Expanding Liver Transplant Immunosuppression Minimization Via Everolimus

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Feb 20, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new approach to managing medications for people who have received a liver transplant. The goal is to see if it's safe and effective to stop using a common anti-rejection medication called tacrolimus and instead use a different medication, everolimus, to help protect kidney function. The trial will involve 270 participants who will be divided into two groups: one group will switch to everolimus, while the other group will continue their current medications. The study will last for about 18 to 20 months.

To participate, individuals need to be adults who are receiving their first liver transplant and must meet certain health criteria, such as having a specific level of kidney function. Participants will need to provide informed consent and agree to follow the study guidelines, which may include using contraception if they are of childbearing age. Throughout the study, participants will be closely monitored to ensure their safety and to gather important information about how well the new treatment works. This trial is currently recruiting participants, so those interested should discuss it with their healthcare provider.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Subject and/or legal guardian must be able to understand and provide informed consent
• • 2. Adult (age greater than or equal to 18 years of age at time of informed consent) recipient of first liver transplant alone (de novo)
• • 3. Estimated glomerular filtration rate \>=30 ml/min/1.73m\^2 at enrollment using the CKD-EPI 2021 equation
• • 4. Treatment with tacrolimus therapy, with or without mycophenolic acid derivatives and/or corticosteroids
• • 5. Female subjects of childbearing potential with negative pregnancy test upon study entry
• • 6. All subjects of reproductive potential agreeing to use contraception for the duration of the study
• • 7. Previous vaccination or documented immunity to varicella, measles, hepatitis B, pneumococcus, influenza, zoster (if \>=19 years old), and 2019-nCoV (COVID-19) as outlined in the DAIT Vaccination Guideline
• Exclusion Criteria:
• • 1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol
• • 2. Active unresolved systemic viral, bacterial, fungal, or parasitic infection requiring oral or intravenous anti-infective therapy
• • 3. History of autoimmune liver disease including autoimmune hepatitis, primary sclerosing cholangitis, and/or primary biliary cirrhosis, or other contraindications to drug withdrawal
• • 4. History of non-hepatic autoimmune disease requiring current or future systemic immunosuppressive therapy other than per study protocol
• • 5. History post-transplant of Hepatic Artery Thrombosis or Portal Vein Thrombosis.
• • 6. History of recurrent cirrhosis after liver transplantation.
• • 7. Chronic use of systemic glucocorticoids, biological immunomodulatory therapy, or other immunosuppressive agents other than per study protocol
• • 8. History of hepatitis B or C virus infection with detectable viral PCR at enrollment
• • 9. History of prior organ transplantation (liver or other type)
• • 10. History of \>= 2 biopsy-proven acute cellular rejection episodes of any severity, \>=1 moderate to severe rejection episode (histologically defined or requiring lymphodepletion therapy), or \>= 1 antibody- mediated rejection episode
• • 11. Active treatment with any mTOR-inhibitor agent (everolimus, sirolimus)
• • 12. Contraindication to treatment with everolimus (open wound or wound infection; urine protein: creatinine ratio \> 0.5; significant pancytopenia (any of the following: WBC \<1.5 K/uL or ANC \<1000 cells/uL or actively being treated with GCSF; Hb \<8.0; platelet count \<50K); serum triglycerides \> 1000 mg/dL; other per PI)
• • 13. Abnormal liver function tests on study entry: Total Bilirubin (TB)\>1.5 mg/dL and Direct Bilirubin (DB) \>1.0 mg/dL, Alkaline Phosphatase (AP) \>200 U/L, and Alanine Aminotransaminase (ALT)\>60 U/L
• • 14. Pregnant on enrollment or plan to become pregnant during the study period
• 15. Participation in another clinical trial that would interfere with this study's procedures and intervention:
• • 1. Use of investigational biologic or drug (within 8 weeks of study enrollment)
• • 2. Additional blood collection that would exceed research blood draw limits
• • 3. Any other procedure or intervention, in the investigator's opinion would interfere with this study
• • 16. Received live attenuated vaccine(s) within 2 months of enrollment
• • 17. Current, diagnosed, mental illness or current, diagnosed, or self-reported drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study
• • 18. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.