NCT06280950

Expanding Liver Transplant Immunosuppression Minimization Via Everolimus

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 340 (estimated)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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. 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.

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.

Conditions

• Liver Transplant

Interventions

Type	Name	Description
DRUG	Everolimus	* 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.
DRUG	Tacrolimus (continued reduction)	* 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
DRUG	Tacrolimus (maintain 50% reduction)	\- Participants randomized in this cohort maintain initial reduced dose of Tacrolimus and everolimus for study duration.
DRUG	Everolimus	* 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.

Timeline

• Start date: 2024-09-12
• Primary completion: 2027-06-01
• Completion: 2029-06-01
• First posted: 2024-02-28
• Last updated: 2025-05-31

Locations

8 sites across 1 country: United States

Regulatory

• FDA-regulated drug study