A prospective randomized trial of tacrolimus and prednisone versus tacrolimus, prednisone, and mycophenolate mofetil in primary adult liver transplant recipients

An interim report

A. B. Jain, I. Hamad, Jorge Rakela, F. Dodson, D. Kramer, J. Demetris, J. Mcmichael, T. E. Starzl, J. J. Fung

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Background. Tacrolimus (Tac) and mycophenolate mofetil (MMF) are newly approved immunosuppressive agents. However, the safety and efficacy of the combination of MMF and Tac in primary liver transplantation has not been determined. Methods. An Institutional Review Board-approved, open-label prospective randomized protocol was initiated to study the efficacy and toxicity of Tac and steroids (double-drug therapy) versus Tac, steroids, and MMF (triple-drug therapy) in primary adult liver transplant recipients. Both groups of patients began on the same doses of Tac and steroids. Patients randomized to triple-drug therapy also received 1 g of MMF twice a day. Results. Between August 1995 and January 1997, 200 patients were enrolled, 99 in double-drug therapy and 101 in triple-drug therapy. All patients were followed until May 1997, with a mean follow-up of 12.7 months. During the study period, 28 of 99 patients in double-drug therapy received MMF to control ongoing acute rejection, nephrotoxicity, and/or neurotoxicity. On the other hand, 61 patients in triple-drug therapy discontinued MMF for infection, myelosuppression, and/or gastrointestinal disturbances. By an 'intention-to-treat analysis,' the actuarial 1-year patient survival rate was 85.1% in double-drug therapy and 83.1% in triple-drug therapy (P=0.77). The actuarial 1-year graft survival rate was 80.2% for double-drug therapy and 79.2% for triple-drug therapy (P=0.77). Forty-one patients (41.4%) in double- drug therapy and 32 (31.7%) in triple-drug therapy had at least one episode of rejection, but this was not statistically significant (P=0.15). The mean maintenance dose of corticosteroids was slightly lower in triple-drug compared with double-drug therapy. Conclusion. Patient and graft survival rates were similar in both groups. There was a trend to a lower incidence of rejection, reduced nephrotoxicity, and a lesser amount of maintenance corticosteroids in triple-drug therapy compared with double-drug therapy.

Original languageEnglish (US)
Pages (from-to)1395-1398
Number of pages4
JournalTransplantation
Volume66
Issue number10
StatePublished - Nov 27 1998
Externally publishedYes

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Mycophenolic Acid
Tacrolimus
Prednisone
Drug Therapy
Liver
Survival Rate
Transplant Recipients
Steroids
Graft Survival
Adrenal Cortex Hormones
Intention to Treat Analysis
Research Ethics Committees

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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A prospective randomized trial of tacrolimus and prednisone versus tacrolimus, prednisone, and mycophenolate mofetil in primary adult liver transplant recipients : An interim report. / Jain, A. B.; Hamad, I.; Rakela, Jorge; Dodson, F.; Kramer, D.; Demetris, J.; Mcmichael, J.; Starzl, T. E.; Fung, J. J.

In: Transplantation, Vol. 66, No. 10, 27.11.1998, p. 1395-1398.

Research output: Contribution to journalArticle

Jain, A. B. ; Hamad, I. ; Rakela, Jorge ; Dodson, F. ; Kramer, D. ; Demetris, J. ; Mcmichael, J. ; Starzl, T. E. ; Fung, J. J. / A prospective randomized trial of tacrolimus and prednisone versus tacrolimus, prednisone, and mycophenolate mofetil in primary adult liver transplant recipients : An interim report. In: Transplantation. 1998 ; Vol. 66, No. 10. pp. 1395-1398.
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abstract = "Background. Tacrolimus (Tac) and mycophenolate mofetil (MMF) are newly approved immunosuppressive agents. However, the safety and efficacy of the combination of MMF and Tac in primary liver transplantation has not been determined. Methods. An Institutional Review Board-approved, open-label prospective randomized protocol was initiated to study the efficacy and toxicity of Tac and steroids (double-drug therapy) versus Tac, steroids, and MMF (triple-drug therapy) in primary adult liver transplant recipients. Both groups of patients began on the same doses of Tac and steroids. Patients randomized to triple-drug therapy also received 1 g of MMF twice a day. Results. Between August 1995 and January 1997, 200 patients were enrolled, 99 in double-drug therapy and 101 in triple-drug therapy. All patients were followed until May 1997, with a mean follow-up of 12.7 months. During the study period, 28 of 99 patients in double-drug therapy received MMF to control ongoing acute rejection, nephrotoxicity, and/or neurotoxicity. On the other hand, 61 patients in triple-drug therapy discontinued MMF for infection, myelosuppression, and/or gastrointestinal disturbances. By an 'intention-to-treat analysis,' the actuarial 1-year patient survival rate was 85.1{\%} in double-drug therapy and 83.1{\%} in triple-drug therapy (P=0.77). The actuarial 1-year graft survival rate was 80.2{\%} for double-drug therapy and 79.2{\%} for triple-drug therapy (P=0.77). Forty-one patients (41.4{\%}) in double- drug therapy and 32 (31.7{\%}) in triple-drug therapy had at least one episode of rejection, but this was not statistically significant (P=0.15). The mean maintenance dose of corticosteroids was slightly lower in triple-drug compared with double-drug therapy. Conclusion. Patient and graft survival rates were similar in both groups. There was a trend to a lower incidence of rejection, reduced nephrotoxicity, and a lesser amount of maintenance corticosteroids in triple-drug therapy compared with double-drug therapy.",
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T1 - A prospective randomized trial of tacrolimus and prednisone versus tacrolimus, prednisone, and mycophenolate mofetil in primary adult liver transplant recipients

