BACKGROUND:Tacrolimus (formerly FK506) was first used clinically in 1989 to successfully replace cyclosporine in hepatic transplant recipients who were experiencing intractable rejection or as the baseline drug from the time of operation. After extensive pilot experience, an institutional review board-mandated clinical trial comparing cyclosporine with tacrolimus was performed. STUDY DESIGN:From February 16, 1990 to December 26, 1991, 154 patients were recruited. The competing drugs were combined with equal induction doses of prednisone in both arms of the study for the first 81 patients and with subsequently higher doses of prednisone in the remaining 35 patients who received cyclosporine and were entered into the trial. Drug crossover was permitted for lack of efficacy or adverse events. End points were rejection confirmed by biopsy and treatment failure leading to retransplantation or death. RESULTS:Seventy-nine patients were randomized to the tacrolimus arm and 75 to the cyclosporine arm during 1990 and 1991. All patients were available for follow-up throughout the trial, which terminated on May 30, 1995. The mean duration of follow-up was four years. Patients randomized to the tacrolimus arm were less likely to experience acute rejection than were those receiving cyclosporine, with 36.2 percent of the patients receiving tacrolimus and 16.8 percent of the patients receiving cyclosporine showing freedom from rejection at one year (p = 0.003, likelihood ratio test). Survival of patients over the course of the study was virtually the same in the two groups.
RCT Entities:
BACKGROUND:Tacrolimus (formerly FK506) was first used clinically in 1989 to successfully replace cyclosporine in hepatic transplant recipients who were experiencing intractable rejection or as the baseline drug from the time of operation. After extensive pilot experience, an institutional review board-mandated clinical trial comparing cyclosporine with tacrolimus was performed. STUDY DESIGN: From February 16, 1990 to December 26, 1991, 154 patients were recruited. The competing drugs were combined with equal induction doses of prednisone in both arms of the study for the first 81 patients and with subsequently higher doses of prednisone in the remaining 35 patients who received cyclosporine and were entered into the trial. Drug crossover was permitted for lack of efficacy or adverse events. End points were rejection confirmed by biopsy and treatment failure leading to retransplantation or death. RESULTS: Seventy-nine patients were randomized to the tacrolimus arm and 75 to the cyclosporine arm during 1990 and 1991. All patients were available for follow-up throughout the trial, which terminated on May 30, 1995. The mean duration of follow-up was four years. Patients randomized to the tacrolimus arm were less likely to experience acute rejection than were those receiving cyclosporine, with 36.2 percent of the patients receiving tacrolimus and 16.8 percent of the patients receiving cyclosporine showing freedom from rejection at one year (p = 0.003, likelihood ratio test). Survival of patients over the course of the study was virtually the same in the two groups.
Authors: K Tamura; M Kobayashi; K Hashimoto; K Kojima; K Nagase; K Iwasaki; T Kaizu; H Tanaka; M Niwa Journal: Transplant Proc Date: 1987-10 Impact factor: 1.066
Authors: R Y Calne; K Rolles; D J White; S Thiru; D B Evans; P McMaster; D C Dunn; G N Craddock; R G Henderson; S Aziz; P Lewis Journal: Lancet Date: 1979-11-17 Impact factor: 79.321
Authors: T E Starzl; J Fung; M Jordan; R Shapiro; A Tzakis; J McCauley; J Johnston; Y Iwaki; A Jain; M Alessiani Journal: JAMA Date: 1990-07-04 Impact factor: 56.272
Authors: T E Starzl; R Weil; S Iwatsuki; G Klintmalm; G P Schröter; L J Koep; Y Iwaki; P I Terasaki; K A Porter Journal: Surg Gynecol Obstet Date: 1980-07
Authors: K Abu-Elmagd; J Fung; J Reyes; A Rao; A Jain; G Mazariegos; W Marsh; J Madariaga; I Dvorchik; J Bueno; J Rogers; J McMichael; F Dodson; H Vargus; J Martin; A Slivka; V Balan; R Corry; J Rakela; N Murase; J Demetris; S Iwatsuki; T Starzl Journal: Clin Transpl Date: 1998
Authors: A C Tsamandas; S M Pham; E C Seaberg; O Pappo; R L Kormos; A Kawai; B P Griffith; A Zeevi; R Duquesnoy; J J Fung; T E Starzl; A J Demetris Journal: J Heart Lung Transplant Date: 1997-07 Impact factor: 10.247
Authors: A D Pinna; S Iwatsuki; R G Lee; S Todo; J R Madariaga; J W Marsh; A Casavilla; I Dvorchik; J J Fung; T E Starzl Journal: Hepatology Date: 1997-10 Impact factor: 17.425
Authors: A Jain; J Reyes; R Kashyap; S F Dodson; A J Demetris; K Ruppert; K Abu-Elmagd; W Marsh; J Madariaga; G Mazariegos; D Geller; C A Bonham; T Gayowski; T Cacciarelli; P Fontes; T E Starzl; J J Fung Journal: Ann Surg Date: 2000-10 Impact factor: 12.969