill, North Carolina. 3. National Institute of Allergy and Infectious Diseases, Bethesda, Maryland. 4. Department of Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania. 5. Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Boston, Massachusetts. 6. Department of Medicine, Intermountain Medical Center, Murray, Utah. 7. Department of Medicine, Cedars Sinai Medical Center, Los Angeles, California. 8. Department of Medicine, Mount Sinai School of Medicine, New York, New York. 9. Department of Medicine, University of Utah, Salt Lake City, Utah. 10. Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: achandraker@bwh.harvard.edu.
Abstract
BACKGROUND: The CTOT-11 (Prevention of Cardiac Allograft Vasculopathy Using Rituximab Therapy in Cardiac Transplantation [Clinical Trials in Organ Transplantation-11]) study was a randomized, placebo-controlled, multicenter, double-blinded clinical trial in nonsensitized primary heart transplant (HTX) recipients. OBJECTIVES: The study sought to determine whether B cell depletion therapy would attenuate the development of cardiac allograft vasculopathy. METHODS: A total of 163 HTX recipients were randomized to rituximab 1,000 mg intravenous or placebo on days 0 and 12 post-transplant. Primary outcome was change in percent atheroma volume (PAV) from baseline to 1 year measured by intravascular ultrasound. Secondary outcomes included treated episodes of acute rejection, de novo anti-HLA antibodies (including donor-specific antibodies), and phenotypic differentiation of B cells. RESULTS: There were no significant differences at study entry between the rituximab and placebo groups. Paired intravascular ultrasound measures were available at baseline and 1 year in 86 subjects (49 rituximab, 37 placebo). The mean ± SD change in PAV at 12 months was +6.8 ± 8.2% rituximab versus +1.9 ± 4.4% placebo (p = 0.0019). Mortality at 12 months was 3.4% rituximab versus 6.8% placebo (p = 0.47); there were no retransplants or post-transplant lymphoproliferative disorder. The rate of treated rejection was 24.7% rituximab versus 32.4% placebo (p = 0.28). Rituximab therapy effectively eliminated CD20+/CD19+ B cells followed by a gradual expansion of a CD19- cell population in the rituximab-treated group. CONCLUSIONS: A marked, unexpected increase in coronary artery PAV with rituximab was observed during the first year in HTX recipients. One-year mortality was not impacted; however, longer-term follow-up and mechanistic explanations are required. (Prevention of Cardiac Allograft Vasculopathy Using Rituximab [Rituxan] Therapy in Cardiac Transplantation; NCT01278745).
RCT Entities:
BACKGROUND: The CTOT-11 (Prevention of Cardiac Allograft Vasculopathy Using Rituximab Therapy in Cardiac Transplantation [Clinical Trials in Organ Transplantation-11]) study was a randomized, placebo-controlled, multicenter, double-blinded clinical trial in nonsensitized primary heart transplant (HTX) recipients. OBJECTIVES: The study sought to determine whether B cell depletion therapy would attenuate the development of cardiac allograft vasculopathy. METHODS: A total of 163 HTX recipients were randomized to rituximab 1,000 mg intravenous or placebo on days 0 and 12 post-transplant. Primary outcome was change in percent atheroma volume (PAV) from baseline to 1 year measured by intravascular ultrasound. Secondary outcomes included treated episodes of acute rejection, de novo anti-HLA antibodies (including donor-specific antibodies), and phenotypic differentiation of B cells. RESULTS: There were no significant differences at study entry between the rituximab and placebo groups. Paired intravascular ultrasound measures were available at baseline and 1 year in 86 subjects (49 rituximab, 37 placebo). The mean ± SD change in PAV at 12 months was +6.8 ± 8.2% rituximab versus +1.9 ± 4.4% placebo (p = 0.0019). Mortality at 12 months was 3.4% rituximab versus 6.8% placebo (p = 0.47); there were no retransplants or post-transplant lymphoproliferative disorder. The rate of treated rejection was 24.7% rituximab versus 32.4% placebo (p = 0.28). Rituximab therapy effectively eliminated CD20+/CD19+ B cells followed by a gradual expansion of a CD19- cell population in the rituximab-treated group. CONCLUSIONS: A marked, unexpected increase in coronary artery PAV with rituximab was observed during the first year in HTX recipients. One-year mortality was not impacted; however, longer-term follow-up and mechanistic explanations are required. (Prevention of Cardiac Allograft Vasculopathy Using Rituximab [Rituxan] Therapy in Cardiac Transplantation; NCT01278745).
Authors: Robin Schmitz; Zachary W Fitch; Paul M Schroder; Ashley Y Choi; Annette M Jackson; Stuart J Knechtle; Jean Kwun Journal: Transpl Int Date: 2020-01 Impact factor: 3.782
Authors: Carolina Moore; Baoshan Gao; Krishna M Roskin; Elena-Rodica M Vasilescu; Linda Addonizio; Michael M Givertz; Joren C Madsen; Emmanuel Zorn Journal: Am J Transplant Date: 2019-12-27 Impact factor: 8.086
Authors: Christina L Kaufman; Jean Kanitakis; Annemarie Weissenbacher; Gerald Brandacher; Mandeep R Mehra; Hatem Amer; Bettina G Zelger; Bernhard Zelger; Bohdan Pomahac; Sue McDiarmid; Linda Cendales; Emmanuel Morelon Journal: SAGE Open Med Date: 2020-07-14