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Liver TransplantPhase 2ELIMINATENCT06280950

Expanding Liver Transplant Immunosuppression Minimization Via Everolimus

A Phase 2 study testing Everolimus, Tacrolimus (continued reduction) and Tacrolimus (maintain 50% reduction) in people with Liver Transplant, run by National Institute of Allergy and Infectious Diseases (NIAID) at 12 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Liver Transplant
What is being tested?
Everolimus, Tacrolimus (continued reduction) and Tacrolimus (maintain 50% reduction)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
340 participants
Where
12 sitesUnited States
Study dates
12 Sep 2024to 30 Jun 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subject and/or legal guardian must be able to understand and provide informed consent
  • Adult (age greater than or equal to 18 years of age at time of informed consent) recipient of first liver transplant alone (de novo)
  • Estimated glomerular filtration rate >=30 ml/min/1.73m^2 at enrollment using the CKD-EPI 2021 equation
  • Treatment with tacrolimus therapy, with or without mycophenolic acid derivatives and/or corticosteroids
  • Female subjects of childbearing potential with negative pregnancy test upon study entry
  • All subjects of reproductive potential agreeing to use contraception for the duration of the study
  • 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

Who cannot join

  • Inability or unwillingness of a participant to give written informed consent or comply with study protocol
  • Active unresolved systemic viral, bacterial, fungal, or parasitic infection requiring oral or intravenous anti-infective therapy
  • History of autoimmune liver disease including autoimmune hepatitis, primary sclerosing cholangitis, and/or primary biliary cirrhosis, or other contraindications to drug withdrawal
  • History of non-hepatic autoimmune disease requiring current or future systemic immunosuppressive therapy other than per study protocol
  • History post-transplant of Hepatic Artery Thrombosis or Portal Vein Thrombosis.
  • History of recurrent cirrhosis after liver transplantation.
Show all 21Show fewer
  • Chronic use of systemic glucocorticoids, biological immunomodulatory therapy, or other immunosuppressive agents other than per study protocol
  • History of hepatitis B or C virus infection with detectable viral PCR at enrollment
  • History of prior organ transplantation (liver or other type)
  • 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
  • Active treatment with any mTOR-inhibitor agent (everolimus, sirolimus)
  • Contraindication to treatment with everolimus (open wound or wound infection; urine protein: creatinine ratio > 0.5 mg/mg; 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)
  • 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
  • Pregnant on enrollment or plan to become pregnant during the study period
  • Participation in another clinical trial that would interfere with this study's procedures and intervention:
  • Use of investigational biologic or drug (within 8 weeks of study enrollment)
  • Additional blood collection that would exceed research blood draw limits
  • Any other procedure or intervention, in the investigator's opinion would interfere with this study
  • Received live attenuated vaccine(s) within 2 months of enrollment
  • 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
  • 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.

Trial locations and contacts

12 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Tracia Debnam, MS contact

301-761-7414

Tracia.debnam@nih.gov

12 sites in 1 country

United States12 sites, 12 recruiting

  • University of Michigan (Site #: 71154)

    Ann Arbor, Michigan, 48109

    Sasha Shingina, MD

    Recruiting

  • Northwestern University (Site #: 71110)

    Chicago, Illinois, 60611

    Justin Boike, MD

    Recruiting

  • Baylor Medical Center (Site #: 71153)

    Dallas, Texas, 75246

    Robert Rahimi, MD

    Recruiting

  • Duke University Medical Center (Site #: 71139)

    Durham, North Carolina, 27710

    Matthew Kappus, MD

    Recruiting

  • Houston Methodist (Site #: 71120)

    Houston, Texas, 77030

    Mark Ghobrial, MD

    Not yet recruiting

  • Ronald Regan at UCLA Medical Center (Site #: 71123)

    Los Angeles, California, 90095

    Sammy Saab, MD

    Not yet recruiting

  • Icahn School of Medicine at Mount Sinai (Site #: 71115)

    New York, New York, 10029

    Thomas Schiano, MD

    Recruiting

  • University of Pennsylvania (Site #: 71111)

