for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
completion around
Principal Investigator
by Sandy Feng, MD
Headshot of Sandy Feng
Sandy Feng



This is a study to determine the safety, efficacy, and tolerability of taking away the anti-rejection medicine, tacrolimus, in liver transplant recipients in conjunction with everolimus monotherapy to preserve renal function. Two hundred - seventy (270) subjects will be randomized 2:1 into one of two groups between 2-3 months post-transplant. Seventy participants will be placed into an observational group and will remain on their current post-transplant medications. The duration of the study from time of enrollment is 18-20 months.

Official Title

Expanding Liver Transplant Immunosuppression Minimization Via Everolimus (CTOT-43)


This study is a multicenter 2:1 randomized nonblinded phase II interventional clinical trial in liver transplant recipients. The primary objective is to determine the safety, efficacy, and tolerability of tacrolimus minimization and eventual withdrawal in conjunction with everolimus monotherapy to preserve renal function. Study subjects will undergo first reduction of tacrolimus with the addition of everolimus. If everolimus is tolerated, subjects will be randomized 2:1 into one of two interventional arms. The first interventional arm will under a stepwise reduction of tacrolimus and be on everolimus monotherapy for the remainder of the study. The second interventional arm will remain on the initial reduced tacrolimus dose and everolimus. If subjects prior to randomization are unable to tolerate everolimus, these subjects will be placed in the observational group. These subjects will stop taking everolimus and resume their immunosuppression therapy prior to study enrollment.


Liver Transplant, Liver, Transplant, Everolimus, Tacrolimus, Tacrolimus (continued reduction), Tacrolimus (maintain 50% reduction)


You can join if…

Open to people ages 18 years and up

  1. Subject and/or legal guardian must be able to understand and provide informed consent
  2. Adult recipient of first liver transplant alone (de novo)
  3. Estimated glomerular filtration rate >=30 ml/min/1.73m2 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

You CAN'T join if...

  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 of Hepatic Artery Thrombosis or Portal Vein Thrombosis.
  6. Chronic use of systemic glucocorticoids, biological immunomodulatory therapy, or other immunosuppressive agents other than per study protocol
  7. History of hepatitis B or C virus infection with detectable viral PCR at enrollment
  8. History of prior organ transplantation (liver or other type)
  9. 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
  10. Active treatment with any mTOR-inhibitor agent (everolimus, sirolimus)
  11. 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/microL or actively being treated with GCSF; Hb <8.0; platelet count <50K); serum triglycerides > 1000 mg/dL; other per PI)
  12. 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
  13. Pregnant on enrollment or plan to become pregnant during the study period
  14. 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
  15. Received live attenuated vaccine(s) within 2 months of enrollment
  16. 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
  17. 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.


  • UCSF (Site #: 71108)
    San Francisco California 94143 United States
  • Mayo Clinic Hospital Arizona (Site #: 71144)
    Phoenix Arizona 85054 United States

Lead Scientist at UCSF

  • Sandy Feng, MD
    Dr. Sandy Feng is a transplant surgeon who performs liver, kidney and pancreas transplants. In her research, Feng studies transplantation tolerance, a transplant recipient's ability to maintain normal organ function with minimal or no use of immunosuppressive drugs.


not yet accepting patients
Start Date
Completion Date
National Institute of Allergy and Infectious Diseases (NIAID)
Phase 2 Liver Transplant Research Study
Study Type
Expecting 340 study participants
Last Updated