Study of Liver Transplant For End-Stage Liver Disease Caused By Chronic Hepatitis C Infection

• Sponsor: Baylor Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00163657
• Collaborator: Baylor Health Care System (Other), Emory University (Other), University of Southern California (Other), Mayo Clinic - Scottsdale/Phoenix, Arizona (Other), New York Presbyterian Hospital (Other), Oregon Health and Science University (Other), New York University (Other), University of Cincinnati (Other), University of Alabama at Birmingham (Other), The University of Texas Health Science Center at San Antonio (Other), University of Chicago (Other), University of California, San Francisco (Other), Mayo Clinic - Rochester, Minnesota (Other), Medical University of South Carolina (Other), University of Virginia (Other), Lahey Clinic (Other), University of Medicine and Dentistry of New Jersey (Other), Northwestern Memorial Hospital (Other)
• Enrollment: 312
• Location: 1
• Arms: 3
• Duration (Months): 54
• Patients Per Site Per Month: 5.8

Study Details

Study Description

Brief Summary

The purpose of this study is to compare three treatment regimens in patients who have received a liver transplant for end-stage liver disease caused by Chronic Hepatitis C infection.

Condition or Disease	Intervention/Treatment	Phase
End Stage Liver Disease; Hepatitis C	Drug: Daclizumub; Drug: Tacrolimus; Drug: Cyclosporine; Drug: MMF	Phase 4

Detailed Description

End-stage liver disease due to Hepatitis C virus (HCV) infection is the most common reason for liver transplantation in the United States. Patients who have HCV will always carry the virus in their body. If patients respond to treatment, the virus is no longer active. This means that although the virus is still present, it is not currently causing damage to their liver.

Because recurrence of HCV is virtually universal in HCV positive transplant recipients and is associated with long term, possibly lethal complications, the search for the most appropriate therapies must also include methods to prevent or minimize recurrence or disease progression, if the goal of improving long term outcomes for these patients is to be achieved.

Corticosteroids and high doses of immunosuppressive agents have been associated with increased rates of HCV recurrence. Finding a regimen that provides adequate immunosuppression to prevent early and late rejection episodes, and minimizes steroid usage as well as high doses of other immunosuppressive agents is highly desirable.

This study is being conducted to determine the most effective immunosuppressive regimen that will prevent allograft rejection, minimize adverse events and at the same time, prevent or reduce the incidence of HCV recurrence following liver transplant.

Study Design

• Study Type: Interventional
• Actual Enrollment: 312 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Randomized, Prospective Multicenter Study To Compare The Efficacy And Safety Among 3 Immunosuppressant Treatment Regimens In Patients Receiving A Liver Transplant For ESLD Caused By Chronic Hepatitis C
• Study Start Date: Jul 1, 2002
• Actual Primary Completion Date: Apr 1, 2006
• Actual Study Completion Date: Jan 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: tacrolimus and cyclosporine immunosuppressant treatment regimens the intervention is antirejection treatment with the above labeled drugs tacrolimus and cyclosporine	Drug: Daclizumub; anti-rejection drug; Other Names: Zenapax ; Drug: Tacrolimus; anti rejection drug; Other Names: Prograf
Active Comparator: MMF, tacrolimus and cyclosporine immunosuppressant treatment regimensthe intervention is antirejection treatment with the above labeled drugs MMF tacrolimus and cyclosporine	Drug: Tacrolimus; anti rejection drug; Other Names: Prograf ; Drug: Cyclosporine; anti rejection drug; Other Names: Neoral ; Drug: MMF; anti rejection drug; Other Names: mycophenolate mofetil
Active Comparator: daclizumub, MMFand tacrolimus immunosuppressant treatment regimens	Drug: Daclizumub; anti-rejection drug; Other Names: Zenapax ; Drug: Tacrolimus; anti rejection drug; Other Names: Prograf ; Drug: MMF; anti rejection drug; Other Names: mycophenolate mofetil

Outcome Measures

Primary Outcome Measures

1. Freedom From Acute Rejection or HCV Recurrence or Treatment Failure [12 months]

   Freedom from acute rejection (Banff>grade 2 with RAI score>4) or freedom from HCV recurrence (Batts/Ludwig>Stage 2, or >Grade 3) that requires HCV antiviral therapy or treatment failure (patient death, graft loss, premature withdrawal from study regimen or treatment with more than 1 dose of corticosteroids for presumptive rejection without a biopsy to confirm the rejection; reported values represent the "Number of participants with Freedom From Acute Rejection or HCV Recurrence or Treatment Failure"

2. Freedom From HCV Recurrence Within First Year That Requires HCV Antiviral Therapy and Freedom From Treatment Failure [12 month post transplant]

   Participants would have their blood drawn and tested for the HCV virus to determine if they had recurrence

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patient has been fully informed and has signed an IRB approved informed consent form and is willing and able to follow study procedures for the full 2 years.