    Philadelphia, Pennsylvania, 19104

    Abraham Shaked, MD

    Recruiting

  • Mayo Clinic Hospital Arizona (Site #: 71144)

    Phoenix, Arizona, 85054

    Hugo Vargas, MD

    Recruiting

  • University of Pittsburgh Medical Center (Site #: 71170)

    Pittsburgh, Pennsylvania, 15260

    Scott Biggins, MD

    Recruiting

  • University of California, San Diego (Site #: 71179)

    San Diego, California, 92121

    Pranab Barman, MD

    Recruiting

  • University of California, San Francisco (Site #: 71108)

    San Francisco, California, 94143

    Sandy Feng, MD

    Recruiting

Other trials in United States

About this study

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

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.

Read the detailed description

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 undergo 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.

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

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EverolimusDrug

    Also called Zortress

    • The first step is the addition of everolimus to participants in this group pre-randomization.
    • Participants on a mycophenolate compound will stop taking it within 7 days of initiating everolimus, either by immediate discontinuation or a 7-day taper.
    • Participants taking prednisone will taper off prednisone by 6 months post-transplant.
    • The second step is tacrolimus minimization and withdrawal to everolimus monotherapy in this group after randomization.

  • Tacrolimus (continued reduction)Drug

    Also called FK-506, FR-900506, Prograf, Prograft

    • Participants randomized in this cohort will have their tacrolimus dose reduced by 50% following randomization.
    • They will maintain this daily dose for 4 weeks/1 month (28-30 days). Tacrolimus withdrawal will occur in intervals of 30 days or 4 weeks.
    • Each subsequent reduction will be based on LFT stability over the prior time interval before the next reduction

  • Tacrolimus (maintain 50% reduction)Drug

    Also called FK-506, FR-900506, Prograf, Prograft

    • Participants randomized in this cohort maintain initial reduced dose of Tacrolimus and everolimus for study duration.

  • EverolimusDrug

    Also called Zortress

    • The first step is the addition of everolimus to participants in the interventional group pre-randomization.
    • Participants on a mycophenolate compound will stop taking it within 7 days of initiating everolimus, either by immediate discontinuation or a 7-day taper.
    • Participants taking prednisone will taper off prednisone by 6 months post-transplant.
    • The second step is to continue on the reduced tacrolimus and everolimus regimen.
Study groups in NCT06280950
Study groupRoleWhat they receive
Interventional Group 1ExperimentalParticipants in this group will slowly reduce their dose of tacrolimus and continue everolimus as their only immunosuppression medication.
Receives: Drug: Everolimus; Drug: Tacrolimus (continued reduction)
Interventional Group 2ExperimentalParticipants in this group will continue to take reduced Tacrolimus and Everolimus IS regimen.
Receives: Drug: Tacrolimus (maintain 50% reduction); Drug: Everolimus
Observational GroupNo interventionParticipants in this group could not tolerate the addition of everolimus. These participants will not be randomized. * Participants in this group will stop taking everolimus. * Participants in this group will resume taking their tacrolimus +/- mycophenolate compound and prednisone immunosuppression regimen.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percent change in estimated glomerular filtration rate (eGFR) by CKD-EPI 2021 equation. Between Cohorts INT-1 and INT-2

    Measured: From Visit 2 to Visit 9 (12 months post-liver transplant)

  2. Proportion of subjects with treated Biopsy Proven Acute Rejection (tBPAR) per local pathology. Between cohorts INT-1 and INT-2

    Measured: From Visit 2 to Visit 9 (12 months post-liver transplant)

Secondary outcomes (22)

  1. Percent change in estimated Glomerular Filtration Rate (eGFR)

    Measured: From Visit 1 to Visit 11 (20 months post-liver transplant)

  2. Percentage of subjects with treated Biopsy Proven Acute Rejection (tBPAR)

    Measured: From Visit 1 to Visit 11 (20 months post-liver transplant)

  3. Changes in liver graft function: Total bilirubin

    Measured: From Visit 1 to Visit 11 (20 months post-liver transplant)

