MedTrace Logo

SRL (Sirolimus) Withdrawal

NCT02062944 · Status: COMPLETED · Phase: NA · Type: INTERVENTIONAL · Enrollment: 21

Last updated 2022-07-14

Study results available
· View outcomes & findings →

Summary

The significance of this clinical trial lies in its potential to increase the success of immunosuppression (IS) therapy withdrawal in liver transplant (LT) recipients, thus decreasing the negative impact of IS on their long-term outcomes. Lifetime immunosuppression (IS) with standard agents, the calcineurin inhibitors (CNI) cyclosporine and tacrolimus (TAC), is currently required at clinically recommended doses and trough levels to prevent allograft rejection. However, this occurs at the significant expense of long-term CNI toxicity, i.e. chronic kidney disease (CKD), hypertension, hyperlipidemia, diabetes, infections and malignancy. With improvements in early graft and patient survival, long term adverse IS effects have become increasingly important in this rapidly expanding patient population. The strategies to reduce long term CNI toxicity include dose minimization that still leaves patients on CNI therapy, conversion to non-CNI therapy, or even complete IS withdrawal. The second approach, conversion to non-CNI IS therapy, is attractive in the potential to stabilize or improve renal function and other CNI toxicities. One such non-nephrotoxic IS agent, the mammalian target of rapamycin inhibitor (mTOR-I) SRL, has a different mechanism of IS action and studies have shown that CNI to SRL conversion can stabilize renal dysfunction with a low risk of rejection. Yet even with these possible benefits, patients on SRL are still subject to lifetime IS therapy with side effects and costs, highlighting the need to investigate the strategies that promote full IS withdrawal without rejection (3rd approach), also known as 'operational tolerance'.

Conditions

  • Acute Rejection of Liver Transplant
  • Effects of Immunosuppressant Therapy

Interventions

DRUG

Sirolimus

SRL minimization will be performed if clinically, biochemically and histologically stable. Patients entering the minimization phases will be reduced every month by 50% of total dose of Sirolimus until they reach .5mg daily for one month. Then .5 mg every other day, then twice weekly, the once weekly dosing. This should take approximately 6 month to complete minimization. Liver function tests will be monitored every 2 weeks. For any patient developing liver dysfunction, liver biopsy will be performed. Patients will then be completely withdrawn and followed post-withdrawal for 12 months.

Sponsors & Collaborators

Principal Investigators

  • Josh Levitsky, MD · Northwestern University

Study Design

Allocation
NA
Purpose
DIAGNOSTIC
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Max Age
75 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2013-03-31
Primary Completion
2020-07-31
Completion
2020-07-31

Countries

  • United States

Study Locations

More Related Trials

Entities

Companies

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02062944 on ClinicalTrials.gov