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

NCT ID: NCT00149994

Last Updated: 2011-04-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 171 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-12-31
• Study Completion Date: 2007-12-31

Brief Summary

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.

Conditions

Liver Transplant

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Cyclosporine A

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.

Group Type: EXPERIMENTAL

Cyclosporine A

Intervention Type: DRUG

Basiliximab

Intervention Type: DRUG

Each patient was given two 20mg doses of Basiliximab as intravenous bolus injection at Day 0 and Day 4 post-transplant surgery.

Methylprednisolone

Intervention Type: DRUG

Methylprednisolone was given as an intravenous bolus of 500mg during transplant surgery

Prednisone

Intervention Type: DRUG

Post-operatively prednisone was tapered from an initial dose of 20mg/day to zero at 3 months or continued at 5-10mg if the indication for Orthotopic Liver Transplantation (OLTx) was of auto-immune nature.

Tacrolimus

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.

Group Type: ACTIVE_COMPARATOR

Tacrolimus

Intervention Type: DRUG

Basiliximab

Intervention Type: DRUG

Each patient was given two 20mg doses of Basiliximab as intravenous bolus injection at Day 0 and Day 4 post-transplant surgery.

Methylprednisolone

Intervention Type: DRUG

Methylprednisolone was given as an intravenous bolus of 500mg during transplant surgery

Prednisone

Intervention Type: DRUG

Post-operatively prednisone was tapered from an initial dose of 20mg/day to zero at 3 months or continued at 5-10mg if the indication for Orthotopic Liver Transplantation (OLTx) was of auto-immune nature.

Interventions

Cyclosporine A

Intervention Type: DRUG

Tacrolimus

Intervention Type: DRUG

Basiliximab

Each patient was given two 20mg doses of Basiliximab as intravenous bolus injection at Day 0 and Day 4 post-transplant surgery.

Intervention Type: DRUG

Methylprednisolone

Methylprednisolone was given as an intravenous bolus of 500mg during transplant surgery

Intervention Type: DRUG

Prednisone

Post-operatively prednisone was tapered from an initial dose of 20mg/day to zero at 3 months or continued at 5-10mg if the indication for Orthotopic Liver Transplantation (OLTx) was of auto-immune nature.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Novartis Pharmaceuticals

Principal Investigators

Novartis

Role: STUDY_DIRECTOR

Novartis

Locations

Novartis

Basel, , Switzerland

Countries

Switzerland

Other Identifiers

COLO400ANL07

Identifier Type: -

Identifier Source: org_study_id