December 12, 2011
The liver transplantation (ITN030ST Shaked) trial recently completed enrollment with a total of 275 participants. This particular trial is a phase II trial to Assess the Safety of Immunosuppression Withdrawal in Liver Transplant Recipients, and is the largest liver transplant trial undertaken by the ITN. It is also one of the largest non-pharmaceutical trials in liver transplantation ever achieved.
This trial investigates the relationship between clinical outcomes and immune responses in liver transplant recipients with hepatitis C infection or nonimmune nonviral causes of liver failure who have been maintained on, or withdrawn from, immunosuppression. The trial also examines the clinical and mechanistic outcomes of attempting to withdraw immunosuppression in a broad group of transplant recipients and relate those to a conventionally treated group in whom immunosuppression is maintained. As part of the trial, participants undergo liver transplantation and receive immunosuppression with a calcineurin inhibitor and corticosteroids. Corticosteroids are tapped in the three months after transplantation and the calcineurin inhibitor is continued; meanwhile recipients are regularly assessed for evidence of allograft rejection. One year after transplantation, participants eligible for withdrawal are randomly assigned in a 4 to 1 ratio to immunosuppression withdrawal or to maintenance. Participants assigned to withdrawal undergo a scheduled taper over approximately one year.
To date, three participants have remained off immunosuppression drugs for between 22 and 137 weeks. Specifically, two HCV participants (individuals with previous liver failure due to the hepatitis C infection) have been on no immunosuppression for over 2 years—121 and 137 weeks, respectively. Additionally, six HCV participants are actively withdrawing from immunosuppressant medication. Furthermore, one NINV (individuals with pervious liver failure due to nonimmune nonviral causes) have been without immunosuppressant medication for over 22 weeks, while an additional 15 NINV participants are actively withdrawing.
These ongoing results are important because one of the biggest causes of liver transplantation failure is due to hepatitis C infection which naturally weakens the body’s defense. To be able to show tolerance among this high risk patient population is landmark. Among the many other insights gained from this trial was that by studying immune-tolerance response in liver transplant recipients, the researchers incidentally also learned about immunosuppression minimization through safety parameters of monotherapy and that once a day dosing has shown to be efficacious.
Additional noteworthy accomplishments from this trial include two abstracts presented at the International Liver Transplantation Society (ILTS) Meeting in June 2011 in Valencia, Spain. Dr. Avi Shaked presented Lessons Learned from the ITN030ST Immunosuppression Withdrawal Trial in Liver Transplant Recipients; and Dr. Sandy Feng presented Evolution of Donor Specific Alloantibodies (DSA) with Immunosuppression Withdrawal among Adult Liver Transplant Recipients in ITN030.
Congratulations on these impressive milestones in immunosuppression withdrawal in liver transplant recipients, and wish the team continued success as participants continue through the follow-up phase of the trial.
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