Liver Fibrosis in Patients Transplanted for Hepatitis C Receiving Either Cyclosporine Microemulsion or Tacrolimus

This study has been terminated.

(Study was prematurely terminated due to poor recruitment.)

Sponsor:

Information provided by (Responsible Party):

Novartis ( Novartis Pharmaceuticals )

ClinicalTrials.gov Identifier:

NCT00260208

First received: November 30, 2005

Last updated: December 2, 2011

Last verified: December 2011

History of Changes

Results First Received: September 14, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Prevention
Conditions:	Liver Transplant Hepatitis C
Interventions:	Drug: Cyclosporine A Drug: Tacrolimus

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
361 patients were randomized, 185 to the cyclosporin A arm and 176 to tacrolimus. Five patients (1 cyclosporine A, 4 tacrolimus) did not receive any dose of study medication and were therefore excluded from the safety population.

Reporting Groups

Description

Cyclosporin A

The first administration of Cyclosporin A (CsA) was within the first 24 hours post-transplantation at an initial dose of 10-15mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally, via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the study, it was recommended that the dose of CsA was adjusted, as necessary, to achieve and maintain the C2 or C0 blood CsA concentration within the target ranges.

Tacrolimus

Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally or via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the course of the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain the C0 tacrolimus concentrations within target ranges.

Participant Flow: Overall Study

	Cyclosporin A	Tacrolimus
STARTED	184 ^[1]	172
Intent to Treat (ITT) Population	182	169
Modified ITT	101	96
COMPLETED	137	138
NOT COMPLETED	47	34
Subject withdrew consent	11	7
Lost to Follow-up	6	1
Death	12	10
Missing	18	16

[1]	"Started" indicates safety population.

Baseline Characteristics

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Reporting Groups

	Description
Cyclosporin A	The first administration of Cyclosporin A (CsA) was within the first 24 hours post-transplantation at an initial dose of 10-15mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally, via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the study, it was recommended that the dose of CsA was adjusted, as necessary, to achieve and maintain the C2 or C0 blood CsA concentration within the target ranges.
Tacrolimus	Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally or via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the course of the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain the C0 tacrolimus concentrations within target ranges.
Total	Total of all reporting groups

Baseline Measures

	Cyclosporin A	Tacrolimus	Total
Number of Participants [units: participants]	182	169	351
Age ^[1] [units: years] Mean ± Standard Deviation	54.4 ± 6.9	54.4 ± 7.1	54.4 ± 7.0
Age, Customized [units: Participants]
< 65 years	163	154	317
≥ 65 years	19	15	34
Gender [units: participants]
Female	57	48	105
Male	125	121	246

[1]	Baseline measurements were based on intent-to-treat population which included all patients as randomized that were transplanted, received at least one dose of study drug and had at least one post-baseline efficacy assessment.

Outcome Measures

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1. Primary:

Number of Participants With Fibrosis Score 2 or Above [Ishak-Knodell Fibrosis Score (FS) ≥ 2] Within 1 Year Post-transplant [ Time Frame: 1 year post-transplant ]

Show Outcome Measure 1

2. Secondary:

Number of Participants With Combined Endpoint of Death or Graft Loss or Fibrosis Score (FS) ≥ 2 [ Time Frame: 1 year post-transplant ]

Show Outcome Measure 2

3. Secondary:

Number of Participants With Fibrosing Cholestatic Hepatitis [ Time Frame: 1 year post-transplantation ]

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4. Secondary:

Number of Participants With Death, Graft Loss, Death or Graft Loss, Graft Loss With Re-transplantation [ Time Frame: 1 year post-transplant ]

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5. Secondary:

Number of Participants With Treated Acute Rejection, Biopsy Proven Acute Rejection (BPAR), and Sub-clinical Rejection [ Time Frame: 1 year post-transplant ]

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6. Secondary:

Number of Participants With Combined Endpoint of Death or Graft Loss or Biopsy Proven Acute Rejection (BPAR) [ Time Frame: 1 year post-transplant ]

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7. Secondary:

Number of Participants With Death or Re-transplantation Due to Recurrence of Hepatitis C Cirrhosis [ Time Frame: 1 year post-transplant ]

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8. Secondary:

Number of Participants With Fibrosis Score 2 or Above [Ishak-Knodell Fibrosis Score (FS) ≥ 2] Within 1 Year Post-transplant (Intent to Treat Population) [ Time Frame: 1 year post-transplant ]

Show Outcome Measure 8

9. Secondary:

Mean Value of Liver Function Tests at 1 Year Post-transplantation [ Time Frame: 1 year post-transplant ]

Show Outcome Measure 9

10. Secondary:

Log-transformed Hepatitis C Virus Ribonucleic Acid (HCV RNA) Values up to 1 Year Post Transplant [ Time Frame: Pre-transplant (Day 1), Day , Day 8, Day 29, Month 6 and 12 post- transplant ]

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11. Secondary:

Percentage of Participants With an Increase of at Least 1 Stage in Fibrosis [ Time Frame: Between 1 and 2 years ]

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12. Secondary:

Mean Fibrosis Score [ Time Frame: At 1and 2 years and its evolution over time ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
This study was prematurely discontinued due to poor recruitment. Since only a small patient group could be analyzed for primary outcome measure, robust conclusions on the effect of the two calcineurin inhibitors on the fibrosis score cannot be drawn.

Results Point of Contact:

Name/Title: Study coordinator
Organization: Novartis Pharmaceuticals
phone: 862-778-8300

No publications provided

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT00260208 History of Changes
Other Study ID Numbers:	COLO400A2426
Study First Received:	November 30, 2005
Results First Received:	September 14, 2011
Last Updated:	December 2, 2011
Health Authority:	United States: Institutional Review Board

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