Everolimus bAsed caLcineurin inhibiTor frEe immunosuppRession oNe year AfTer lIver transplantatiON (ALTERNATION) – a randomized, prospective, multicenter, open-label, controlled trial.

• Applicant: Privatdozent Dr. Richard Taubert
• Subject Area: Gastroenterology ; General and Visceral Surgery
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 512689161

Although immunosuppression after liver transplantation prevents rejection of the transplant, it can also irreversibly damage kidney function and promote infections and cancer. Aftercare with reduced immunosuppression or with immunosuppressants with less kidney damage, such as the so-called mTOR inhibitors, protects the kidney function, but is associated with an increased rejection rate. A strict preselection of liver transplanted patients with a low risk of rejection, based on a liver biopsy, among other clinical parameters, was able to show in uncontrolled studies that kidney function was spared without an increased risk of rejection in the context of such reduced immunosuppression. The current study is intended to test the hypothesis, that preselecting patients with a low risk of rejection by means of a liver biopsy, enables a significant reduction in immunosuppression with preservation of kidney function without an increased risk of rejection in a national, multi-center, prospective, randomized and controlled study. After signs of rejection had been ruled out in a surveillance biopsy of the liver transplant, a total of 150 patients will be randomly assigned to two study arms. A comparison arm, which corresponds to standard immunosuppression with a so-called calcineurin inhibitor, and a study arm, which corresponds to reduced immunosuppression with an mTOR inhibitor. After one year, the effect of the two treatment arms on renal function and the prevention of rejection of the liver transplant will be compared. If the patient does not show an increased risk of rejection after one year, the treatment arms should be continued for a further two years after a second immunosuppression minimization step in order to also examine the medium-term effects on kidney function and the prevention of rejection. In addition, the occurrence of infections and cancer as well as the quality of life in the two study arms are to be recorded and compared in order to further assess typical side effects of immunosuppression after liver transplantation.

• DFG Programme: Clinical Trials
• Co-Investigator: Dr. Sophia Heinrich