End Stage Liver Disease, Hepatitis C
Conditions
Keywords
Hepatitis C Virus, Immunosuppressive Agents
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.
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 If patients respond to treatment, the virus is no longer active.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.
Interventions
DRUGDaclizumub
anti-rejection drug
DRUGTacrolimus
anti rejection drug
DRUGCyclosporine
anti rejection drug
DRUGMMF
anti rejection drug
Sponsors
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
Baylor Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Countries
United States
Participant flow
Recruitment details
Recruitment period August 15, 2002-March 29, 2004 Recruitment of liver transplant receipeints from centers transplant program
Pre-assignment details
Subjects must be receiving a liver transplant for end stage chronic HCV
Participants by arm
| Arm | Count |
|---|---|
| Treatment Arm 1 Immunosuppression TAC (tacrolimus) and CS (cyclosporine) | 80 |
| Treatment Arm 2 Immunosuppression MMF(mofetil mycophenolate), TAC (tacrolimus) and CS (cyclosporine) | 79 |
| Treatment Arm 3 Immunosuppression DAC (daclizumub), MMF (mofetil mycophenolate)and TAC (tacrolimus) | 153 |
| Total | 312 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 12 | 14 | 19 |
| Overall Study | graft loss | 4 | 1 | 2 |
| Overall Study | Lost to Follow-up | 1 | 3 | 10 |
| Overall Study | Non Compliance | 1 | 0 | 0 |
| Overall Study | Other reason | 0 | 1 | 3 |
| Overall Study | Physician Decision | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 3 | 2 |
Baseline characteristics
| Characteristic | Treatment Arm 2 | Treatment Arm 3 | Treatment Arm 1 | Total |
|---|---|---|---|---|
| Age, Customized Years | 51.4 years STANDARD_DEVIATION 7.8 | 51.5 years STANDARD_DEVIATION 7.4 | 51.7 years STANDARD_DEVIATION 7.2 | 51.6 years STANDARD_DEVIATION 7.4 |
| Gender Female | 19 Participants | 44 Participants | 24 Participants | 87 Participants |
| Gender Male | 60 Participants | 109 Participants | 56 Participants | 225 Participants |
| Reduce HCV recurrent post liver transplant | 79 participants | 153 participants | 80 participants | 312 participants |
| Region of Enrollment United States | 79 Participants | 153 Participants | 80 Participants | 312 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 80 | 79 / 79 | 153 / 153 |
| serious Total, serious adverse events | 12 / 80 | 14 / 79 | 14 / 153 |
Outcome results
Primary
Freedom From Acute Rejection or HCV Recurrence or Treatment Failure
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Arm 1 | Freedom From Acute Rejection or HCV Recurrence or Treatment Failure | 69 participants |
| Treatment Arm 2 | Freedom From Acute Rejection or HCV Recurrence or Treatment Failure | 70 participants |
| Treatment Arm 3 | Freedom From Acute Rejection or HCV Recurrence or Treatment Failure | 133 participants |
Primary
Freedom From HCV Recurrence Within First Year That Requires HCV Antiviral Therapy and Freedom From Treatment Failure
Participants would have their blood drawn and tested for the HCV virus to determine if they had recurrence
Time frame: 12 month post transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Arm 1 | Freedom From HCV Recurrence Within First Year That Requires HCV Antiviral Therapy and Freedom From Treatment Failure | 39 participants |
| Treatment Arm 2 | Freedom From HCV Recurrence Within First Year That Requires HCV Antiviral Therapy and Freedom From Treatment Failure | 39 participants |
| Treatment Arm 3 | Freedom From HCV Recurrence Within First Year That Requires HCV Antiviral Therapy and Freedom From Treatment Failure | 72 participants |