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A Randomized Multicenter Study Comparing a Tacrolimus-Based Protocol with and without Steroids in HCV-Positive Liver Allograft Recipients.

Neumann U, Samuel D, Trunečka P, Gugenheim J, Gerunda GE, Friman S - J Transplant (2012)

Bottom Line: Patient survival estimates were significantly lower with TAC/DAC than with TAC/STR (83.1 versus 95.5%; 95% CI, -0.227 to -0.019%), and graft survival was numerically lower (80.1 versus 91.1%, P = NS).Steroid-free immunosuppression had no real impact on HCV viral load.Results are inconclusive due to the unexpected lower completion rates in the TAC/DAC arm.

View Article: PubMed Central - PubMed

Affiliation: Department of General, Visceral and Transplantation Surgery, Charité, Campus Virchow Clinic, 13353 Berlin, Germany.

ABSTRACT
Allograft reinfection with hepatitis C virus (HCV) occurs universally in liver transplant recipients. Corticosteroids can contribute to HCV recurrence. This randomized study evaluated HCV recurrence in HCV-positive liver allograft recipients using steroid-free immunosuppression. All patients received tacrolimus (TAC) at an initial dose of 0.10-0.15 mg/kg. The steroid-free arm (TAC/daclizumab (TAC/DAC, n = 67)) received daclizumab induction, and the steroid arm (TAC/steroid (TAC/STR, n = 68)) received a steroid bolus (≤ 500mg) followed by 15-20 mg/day with discontinuation after month 3. Median HCV viral load at month 12, the primary endpoint, was similar at 5.46 (0.95-6.54) IU/mL with TAC/DAC and 5.91 (0.95-6.89) IU/mL with TAC/STR. Small numerical differences in the estimated rate of freedom from HCV recurrence (19.1 versus 13.8%) and freedom from biopsy proven rejection (78.4 versus 66.1%) were observed between TAC/DAC and TAC/STR. Patient survival estimates were significantly lower with TAC/DAC than with TAC/STR (83.1 versus 95.5%; 95% CI, -0.227 to -0.019%), and graft survival was numerically lower (80.1 versus 91.1%, P = NS). Completion rates (45 versus 82%) indicated poorer tolerability with TAC/DAC than with TAC/STR. Steroid-free immunosuppression had no real impact on HCV viral load. HCV recurrence was higher with TAC/STR. Results are inconclusive due to the unexpected lower completion rates in the TAC/DAC arm.

No MeSH data available.


Related in: MedlinePlus

Progress of liver transplant recipients through the phases of the randomized study comparing a tacrolimus-based protocol with and without steroids. The rate of study completion was lower with TAC/DAC than with TAC/STR. Most commonly, patients in the TAC/DAC arm prematurely discontinued the study due to an adverse event. TAC: tacrolimus; DAC: daclizumab; STR: steroids; FAS: full analysis set; PAS: primary analysis set.
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Related In: Results  -  Collection


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fig1: Progress of liver transplant recipients through the phases of the randomized study comparing a tacrolimus-based protocol with and without steroids. The rate of study completion was lower with TAC/DAC than with TAC/STR. Most commonly, patients in the TAC/DAC arm prematurely discontinued the study due to an adverse event. TAC: tacrolimus; DAC: daclizumab; STR: steroids; FAS: full analysis set; PAS: primary analysis set.

Mentions: The flow of patient progress through the study is outlined in Figure 1. Of 138 patients randomized to receive treatment, 135 were included in the FAS population. The rate of study completion was lower in the TAC/DAC arm at 45% (30 of 67 patients) than the rate of 82% (56 of 68 patients) in the TAC/STR arm. The main reason for premature withdrawal in both arms was an adverse event (Figure 1). Study discontinuation during week 1 was more common in the TAC/DAC arm (12 of 37 withdrawn patients) than in the TAC/STR arm (4 of 12 withdrawn patients). An erroneously administered steroid bolus at transplantation was the reason for 5 of the 6 protocol violations in the TAC/DAC group and a patient in the TAC/STR arm violated the protocol for receiving basiliximab. A baseline HCV viral load below the limit of quantification was documented in 17 patients in the TAC/DAC arm and in 16 patients in the TAC/STR arm and led to exclusion of these patients from the PAS. The PAS, therefore, comprised 50 patients in the TAC/DAC and 52 patients in the TAC/STR arm. Of these, 19 patients (38%) in the TAC/DAC arm and 35 patients (67%) in the TAC/STR arm completed the study and were used in the analysis of the primary endpoint.