2. Patient is a recipient of a primary whole/split, cadaveric/living donor liver transplant for end stage chronic Hepatitis C.

3. Patient is > age 18.

4. Female patients of child bearing potential must have a negative urine or serum pregnancy test upon hospitalization or within 7 days prior to enrollment and have agreed to utilize effective birth control throughout the study as well as for 6 weeks following study completion.

Exclusion Criteria:

1. Patient has previously received or is receiving an organ transplant other than a liver.

2. Patient has received a liver transplant from a Hepatitis B core antibody or a Hepatitis C antibody positive donor.

3. Patient has received an ABO (blood group anti A, anti B antibodies) incompatible donor liver.

4. Patient has fulminant liver failure with a life expectancy without a liver transplant of less than 7 days as defined by UNOS (Adult Patient Status 1, UNOS Policy 3.6.4.1: See Appendix C).

5. Patient has renal dysfunction pre-transplant that, in the opinion of the investigator, will prohibit the use of calcineurin inhibitors within 72 hours post transplant.

6. Patient is intubated, on vasopressors, is ICU bound, or has experienced a significant blood loss (greater than 5 units) 72 hours prior to transplant procedure.

7. Recipient or donor is seropositive for human immunodeficiency virus (HIV) or HbsAg positive serology.

8. Patient is to receive antilymphocyte antibody induction therapy, such as ATGAM (lymphocyte immune globulin), OKT3 (muromonab-CD3), Simulect (basiliximab), or Thymoglobulin.

9. Patient has a known hypersensitivity to Prograf (TAC), HCO-60, CellCept (MMF), Zenapax or corticosteroids.

10. Patient is pregnant or lactating.

11. Patient has participated in a blinded trial or participated in a trial involving a non-marketed (investigational) drug within 3 months of enrollment.

12. Patient has participated in a trial involving a market drug within 30 days. However, patients who participated in any interferon or ribavirin trials are permitted.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Baylor Regional Transplant Institute - Baylor University Medical Center	Dallas	Texas	United States	75246

Sponsors and Collaborators

• Baylor Research Institute
• Baylor Health Care System
• Emory University
• University of Southern California
• Mayo Clinic - Scottsdale/Phoenix, Arizona
• New York Presbyterian Hospital
• Oregon Health and Science University
• New York University
• University of Cincinnati
• University of Alabama at Birmingham
• The University of Texas Health Science Center at San Antonio
• University of Chicago
• University of California, San Francisco
• Mayo Clinic - Rochester, Minnesota
• Medical University of South Carolina
• University of Virginia
• Lahey Clinic
• University of Medicine and Dentistry of New Jersey
• Northwestern Memorial Hospital

Investigators

• Principal Investigator: Goran Klintmalm, MD, Baylor Univeristy Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Baylor Research Institute
• ClinicalTrials.gov Identifier: NCT00163657
• Other Study ID Numbers: 02-01-L; ZEN159
• First Posted: Sep 14, 2005
• Last Update Posted: Jan 12, 2017
• Last Verified: Nov 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Baylor Research Institute: Hepatitis C Virus; Immunosuppressive Agents
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Liver Diseases; End Stage Liver Disease; Cyclosporine; Mycophenolic Acid; Tacrolimus; Cyclosporins

Study Results

Participant Flow

Recruitment Details	Recruitment period August 15, 2002-March 29, 2004 Recruitment of liver transplant receipeints from centers transplant program
Pre-assignment Detail	Subjects must be receiving a liver transplant for end stage chronic HCV

Arm/Group Title	Treatment Arm 1	Treatment Arm 2	Treatment Arm 3
Arm/Group Description	Immunosuppression TAC (tacrolimus) and CS (cyclosporine)	Immunosuppression MMF(mofetil mycophenolate), TAC (tacrolimus) and CS (cyclosporine)	Immunosuppression DAC (daclizumub), MMF (mofetil mycophenolate)and TAC (tacrolimus)
Period Title: Overall Study
STARTED	80	79	153
COMPLETED	60	56	116
NOT COMPLETED	20	23	37

