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

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ClinicalTrials.gov Identifier: NCT00149994

Recruitment Status : Completed

First Posted : September 8, 2005

Results First Posted : February 14, 2011

Last Update Posted : April 12, 2011

Sponsor:

Information provided by:

Novartis

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Liver Transplant	Drug: Cyclosporine A Drug: Tacrolimus Drug: Basiliximab Drug: Methylprednisolone Drug: Prednisone	Phase 4

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	171 participants
Allocation:	Randomized
Intervention Model:	Factorial Assignment
Masking:	None (Open Label)
Primary Purpose:	Prevention
Official Title:	DELTA Study Dutch Evaluation in Liver Transplantation To Assess the Efficacy of Cyclosporine A Microemulsion With C-2h Monitoring Versus Tacrolimus With Trough Monitoring in de Novo Liver Transplant Recipients
Study Start Date :	December 2002
Actual Primary Completion Date :	December 2007
Actual Study Completion Date :	December 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Transplantation

Drug Information available for: Cyclosporine Tacrolimus

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: Cyclosporine A Drug: Basiliximab Each patient was given two 20mg doses of Basiliximab as intravenous bolus injection at Day 0 and Day 4 post-transplant surgery. Drug: Methylprednisolone Methylprednisolone was given as an intravenous bolus of 500mg during transplant surgery 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.
Active Comparator: 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.	Drug: Tacrolimus Drug: Basiliximab Each patient was given two 20mg doses of Basiliximab as intravenous bolus injection at Day 0 and Day 4 post-transplant surgery. Drug: Methylprednisolone Methylprednisolone was given as an intravenous bolus of 500mg during transplant surgery 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.

Arm

Intervention/treatment

Experimental: 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.

Drug: Cyclosporine A
Drug: Basiliximab

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

Drug: Methylprednisolone

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

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.

Active Comparator: 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.

Drug: Tacrolimus
Drug: Basiliximab

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

Drug: Methylprednisolone

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

Drug: Prednisone

Outcome Measures

Primary Outcome Measures :

Percentage of Participants With an Occurrence of Biopsy Proven Acute Rejection (BPAR) During the First 3 Months Post de Novo Liver Transplantation. [ Time Frame: Month 3 ]
A BPAR is defined when the investigator had a suspicion of an acute rejection, where the final clinical diagnosis confirmed the occurrence of an acute rejection, where a biopsy was performed that confirmed the presence of an acute rejection, and where anti-rejection treatment intervention was initiated. The efficacy measured the first rejections (clinically and biopsy proven rejections) at 3 months.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Older Adult)
Sexes Eligible for Study:	All

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.

Other protocol-defined exclusion criteria applied

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00149994

Locations

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Switzerland
Novartis
Basel, Switzerland

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

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Study Director:	Novartis	Novartis

More Information

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Responsible Party:	External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00149994
Other Study ID Numbers:	COLO400ANL07
First Posted:	September 8, 2005 Key Record Dates
Results First Posted:	February 14, 2011
Last Update Posted:	April 12, 2011
Last Verified:	April 2011

Keywords provided by Novartis:


Liver transplant, adults, C2 monitoring

Additional relevant MeSH terms:

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Cyclosporine Prednisone Methylprednisolone Tacrolimus Cyclosporins Basiliximab Anti-Inflammatory Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antineoplastic Agents, Hormonal Antineoplastic Agents Immunosuppressive Agents	Immunologic Factors Calcineurin Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antifungal Agents Anti-Infective Agents Dermatologic Agents Antirheumatic Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Gastrointestinal Agents Neuroprotective Agents Protective Agents

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