T2 - An interim report

AU - Jain, A. B.

AU - Hamad, I.

AU - Rakela, Jorge

AU - Dodson, F.

AU - Kramer, D.

AU - Demetris, J.

AU - Mcmichael, J.

AU - Starzl, T. E.

AU - Fung, J. J.

PY - 1998/11/27

Y1 - 1998/11/27

N2 - Background. Tacrolimus (Tac) and mycophenolate mofetil (MMF) are newly approved immunosuppressive agents. However, the safety and efficacy of the combination of MMF and Tac in primary liver transplantation has not been determined. Methods. An Institutional Review Board-approved, open-label prospective randomized protocol was initiated to study the efficacy and toxicity of Tac and steroids (double-drug therapy) versus Tac, steroids, and MMF (triple-drug therapy) in primary adult liver transplant recipients. Both groups of patients began on the same doses of Tac and steroids. Patients randomized to triple-drug therapy also received 1 g of MMF twice a day. Results. Between August 1995 and January 1997, 200 patients were enrolled, 99 in double-drug therapy and 101 in triple-drug therapy. All patients were followed until May 1997, with a mean follow-up of 12.7 months. During the study period, 28 of 99 patients in double-drug therapy received MMF to control ongoing acute rejection, nephrotoxicity, and/or neurotoxicity. On the other hand, 61 patients in triple-drug therapy discontinued MMF for infection, myelosuppression, and/or gastrointestinal disturbances. By an 'intention-to-treat analysis,' the actuarial 1-year patient survival rate was 85.1% in double-drug therapy and 83.1% in triple-drug therapy (P=0.77). The actuarial 1-year graft survival rate was 80.2% for double-drug therapy and 79.2% for triple-drug therapy (P=0.77). Forty-one patients (41.4%) in double- drug therapy and 32 (31.7%) in triple-drug therapy had at least one episode of rejection, but this was not statistically significant (P=0.15). The mean maintenance dose of corticosteroids was slightly lower in triple-drug compared with double-drug therapy. Conclusion. Patient and graft survival rates were similar in both groups. There was a trend to a lower incidence of rejection, reduced nephrotoxicity, and a lesser amount of maintenance corticosteroids in triple-drug therapy compared with double-drug therapy.

AB - Background. Tacrolimus (Tac) and mycophenolate mofetil (MMF) are newly approved immunosuppressive agents. However, the safety and efficacy of the combination of MMF and Tac in primary liver transplantation has not been determined. Methods. An Institutional Review Board-approved, open-label prospective randomized protocol was initiated to study the efficacy and toxicity of Tac and steroids (double-drug therapy) versus Tac, steroids, and MMF (triple-drug therapy) in primary adult liver transplant recipients. Both groups of patients began on the same doses of Tac and steroids. Patients randomized to triple-drug therapy also received 1 g of MMF twice a day. Results. Between August 1995 and January 1997, 200 patients were enrolled, 99 in double-drug therapy and 101 in triple-drug therapy. All patients were followed until May 1997, with a mean follow-up of 12.7 months. During the study period, 28 of 99 patients in double-drug therapy received MMF to control ongoing acute rejection, nephrotoxicity, and/or neurotoxicity. On the other hand, 61 patients in triple-drug therapy discontinued MMF for infection, myelosuppression, and/or gastrointestinal disturbances. By an 'intention-to-treat analysis,' the actuarial 1-year patient survival rate was 85.1% in double-drug therapy and 83.1% in triple-drug therapy (P=0.77). The actuarial 1-year graft survival rate was 80.2% for double-drug therapy and 79.2% for triple-drug therapy (P=0.77). Forty-one patients (41.4%) in double- drug therapy and 32 (31.7%) in triple-drug therapy had at least one episode of rejection, but this was not statistically significant (P=0.15). The mean maintenance dose of corticosteroids was slightly lower in triple-drug compared with double-drug therapy. Conclusion. Patient and graft survival rates were similar in both groups. There was a trend to a lower incidence of rejection, reduced nephrotoxicity, and a lesser amount of maintenance corticosteroids in triple-drug therapy compared with double-drug therapy.

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