Conversion of Maintenance Prograf to Envarsus in Liver Transplant Recipients

NCT05655273 | Enrolling By Invitation Phase 4

• 1 other identifier: 22-5210
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Prograf and Envarsus are two different formulations of Tacrolimus which is used as an immunosuppressant in liver transplant (LT) patients. Prograf is currently used as part of the standard immunosuppression regimen for LT recipients at UHN. This study will compare the use of Prograf and Envarsus and their effects on liver and renal function, trough tacrolimus levels, drug-related adverse effects, and patient adherence. Trial design is a pilot randomized trial. The study aims to recruit 40 patients from UHN's LT program and they will be randomized 1:1 to either stay on their current dose of Prograf or be converted to a once-daily equivalent dose of Envarsus. Both groups of patients will be followed for 48 weeks. This study will compare the change from baseline to week 48 in liver and renal function, tacrolimus-related side effects and patient reported outcomes between the two study groups.

Conditions

Liver Transplant Rejection; Immune System Suppression

Keywords

liver transplant; tacrolimus toxicity; drug conversion; tacrolimus; prograf; envarsus

Outcome Measures

Primary Outcomes (6)

• Change in AST levels

  Baseline to week 12

• Change in ALT levels

  Baseline to week 12

• Change in ALP levels

  Baseline to week 12

• Change in Bilirubin blood levels

  Baseline to week 12

• Change in tacrolimus trough levels

  Baseline to week 12

• Change in overall daily dose of tacrolimus

  Baseline to week 12

Secondary Outcomes (13)

• Change in Systolic Blood Pressure

  Baseline to week 24 and week 48

• Change in Diastolic Blood Pressure

  Baseline to week 24 and week 48

• Change in Renal function (eGFR)

  Baseline to week 24 and week 48

• Change in tremor severity (for subset of patients who report significant tremor at baseline)

  Baseline to week 24 and week 48

• Change in glycemic control (HbA1c)

  Baseline to week 24 and week 48

Study Arms (2)

Post-liver transplant patients receiving Prograf

ACTIVE COMPARATOR

Drug: Prograf

Post-liver transplant patients receiving Envarsus

ACTIVE COMPARATOR

Drug: Envarsus

Interventions

Prograf DRUG

Participants randomized to the Prograf (control) arm will continue with their current twice daily dosing of Prograf.

Post-liver transplant patients receiving Prograf

Envarsus DRUG

Participants randomized to Envarsus arm will have their current daily dose of Prograf converted to once-daily Envarsus dose according to the following ratio: 0.7 x the current daily Prograf dose. Envarsus is available in 3 dose strengths- 0.75mg, 1.0mg, and 4.0mg. The actual dose of Envarsus will be rounded to an amount that can be administered using the above tablet strengths.

Post-liver transplant patients receiving Envarsus

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult (\>18 years) prevalent liver transplant recipient
• \>12 months after liver transplant
• Prograf-based maintenance immunosuppression with targeted tacrolimus trough level of 5-10 ug/L
• Stable liver allograft function (defined as ASL \& ALT \<30, Bilirubin \<20 \& ALP\<150 at baseline visit or within 4 weeks of baseline visit)
• Stable renal function (creatinine \< 180 µmol/l and eGFR \> 40 ml/min) at baseline visit (or within 4 weeks of baseline visit)
• No episode of acute rejection within 6 months of baseline visit
• Elevated creatinine (defined as \>ULN) OR Significant symptoms (by patient self-report) potentially associated with tacrolimus (eg. tremor, difficulty to concentrate, insomnia) OR difficulty to adhere to a twice daily regimen

You may not qualify if:

• Multiorgan transplant;
• severe intercurrent illness;
• severe cognitive impairment (all as determined by clinical team);
• unwilling to consent.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Paladin Labs Inc.: collaborator

Study Sites (1)

Toronto General Hospital

Toronto, Ontario, M5G2N2, Canada

Location

MeSH Terms

Interventions

Tacrolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Nazia Selzner, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: conversion v. control

Study Record Dates

• First Submitted: November 22, 2022
• First Posted: December 19, 2022
• Study Start: January 1, 2024
• Primary Completion: April 30, 2025
• Study Completion: February 28, 2026
• Last Updated: December 11, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)