A Randomized Multicenter Study Comparing a Tacrolimus-Based Protocol with and without Steroids in HCV-Positive Liver Allograft Recipients.

Neumann U, Samuel D, Trunečka P, Gugenheim J, Gerunda GE, Friman S - J Transplant (2012)

Progress of liver transplant recipients through the phases of the randomized study comparing a tacrolimus-based protocol with and without steroids. The rate of study completion was lower with TAC/DAC than with TAC/STR. Most commonly, patients in the TAC/DAC arm prematurely discontinued the study due to an adverse event. TAC: tacrolimus; DAC: daclizumab; STR: steroids; FAS: full analysis set; PAS: primary analysis set.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3368368&req=5

fig1: Progress of liver transplant recipients through the phases of the randomized study comparing a tacrolimus-based protocol with and without steroids. The rate of study completion was lower with TAC/DAC than with TAC/STR. Most commonly, patients in the TAC/DAC arm prematurely discontinued the study due to an adverse event. TAC: tacrolimus; DAC: daclizumab; STR: steroids; FAS: full analysis set; PAS: primary analysis set.
Mentions: The flow of patient progress through the study is outlined in Figure 1. Of 138 patients randomized to receive treatment, 135 were included in the FAS population. The rate of study completion was lower in the TAC/DAC arm at 45% (30 of 67 patients) than the rate of 82% (56 of 68 patients) in the TAC/STR arm. The main reason for premature withdrawal in both arms was an adverse event (Figure 1). Study discontinuation during week 1 was more common in the TAC/DAC arm (12 of 37 withdrawn patients) than in the TAC/STR arm (4 of 12 withdrawn patients). An erroneously administered steroid bolus at transplantation was the reason for 5 of the 6 protocol violations in the TAC/DAC group and a patient in the TAC/STR arm violated the protocol for receiving basiliximab. A baseline HCV viral load below the limit of quantification was documented in 17 patients in the TAC/DAC arm and in 16 patients in the TAC/STR arm and led to exclusion of these patients from the PAS. The PAS, therefore, comprised 50 patients in the TAC/DAC and 52 patients in the TAC/STR arm. Of these, 19 patients (38%) in the TAC/DAC arm and 35 patients (67%) in the TAC/STR arm completed the study and were used in the analysis of the primary endpoint.

Bottom Line: Patient survival estimates were significantly lower with TAC/DAC than with TAC/STR (83.1 versus 95.5%; 95% CI, -0.227 to -0.019%), and graft survival was numerically lower (80.1 versus 91.1%, P = NS).Steroid-free immunosuppression had no real impact on HCV viral load.Results are inconclusive due to the unexpected lower completion rates in the TAC/DAC arm.

View Article: PubMed Central - PubMed

Affiliation: Department of General, Visceral and Transplantation Surgery, Charité, Campus Virchow Clinic, 13353 Berlin, Germany.

ABSTRACT
Allograft reinfection with hepatitis C virus (HCV) occurs universally in liver transplant recipients. Corticosteroids can contribute to HCV recurrence. This randomized study evaluated HCV recurrence in HCV-positive liver allograft recipients using steroid-free immunosuppression. All patients received tacrolimus (TAC) at an initial dose of 0.10-0.15 mg/kg. The steroid-free arm (TAC/daclizumab (TAC/DAC, n = 67)) received daclizumab induction, and the steroid arm (TAC/steroid (TAC/STR, n = 68)) received a steroid bolus (≤ 500mg) followed by 15-20 mg/day with discontinuation after month 3. Median HCV viral load at month 12, the primary endpoint, was similar at 5.46 (0.95-6.54) IU/mL with TAC/DAC and 5.91 (0.95-6.89) IU/mL with TAC/STR. Small numerical differences in the estimated rate of freedom from HCV recurrence (19.1 versus 13.8%) and freedom from biopsy proven rejection (78.4 versus 66.1%) were observed between TAC/DAC and TAC/STR. Patient survival estimates were significantly lower with TAC/DAC than with TAC/STR (83.1 versus 95.5%; 95% CI, -0.227 to -0.019%), and graft survival was numerically lower (80.1 versus 91.1%, P = NS). Completion rates (45 versus 82%) indicated poorer tolerability with TAC/DAC than with TAC/STR. Steroid-free immunosuppression had no real impact on HCV viral load. HCV recurrence was higher with TAC/STR. Results are inconclusive due to the unexpected lower completion rates in the TAC/DAC arm.

No MeSH data available.


Related in: MedlinePlus