  4. Changes in liver graft function: Direct bilirubin

    Measured: From Visit 1 to Visit 11 (20 months post-liver transplant)

  5. Changes in liver graft function: Alanine Aminotransaminase (ALT)

    Measured: From Visit 1 to Visit 11 (20 months post-liver transplant)

  6. Changes in liver graft function: Aspartate Aminotransferase (AST)

    Measured: From Visit 1 to Visit 11 (20 months post-liver transplant)

  7. Changes in liver graft function: Alkaline Phosphatase

    Measured: From Visit 1 to Visit 11 (20 months post-liver transplant)

  8. Time to graft failure in liver function defined as relisting for transplantation, re-transplantation itself or death with failed graft

    Measured: From Visit 1 to Visit 11 (20 months post-liver transplant)

  9. Time to all-cause mortality

    Measured: From Visit 1 to Visit 11 (20 months post-liver transplant)

  10. Proportion of subjects experiencing a Major Adverse Cardiac Event (MACE)

    Measured: From Visit 1 to Visit 11 (20 months post-liver transplant)

  11. Proportion of subjects experiencing infection requiring hospitalization

    Measured: From Visit 1 to Visit 11 (20 months post-liver transplant)

  12. Proportion of subjects experiencing any malignancy

    Measured: From Visit 1 to Visit 11 (20 months post-liver transplant)

  13. Proportion of subjects developing severe Estimated Glomerular Filtration Rate (eGFR) deterioration >40 percent from baseline using the CKD-EPI 2021 equation

    Measured: From Visit 1 to Visit 11 (20 months post-liver transplant)

  14. Proportion of subjects developing any major immunosuppressive therapy complications

    Measured: From Visit 1 to Visit 11 (20 months post-liver transplant)

  15. Proportion of subjects developing new onset peripheral edema

    Measured: From Visit 1 to Visit 11 (20 months post-liver transplant)

  16. Proportion of subjects developing new onset cytopenia deemed WBC <3.0x10^9 /L, Hb <8.0 g/dL, or platelets <50 x 10^9/L.

    Measured: From Visit 1 to Visit 11 (20 months post-liver transplant)

  17. Proportion of subjects developing new onset oral/gastrointestinal ulcerations

    Measured: From Visit 1 to Visit 11 (20 months post-liver transplant)

  18. Proportion of subjects developing new onset gastrointestinal symptoms (nausea, vomiting, abdominal pain, or diarrhea) related to everolimus therapy.

    Measured: From Visit 1 to Visit 11 (20 months post-liver transplant)

  19. Proportion of subjects developing new onset pneumonitis

    Measured: From Visit 1 to Visit 11 (20 months post-liver transplant)

  20. Proportion of subjects developing new onset hepatic artery thrombosis

    Measured: From Visit 1 to Visit 11 (20 months post-liver transplant)

  21. Proportion of subjects developing other adverse events deemed

    Measured: From Visit 1 to Visit 11 (20 months post-liver transplant)

  22. Proportion of subjects developing any adverse events related to everolimus therapy

    Measured: From Visit 1 to Visit 11 (20 months post-liver transplant)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Feb 2024
  2. Study start12 Sep 2024
  3. Primary completion30 Jun 2028 (estimated)
  4. Study completion30 Jun 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
340 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06280950
Sponsor's protocol ID
DAIT CTOT-43
Acronym
ELIMINATE
Status last verified
Nov 2026
First submitted
20 Feb 2024
Last updated
5 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Everolimus, Tacrolimus (continued reduction) and Tacrolimus (maintain 50% reduction) in people with Liver Transplant, run by National Institute of Allergy and Infectious Diseases (NIAID) at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Tracia Debnam, MS (301-761-7414, Tracia.debnam@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent change in estimated glomerular filtration rate (eGFR) by CKD-EPI 2021 equation. Between Cohorts INT-1 and INT-2 (time frame: From Visit 2 to Visit 9 (12 months post-liver transplant)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06280950.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.

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