Baseline Characteristics

Arm/Group Title	Treatment Arm 1	Treatment Arm 2	Treatment Arm 3	Total
Arm/Group Description	Immunosuppression TAC (tacrolimus) and CS (cyclosporine)	Immunosuppression MMF(mofetil mycophenolate), TAC (tacrolimus) and CS (cyclosporine)	Immunosuppression DAC (daclizumub), MMF (mofetil mycophenolate)and TAC (tacrolimus)	Total of all reporting groups
Overall Participants	80	79	153	312
Age, Customized (years) [Mean (Standard Deviation) ]
Years	51.7 (7.2)	51.4 (7.8)	51.5 (7.4)	51.6 (7.4)
Gender (Count of Participants)
Female	24 30%	19 24.1%	44 28.8%	87 27.9%
Male	56 70%	60 75.9%	109 71.2%	225 72.1%
Region of Enrollment (Count of Participants)
United States	80 100%	79 100%	153 100%	312 100%
Reduce HCV recurrent post liver transplant (participants) [Number]
Number [participants]	80 100%	79 100%	153 100%	312 100%

Outcome Measures

1. Primary Outcome

Title	Freedom From Acute Rejection or HCV Recurrence or Treatment Failure
Description	Freedom from acute rejection (Banff>grade 2 with RAI score>4) or freedom from HCV recurrence (Batts/Ludwig>Stage 2, or >Grade 3) that requires HCV antiviral therapy or treatment failure (patient death, graft loss, premature withdrawal from study regimen or treatment with more than 1 dose of corticosteroids for presumptive rejection without a biopsy to confirm the rejection; reported values represent the "Number of participants with Freedom From Acute Rejection or HCV Recurrence or Treatment Failure"
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Arm 1	Treatment Arm 2	Treatment Arm 3
Arm/Group Description	Immunosuppression TAC (tacrolimus) and CS (cyclosporine)	Immunosuppression MMF(mofetil mycophenolate), TAC (tacrolimus) and CS (cyclosporine)	Immunosuppression DAC (daclizumub), MMF (mofetil mycophenolate)and TAC (tacrolimus)
Measure Participants	80	79	153
Number [participants]	69 86.3%	70 88.6%	133 86.9%

2. Primary Outcome

Title	Freedom From HCV Recurrence Within First Year That Requires HCV Antiviral Therapy and Freedom From Treatment Failure
Description	Participants would have their blood drawn and tested for the HCV virus to determine if they had recurrence
Time Frame	12 month post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Arm 1	Treatment Arm 2	Treatment Arm 3
Arm/Group Description	Immunosuppression TAC (tacrolimus) and CS (cyclosporine)	Immunosuppression MMF(mofetil mycophenolate), TAC (tacrolimus) and CS (cyclosporine)	Immunosuppression DAC (daclizumub), MMF (mofetil mycophenolate)and TAC (tacrolimus)
Measure Participants	80	79	153
Number [participants]	39 48.8%	39 49.4%	72 47.1%

Adverse Events

Time Frame	24 months
Adverse Event Reporting Description	biopsy, labs
Arm/Group Title	Treatment Arm 1		Treatment Arm 2		Treatment Arm 3
Arm/Group Description	Immunosuppression TAC (tacrolimus) and CS (cyclosporine)		Immunosuppression MMF(mofetil mycophenolate), TAC (tacrolimus) and CS (cyclosporine)		Immunosuppression DAC (daclizumub), MMF (mofetil mycophenolate)and TAC (tacrolimus)
All Cause Mortality
	Treatment Arm 1		Treatment Arm 2		Treatment Arm 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Treatment Arm 1		Treatment Arm 2		Treatment Arm 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/80 (15%)		14/79 (17.7%)		14/153 (9.2%)
General disorders
Death	12/80 (15%)	12	14/79 (17.7%)	14	14/153 (9.2%)	19
Graft loss	4/80 (5%)	4	1/79 (1.3%)	1	2/153 (1.3%)	2
Other (Not Including Serious) Adverse Events
	Treatment Arm 1		Treatment Arm 2		Treatment Arm 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/80 (15%)		79/79 (100%)		153/153 (100%)
General disorders
thrombocytopenia	5/80 (6.3%)	6	40/79 (50.6%)	45	80/153 (52.3%)	85
neutropenia	3/80 (3.8%)	4	40/79 (50.6%)	45	70/153 (45.8%)	75
anemia	4/80 (5%)	5	40/79 (50.6%)	45	10/153 (6.5%)	13

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.