A prospective randomized multicenter study of tacrolimus in combination with sirolimus in renal-transplant recipients.
BACKGROUND
Recently, sirolimus (SRL) was introduced as an immunosuppressant in solid-organ transplantation. This study evaluated combinations of SRL and tacrolimus (Tac).


METHODS
This 6-month study investigated the safety and efficacy of Tac and steroids in combination with three different doses of SRL in renal-transplant recipients. A total of 104 patients were randomized in four groups: one group received Tac and steroids (control n=28), and three groups also received the following daily SRL doses: 0.5 mg (TacSRL0.5, n=25), 1 mg (TacSRL1, n=25), or 2 mg (TacSRL2, n=26). Tac doses were adjusted to whole-blood trough levels. Steroids were tapered from 20 mg per day to 5 mg per day. The SRL groups underwent a second randomization to discontinue SRL at either month 3 or 5.


RESULTS
At month 6, patient survival rates were 100%, 100%, 96.0%, and 100%, and graft survival rates were 96.4%, 84.0%, 88.0%, and 84.6%, respectively. The overall safety profile was similar in all groups. The incidences of infections during months 1 to 3 were similar in all groups (control 46.4%, TacSRL0.5 32.0%, TacSRL1 56.0%, TacSRL2 46.2%). The 3-month incidences of hypercholesteremia (cholesterol >240 mg/dL or low-density lipoprotein cholesterol >160 mg/dL) were 21.4%, 36.0%, 48.0%, and 50.0% (P=0.019). Lipid levels improved after withdrawal of SRL. The 3-month incidences of biopsy-proven acute rejection were 28.6% (control), 8.0% (TacSRL0.5), 8.0% (TacSRL1), and 3.8% (TacSRL2) (P=0.014).


CONCLUSIONS
Tac in combination with low doses of SRL provides a very effective and safe regimen.
van Hooff
Johannes P
JP
Academisch Ziekenhuis Maastricht, Department of Internal Medicine, Maastricht, The Netherlands. jho@sint.azm.nl
Squifflet
Jean-Paul
JP
Wlodarczyk
Zbigniew
Z
Vanrenterghem
Yves
Y
Paczek
Leszek
L
D000328:Adult; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D044469:Racial Groups; D020123:Sirolimus / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016559:Tacrolimus / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013997:Time Factors; D014019:Tissue Donors / Q000706:statistics & numerical data
D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus