Cyclosporine A C-2h Monitoring Versus Tacrolimus C-0h Monitoring in de Novo Liver Transplant Recipients

Novartis

Status and phase: Completed; Phase 4

Conditions: Liver Transplant

Treatments: Drug: Prednisone; Drug: Methylprednisolone; Drug: Cyclosporine A; Drug: Tacrolimus; Drug: Basiliximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT00149994

COLO400ANL07

Details and patient eligibility

About

The purpose of this study is to determine whether cyclosporine A (in a micro emulsion formulation) monitored by sample taken 2 hour after oral dose (C-2h) will show equivalent or superior efficacy compared to tacrolimus monitored by pre-dose blood concentration (C-0h). In addition this study will assess the safety and tolerability of a cyclosporine A regimen based on C-2h monitoring in comparison to the standard tacrolimus regimen.

Enrollment: 171 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• About to undergo a primary liver transplant (including living donor, non-heart beating donor and split liver).
• Age between 18 and 75 years.
• Expected to be able to receive the first oral dose of CNI within the first 24 hours post-transplantation (Tx)

Exclusion criteria

• This is a multi-organ transplant or if the patient has previously been transplanted with any other organ.
• Urine production is <200 ml within 12 hours after reperfusion of the graft
• Severe coexisting disease is present or if any unstable medical condition is present which could affect the study objectives.

Other protocol-defined exclusion criteria applied

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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171 participants in 2 patient groups

Cyclosporine A

Experimental group

Description:

Cyclosporine A was given in a twice-daily schedule at 12-hour intervals. It was administered within the first 4 hours post-operatively (study day 1), at an initial dose of 10-15mg/kg/day in two doses, as close as possible to 15mg/kg/day. After the first oral administration, the dose of Cyclosporine A was adjusted to bring the sample taken 2 hours after oral dose (C-2h) level into the target range by Days 3-5 post-transplantation. C-2h target ranges post-transplantation: 0-3 months: range of 800-1200 ng/ml with midpoint of 1000 ng/ml; 4-6 months: range of 700-900 ng/ml with midpoint of 800 ng/ml; \> 6 months: range of 500-700 ng/ml with midpoint of 600 ng/ml is recommended. During the course of the study, the dose of Cyclosporine A was adjusted as necessary to achieve and maintain the C-2h blood Cyclosporine A (CsA) concentrations within the target ranges.

Treatment:

Drug: Methylprednisolone

Drug: Basiliximab

Drug: Cyclosporine A

Drug: Prednisone

Tacrolimus

Active Comparator group

Description:

Tacrolimus was given on a twice-daily schedule at 12-hour intervals which had to be maintained throughout the study period. Tacrolimus was administered within the first 24 hrs postoperatively (Study Day 1) at an initial dose of 0.1-0.15 mg/kg/day in two divided oral doses either by mouth or via an enteral feeding tube until the patient can swallow. The initial dosing level was determined by the patient's overall post-operative condition. During the course of the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain the pre-dose blood concentration (C-0h) (trough) tacrolimus concentrations. C-0h target ranges post-transplantation: 0-3 months: 10-15 ng/ml; 4-6 months: 5-10 ng/ml; \> 6 months: range of 5-10 ng/ml is recommended.

Treatment:

Drug: Tacrolimus

Drug: Methylprednisolone

Drug: Basiliximab

Drug: Prednisone