Evaluate the Clinical Benefits of EnvarsusXR in Post Liver Transplant

A Randomized Controlled Trial to Evaluate the Clinical Benefits of EnvarsusXR in Post Liver Transplant

This study will evaluate the medication adherence, clinical efficacy, and safety of EnvarsusXR in stable post liver transplant patient using a Phase III randomized controlled study. The primary outcome is change in medication adherence from baseline to the end of the study, assessed using a validated instrument (BAASIS- Basel Assessment of Adherence with Immunosuppressive medication Scales) and standard deviation of Tacrolimus levels.

Study Overview

• Status: Active, not recruiting
• Conditions: Post Liver Transplant
• Intervention / Treatment: Drug: EnvarsusXR; Drug: Tacrolimus

Detailed Description

The main aim of this study is to assess the immunosuppressant adherence, efficacy, and safety in post liver transplant patients converted from twice daily tacro to once daily EnvarsusXR. Tacrolimus trough level, clinical markers of liver disease, HbA1c , eGFR will be assessed at baseline, 1 week, 2 week, 4 week, 3 month and 6 months. Graft rejection will be assessed using routine standard guidelines to identify the cause. All patients post 1 year liver transplant, and within 5 years will be eligible to participate.

The primary hypothesis is that once daily dosing will improve medication adherence in patients randomized to the test arm as compared to the control arm, over a period of 9 months. The clinical efficacy will be assessed by no difference in standard deviation of tacrolimus in the two groups. The secondary hypothesis is that improved medication adherence will lead to improved patient reported quality of life (as assessed by PROMIS-29), and better health outcomes (as assessed by HbA1c, eGFR).

• Study Type: Interventional
• Enrollment (Anticipated): 35
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19141
      • Einstein Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who are 1 year post liver transplant, but within 5 years of transplant
• Serum Creatinine<= 2.5 mg/dl; AST,ALT, AP and GGT<=2 times ULN
• Patient must be on a stable tacrolimus dose, with tacrolimus trough levels between 5-12 ng/ml for 4 or more weeks before enrolment

Exclusion Criteria:

• Cognitive impairment which precludes participation
• Projected survival, in the opinion of the provider, of less than three months
• Any other solid organ transplant (kidney or pancreas)
• Use of any drug which is known to interfere with tacrolimus metabolism

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EnvarsusXR arm; Patients are converted to once daily EnvarsusXR (study drug). The patients continue taking this medication for 9 months of the study. Initial dosage will be 0.8 times the total daily dose of tacro bid, due to higher bioavailability. All subsequent dose adjustments will be based on maintenance of target tacro trough levels within range of 5-12 ng/ml.	Drug: EnvarsusXR; Patients randomized to study drug will be converted to EnvarsusXR once daily.; Other Names: Immunosuppression
Active Comparator: Standard of care arm; Post Liver Transplant patients take Tacrolimus twice daily as a part of standard of care. Those participating in the study will continue to take tacrolimus twice daily, as apart of their regular care. As a part of the study, they will complete the medication adherence and quality of life instruments.	Drug: Tacrolimus; Patients continue to take Tacrolimus BID, as a part of routine care.; Other Names: Standard of Care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Medication Adherence	Self reported using BAASIS instrument. BAASIS measures taking, skipping and dose reduction of drugs, with a recall period of 4 weeks. It consists of 4 questions with a 6 point response scale (ranging from never to every day). An additional overall adherence is ranked on a scale of 0 to 100 using a visual analog scale.	From baseline to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Quality of life	Self reported, using PROMIS-29. PROMIS is a result of the NIH support to develop a "psychometrically validated, dynamic system to measure QOL and patient reported outcomes in study participants. PROMIS-29 comprises a set of 29 questions evaluating seven QOL domains: Physical function, anxiety, depression, fatigue, sleep disturbance, social function and pain. The scores are reported as a T score (mean 50, SD=10) centered on the sample representative of 2000 US general census considering demographic variables.	From baseline to 6 months

Collaborators and Investigators

• Sponsor: Albert Einstein Healthcare Network
• Collaborators: Veloxis Pharmaceuticals
• Investigators: Study Director: Manisha Verma, MBBS, MPH, Einstein Healthcare Network

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2017
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: December 15, 2017
• First Submitted That Met QC Criteria: December 28, 2017
• First Posted (Actual): December 29, 2017

Study Record Updates

• Last Update Posted (Actual): January 8, 2021
• Last Update Submitted That Met QC Criteria: January 7, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: 5024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No