Efficacy and Safety of Concentration-controlled Everolimus to Eliminate or to Reduce Tacrolimus Compared to Tacrolimus in de Novo Liver Transplant Recipients

PHASE3CompletedINTERVENTIONAL
Enrollment

719

Participants

Timeline

Start Date

January 31, 2008

Primary Completion Date

April 30, 2012

Study Completion Date

April 30, 2012

Conditions
Liver Transplantation
Interventions
DRUG

Tacrolimus (reduced tacrolimus)

After everolimus whole blood trough levels were confirmed to be in the target range of 3-8 ng/mL, tacrolimus tapering began, achieving a target tacrolimus whole blood trough level of 3-5 ng/mL by 3 weeks after randomization, a level which was maintained for the duration of the study.

DRUG

Tacrolimus (tacrolimus elimination)

After everolimus whole blood trough levels were confirmed to be in the target range of 3-8 ng/mL, tacrolimus tapering began, achieving a target tacrolimus whole blood trough level of 3-5 ng/mL by 3 weeks after randomization. Tacrolimus elimination was started beginning at Month 4. Tacrolimus was tapered after everolimus whole blood trough levels were within the target range of 6-10 ng/mL. Tacrolimus was completely eliminated by the end of Month 4.

DRUG

Tacrolimus (tacrolimus control)

Tacrolimus trough levels were targeted to be maintained at 8-12 ng/mL until Month 4. At Month 4, tacrolimus whole blood trough levels were decreased to a target trough level of 6-10 ng/mL for the remainder of the study.

DRUG

Everolimus (reduced tacrolimus)

Everolimus was started within 24 hours of randomization at a dose of 1.0 mg twice a day (bid, 2 mg daily dose). The dose was adjusted to maintain everolimus trough blood levels between 3-8 ng/mL for the duration of the study.

DRUG

Everolimus (tacrolimus elimination)

Everolimus was started within 24 hours of randomization at a dose of 1.0 mg twice a day (bid, 2 mg daily dose). The dose was adjusted to maintain everolimus trough blood levels between 3-8 ng/mL until Month 4; beginning with Month 4, the dose was adjusted to maintain everolimus trough blood levels between 6-10 ng/mL.

DRUG

Corticosteroids

For patients in all groups, corticosteroids were initiated at or prior to the time of transplantation according to local practice. Corticosteroids could be used for the duration of the study but could not be eliminated before Month 6.

Trial Locations (91)

1082

Novartis Investigative Site, Budapest

2050

Novartis Investigative Site, Camperdown

3000

Novartis Investigative Site, Leuven

3084

Novartis Investigative Site, Heidelberg

4000

Novartis Investigative Site, Liège

5042

Novartis Investigative Site, Bedford Park

6009

Novartis Investigative Site, Nedlands

9000

Novartis Investigative Site, Ghent

10016

Novartis Investigative Site, New York

10032

Novartis Investigative Site, New York

10126

Novartis Investigative Site, Torino

13353

Novartis Investigative Site, Berlin

13385

Novartis Investigative Site, Marseille

19107

Novartis Investigative Site, Philadelphia

20162

Novartis Investigative Site, Milan

20246

Novartis Investigative Site, Hamburg

27599

Novartis Investigative Site, Chapel Hill

27710

Novartis Investigative Site, Durham

28007

Novartis Investigative Site, Madrid

28222

Novartis Investigative Site, Majadanonda

29425

Novartis Investigative Site, Charleston

30309

Novartis Investigative Site, Atlanta

31002

Novartis Investigative Site, Pamplona

33076

Novartis Investigative Site, Bordeaux

33606

Novartis Investigative Site, Tampa

34295

Novartis Investigative Site, Montpellier

37232

Novartis Investigative Site, Nashville

41100

Novartis Investigative Site, Modena

44195

Novartis Investigative Site, Cleveland

45147

Novartis Investigative Site, Essen

46026

Novartis Investigative Site, Valencia

48903

Novartis Investigative Site, Barakaldo

55131

Novartis Investigative Site, Mainz

55905

Novartis Investigative Site, Rochester

56124

Novartis Investigative Site, Pisa

59000

Novartis Investigative Site, Lille

60637

Novartis Investigative Site, Chicago

63110

Novartis Investigative Site, St Louis

64239

Novartis Investigative Site, Tel Aviv

69120

Novartis Investigative Site, Heidelberg

73112

Novartis Investigative Site, Oklahoma City

75246

Novartis Investigative Site, Dallas

77030

Novartis Investigative Site, Houston

80045

Novartis Investigative Site, Aurora

90033

Novartis Investigative Site, Los Angeles

90048

Novartis Investigative Site, Los Angeles

90095

Novartis Investigative Site, Los Angeles

91120

Novartis Investigative Site, Jerusalem

92110

Novartis Investigative Site, Clichy

93053

Novartis Investigative Site, Regensburg

94010

Novartis Investigative Site, Créteil

94143

Novartis Investigative Site, San Francisco

94805

Novartis Investigative Site, Villejuif

123182

Novartis Investigative Site, Moscow

129010

Novartis Investigative Site, Moscow

20007-2197

Novartis Investigative Site, Washington D.C.

40536-0293

Novartis Investigative Site, Lexington

48202-2689

Novartis Investigative Site, Detroit

07101

Novartis Investigative Site, Newark

97201-3098

Novartis Investigative Site, Portland

75208-2312

Novartis Investigative Site, Dallas

77030-2400

Novartis Investigative Site, Houston

C1118AAT

Novartis Investigative Site, Buenos Aires

C1181ACH

Novartis Investigative Site, Buenos Aires

W3400ABH

Novartis Investigative Site, Buenos Aires

C1107BEA

Novartis Investigative Site, San Martín

C2000DSR

Novartis Investigative Site, Rosario

21041-030

Novartis Investigative Site, Rio de Janeiro

90020-090

Novartis Investigative Site, Porto Alegre

89010-500

Novartis Investigative Site, Blumenau

14048-900

Novartis Investigative Site, Ribeirão Preto

01323-900

Novartis Investigative Site, São Paulo

T6G 2B7

Novartis Investigative Site, Edmonton

V5Z 1M9

Novartis Investigative Site, Vancouver

N6A 5A5

Novartis Investigative Site, London

M5G 2C4

Novartis Investigative Site, Toronto

Unknown

Novartis Investigative Site, Bogotá

Novartis Investigative Site, Medellín

Novartis Investigative Site, Santiago de Cali

Novartis Investigative Site, Dublin

140 21

Novartis Investigative Site, Prague

07740

Novartis Investigative Site, Jena

04103

Novartis Investigative Site, Leipzig

00161

Novartis Investigative Site, Roma

3015 CE

Novartis Investigative Site, Rotterdam

08035

Novartis Investigative Site, Barcelona

08036

Novartis Investigative Site, Barcelona

08907

Novartis Investigative Site, L'Hospitalet de Llobregat

141 86

Novartis Investigative Site, Stockholm

ED16 4SA

Novartis Investigative Site, Edinburgh

SE5 9RS

Novartis Investigative Site, London

Sponsors
All Listed Sponsors
lead

Novartis Pharmaceuticals

INDUSTRY