Conversion of Maintenance Prograf to Envarsus in Liver Transplant Recipients

NCT ID: NCT05655273

Last Updated: 2024-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ENROLLING_BY_INVITATION

Clinical Phase

PHASE4

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-01-01

Study Completion Date

2026-02-28

Brief Summary

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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.

Detailed Description

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Tacrolimus (Prograf ©) has become part of the standard of care for patients receiving solid organ transplants and is part of the immunosuppressive protocol (along with prednisone and mycophenolate mofetil \[CellCept ©\]) used by liver transplant recipients at University Health Network (UHN). Tacrolimus is associated with several toxicities including renal injury, tremor, pancreatic islet β-cell injury (leading to diabetes) and hyperlipidemia. As a result of these potential toxicities, careful therapeutic drug monitoring of tacrolimus is a key component of post-transplant management. Tacrolimus trough levels are known to correlate with total tacrolimus exposure, as shown from formal pharmacokinetic assessments. Accordingly, trough serum concentrations of tacrolimus are measured routinely in all recipients and are used to guide dosing. The Prograf formulation of tacrolimus has a short serum half-life and must be dosed twice daily to maintain therapeutic serum concentrations. Further, Prograf administration results in a high peak tacrolimus level. Peak tacrolimus levels have been shown to correlate with toxicity; thus, avoidance of high peaks may be desirable to minimize tacrolimus toxicity.

Envarsus is an extended-release formulation of tacrolimus that provides similar drug exposure to tacrolimus at a 30% lower dose but with a once daily dosing regimen. Envarsus dosing also results in a lower peak tacrolimus level compared to Prograf. In this way, it is hoped that Envarsus may provide similar therapeutic efficacy as Prograf but with fewer adverse effects. In addition, the simpler dosing regimen is expected to enhance patient adherence and quality of life.

The present study is aimed at evaluating the impact of a switch from Prograf to Envarsus on liver and renal function, trough tacrolimus levels, drug-related adverse effects and adherence. It hypothesizes that once daily Envarsus can be substituted at reduced daily dose for twice daily Prograf in stable liver transplant recipients without clinically meaningful changes in liver allograft function while reducing tacrolimus side effects, reducing cumulative daily dose of the drug and increasing adherence to treatment and quality of life.The results of this study have the potential to change current practice. 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

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Liver Transplant Rejection Immune System Suppression

Keywords

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liver transplant tacrolimus toxicity drug conversion tacrolimus prograf envarsus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

conversion v. control
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Post-liver transplant patients receiving Prograf

Group Type ACTIVE_COMPARATOR

Prograf

Intervention Type DRUG

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

Post-liver transplant patients receiving Envarsus

Group Type ACTIVE_COMPARATOR

Envarsus

Intervention Type 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.

Interventions

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Prograf

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

Intervention Type DRUG

Envarsus

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

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

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Paladin Labs Inc.

OTHER

Sponsor Role collaborator

University Health Network, Toronto

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nazia Selzner, MD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Locations

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Toronto General Hospital

Toronto, Ontario, Canada

Site Status

Countries

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Canada

Other Identifiers

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22-5210

Identifier Type: -

Identifier Source: org_study_id