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

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00149994
First received: September 6, 2005
Last updated: April 7, 2011
Last verified: April 2011
  Purpose

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 Intervention Phase
Liver Transplant
Drug: Cyclosporine A
Drug: Tacrolimus
Drug: Basiliximab
Drug: Methylprednisolone
Drug: Prednisone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 171
Study Start Date: December 2002
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00149994

Locations
Switzerland
Novartis
Basel, Switzerland
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Novartis
  More Information

No publications provided

Responsible Party: External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00149994     History of Changes
Other Study ID Numbers: COLO400ANL07
Study First Received: September 6, 2005
Results First Received: January 25, 2011
Last Updated: April 7, 2011
Health Authority: Netherlands: Independent Ethics Committee

Keywords provided by Novartis:
Liver transplant, adults, C2 monitoring

Additional relevant MeSH terms:
Cyclosporins
Cyclosporine
Tacrolimus
Basiliximab
Methylprednisolone acetate
Prednisolone acetate
Prednisone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics

ClinicalTrials.gov processed this record on September 22, 2014