European randomised trial of dual versus triple tacrolimus-based regimens for control of acute rejection in renal allograft recipients

René W S Chang, Susan Snowden, Andrew Palmer, Jonathan T C Kwan, Michael Nicholson, S. Habib Kashi, Ossie N. Fernando, F. Perner, Guy H. Neild

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Two large multicentre studies have shown superiority of tacrolimus-based immunosuppressive regimens compared with standard cyclosporine-based therapy in renal transplantation. In these studies, tacrolimus was used in a triple drug regimen of tacrolimus, corticosteroids, and azathioprine. The present study aimed to determine whether a tacrolimus-based dual regimen achieves a similar efficacy and safety profile compared with conventional triple therapy. In this prospective, open, multicentre trial, 249 patients were randomised to receive either dual therapy (n = 125) of oral tacrolimus (initial daily dose of 0.2 mg/kg) and oral prednisone or additionally, as a triple therapy (n = 124), oral azathioprine. The primary endpoint was the incidence of acute rejection at month 3. In addition, all patients were included into a follow-up evaluation at 1 year after transplantation. Both treatment groups had similar baseline characteristics. At month 3, patient survival was 97.6 % (dual) and 96.7 % (triple); graft survival was 92.7 % (dual) and 91.7 % (triple). The incidence of treated acute rejection confirmed by biopsy was 27.4 % (dual) and 24.8 % (triple); difference 2.6 %, 95 % CI [-9.4 % -12.9 %], P = 0.755. The incidence of corticosteroid-resistant rejection (biopsy-confirmed) was 9.7 % (dual) and 10.7 % (triple). The overall adverse events profile was similar; leukopenia (1.6 % vs 11.6 %, P = 0.002) was more frequent with triple therapy. Between months 4 and 12, six (dual) and eight (triple) patients had a rejection. At month 12, patient survival was 95.6 % (dual) and 93.6 % (triple); graft survival was 91.8 % (dual) and 90.7 % (triple). Tacrolimus proved to be efficacious and safe with both dual and triple low-dose regimens. The addition of azathioprine to a tacrolimus/corticosteroid-based therapy did not result in an increased efficacy.

Original languageEnglish
Pages (from-to)384-390
Number of pages7
JournalTransplant International
Volume14
Issue number6
DOIs
Publication statusPublished - 2001

Fingerprint

Tacrolimus
Allografts
Kidney
Azathioprine
Adrenal Cortex Hormones
Graft Survival
Therapeutics
Multicenter Studies
Incidence
Biopsy
Survival
Leukopenia
Immunosuppressive Agents
Prednisone
Kidney Transplantation
Cyclosporine
Transplantation
Safety
Pharmaceutical Preparations

Keywords

  • Acute rejection
  • Immunosuppression
  • Kidney transplantation
  • Tacrolimus

ASJC Scopus subject areas

  • Transplantation

Cite this

Chang, R. W. S., Snowden, S., Palmer, A., Kwan, J. T. C., Nicholson, M., Kashi, S. H., ... Neild, G. H. (2001). European randomised trial of dual versus triple tacrolimus-based regimens for control of acute rejection in renal allograft recipients. Transplant International, 14(6), 384-390. https://doi.org/10.1007/s001470100003

European randomised trial of dual versus triple tacrolimus-based regimens for control of acute rejection in renal allograft recipients. / Chang, René W S; Snowden, Susan; Palmer, Andrew; Kwan, Jonathan T C; Nicholson, Michael; Kashi, S. Habib; Fernando, Ossie N.; Perner, F.; Neild, Guy H.

In: Transplant International, Vol. 14, No. 6, 2001, p. 384-390.

Research output: Contribution to journalArticle

Chang, René W S ; Snowden, Susan ; Palmer, Andrew ; Kwan, Jonathan T C ; Nicholson, Michael ; Kashi, S. Habib ; Fernando, Ossie N. ; Perner, F. ; Neild, Guy H. / European randomised trial of dual versus triple tacrolimus-based regimens for control of acute rejection in renal allograft recipients. In: Transplant International. 2001 ; Vol. 14, No. 6. pp. 384-390.
@article{e5a10554d3404361ab9e895221e168df,
title = "European randomised trial of dual versus triple tacrolimus-based regimens for control of acute rejection in renal allograft recipients",
abstract = "Two large multicentre studies have shown superiority of tacrolimus-based immunosuppressive regimens compared with standard cyclosporine-based therapy in renal transplantation. In these studies, tacrolimus was used in a triple drug regimen of tacrolimus, corticosteroids, and azathioprine. The present study aimed to determine whether a tacrolimus-based dual regimen achieves a similar efficacy and safety profile compared with conventional triple therapy. In this prospective, open, multicentre trial, 249 patients were randomised to receive either dual therapy (n = 125) of oral tacrolimus (initial daily dose of 0.2 mg/kg) and oral prednisone or additionally, as a triple therapy (n = 124), oral azathioprine. The primary endpoint was the incidence of acute rejection at month 3. In addition, all patients were included into a follow-up evaluation at 1 year after transplantation. Both treatment groups had similar baseline characteristics. At month 3, patient survival was 97.6 {\%} (dual) and 96.7 {\%} (triple); graft survival was 92.7 {\%} (dual) and 91.7 {\%} (triple). The incidence of treated acute rejection confirmed by biopsy was 27.4 {\%} (dual) and 24.8 {\%} (triple); difference 2.6 {\%}, 95 {\%} CI [-9.4 {\%} -12.9 {\%}], P = 0.755. The incidence of corticosteroid-resistant rejection (biopsy-confirmed) was 9.7 {\%} (dual) and 10.7 {\%} (triple). The overall adverse events profile was similar; leukopenia (1.6 {\%} vs 11.6 {\%}, P = 0.002) was more frequent with triple therapy. Between months 4 and 12, six (dual) and eight (triple) patients had a rejection. At month 12, patient survival was 95.6 {\%} (dual) and 93.6 {\%} (triple); graft survival was 91.8 {\%} (dual) and 90.7 {\%} (triple). Tacrolimus proved to be efficacious and safe with both dual and triple low-dose regimens. The addition of azathioprine to a tacrolimus/corticosteroid-based therapy did not result in an increased efficacy.",
keywords = "Acute rejection, Immunosuppression, Kidney transplantation, Tacrolimus",
author = "Chang, {Ren{\'e} W S} and Susan Snowden and Andrew Palmer and Kwan, {Jonathan T C} and Michael Nicholson and Kashi, {S. Habib} and Fernando, {Ossie N.} and F. Perner and Neild, {Guy H.}",
year = "2001",
doi = "10.1007/s001470100003",
language = "English",
volume = "14",
pages = "384--390",
journal = "Transplant International",
issn = "0934-0874",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - European randomised trial of dual versus triple tacrolimus-based regimens for control of acute rejection in renal allograft recipients

AU - Chang, René W S

AU - Snowden, Susan

AU - Palmer, Andrew

AU - Kwan, Jonathan T C

AU - Nicholson, Michael

AU - Kashi, S. Habib

AU - Fernando, Ossie N.

AU - Perner, F.

AU - Neild, Guy H.

PY - 2001

Y1 - 2001

N2 - Two large multicentre studies have shown superiority of tacrolimus-based immunosuppressive regimens compared with standard cyclosporine-based therapy in renal transplantation. In these studies, tacrolimus was used in a triple drug regimen of tacrolimus, corticosteroids, and azathioprine. The present study aimed to determine whether a tacrolimus-based dual regimen achieves a similar efficacy and safety profile compared with conventional triple therapy. In this prospective, open, multicentre trial, 249 patients were randomised to receive either dual therapy (n = 125) of oral tacrolimus (initial daily dose of 0.2 mg/kg) and oral prednisone or additionally, as a triple therapy (n = 124), oral azathioprine. The primary endpoint was the incidence of acute rejection at month 3. In addition, all patients were included into a follow-up evaluation at 1 year after transplantation. Both treatment groups had similar baseline characteristics. At month 3, patient survival was 97.6 % (dual) and 96.7 % (triple); graft survival was 92.7 % (dual) and 91.7 % (triple). The incidence of treated acute rejection confirmed by biopsy was 27.4 % (dual) and 24.8 % (triple); difference 2.6 %, 95 % CI [-9.4 % -12.9 %], P = 0.755. The incidence of corticosteroid-resistant rejection (biopsy-confirmed) was 9.7 % (dual) and 10.7 % (triple). The overall adverse events profile was similar; leukopenia (1.6 % vs 11.6 %, P = 0.002) was more frequent with triple therapy. Between months 4 and 12, six (dual) and eight (triple) patients had a rejection. At month 12, patient survival was 95.6 % (dual) and 93.6 % (triple); graft survival was 91.8 % (dual) and 90.7 % (triple). Tacrolimus proved to be efficacious and safe with both dual and triple low-dose regimens. The addition of azathioprine to a tacrolimus/corticosteroid-based therapy did not result in an increased efficacy.

AB - Two large multicentre studies have shown superiority of tacrolimus-based immunosuppressive regimens compared with standard cyclosporine-based therapy in renal transplantation. In these studies, tacrolimus was used in a triple drug regimen of tacrolimus, corticosteroids, and azathioprine. The present study aimed to determine whether a tacrolimus-based dual regimen achieves a similar efficacy and safety profile compared with conventional triple therapy. In this prospective, open, multicentre trial, 249 patients were randomised to receive either dual therapy (n = 125) of oral tacrolimus (initial daily dose of 0.2 mg/kg) and oral prednisone or additionally, as a triple therapy (n = 124), oral azathioprine. The primary endpoint was the incidence of acute rejection at month 3. In addition, all patients were included into a follow-up evaluation at 1 year after transplantation. Both treatment groups had similar baseline characteristics. At month 3, patient survival was 97.6 % (dual) and 96.7 % (triple); graft survival was 92.7 % (dual) and 91.7 % (triple). The incidence of treated acute rejection confirmed by biopsy was 27.4 % (dual) and 24.8 % (triple); difference 2.6 %, 95 % CI [-9.4 % -12.9 %], P = 0.755. The incidence of corticosteroid-resistant rejection (biopsy-confirmed) was 9.7 % (dual) and 10.7 % (triple). The overall adverse events profile was similar; leukopenia (1.6 % vs 11.6 %, P = 0.002) was more frequent with triple therapy. Between months 4 and 12, six (dual) and eight (triple) patients had a rejection. At month 12, patient survival was 95.6 % (dual) and 93.6 % (triple); graft survival was 91.8 % (dual) and 90.7 % (triple). Tacrolimus proved to be efficacious and safe with both dual and triple low-dose regimens. The addition of azathioprine to a tacrolimus/corticosteroid-based therapy did not result in an increased efficacy.

KW - Acute rejection

KW - Immunosuppression

KW - Kidney transplantation

KW - Tacrolimus

UR - http://www.scopus.com/inward/record.url?scp=0035665112&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035665112&partnerID=8YFLogxK

U2 - 10.1007/s001470100003

DO - 10.1007/s001470100003

M3 - Article

C2 - 11793035

AN - SCOPUS:0035665112

VL - 14

SP - 384

EP - 390

JO - Transplant International

JF - Transplant International

SN - 0934-0874

IS - 6

ER -