Renal Tubular Injury and Transplant Outcomes in Cardiac Recipients Converting From IR Tacrolimus to XR Tacrolimus

NCT ID: NCT04917718

Last Updated: 2022-04-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-16
• Study Completion Date: 2024-12-31

Brief Summary

Immediate release (IR) tacrolimus peaks in the first two hours after administration. These peak levels are influenced by CYP3A5 expression with expressors requiring higher total daily doses with higher peak levels compared to non-expressors. Tacrolimus XR (Envarsus) is a once daily formulation with delayed absorption and lower peak levels while maintaining similar trough levels as seen with IR tacrolimus. A randomized trial of conversion from IR tacrolimus to tacrolimus XR in kidney transplant recipients have shown similar efficacy and adverse events between the two groups but no improvement in estimated GFR. However, urinary biomarkers of acute kidney injury associated with changes in tacrolimus dosing may be more sensitive then serum creatinine. The objective of this study is to assess renal tubular injury in heart transplant recipients who are converted from immediate release to tacrolimus XR. The hypothesis is that the delayed absorption and lower peak levels of tacrolimus XR will lead to less tubular injury and improved renal function without increased risk to the heart allograft.

Detailed Description

The primary outcome is change in urinary NGAL expression with conversion from IR tacrolimus to tacrolimus XR. In aim 1, changes in urinary biomarkers of tubular injury at 4 weeks after conversion to tacrolimus XR with stable trough levels will be assessed. These changes will be assessed by CYP3A5 expressor category that will be determined by genotyping of a single gene for variants. The changes in GFR using the creatinine-cystatin C CKD-EPI equation will be assessed. In aim 2, the rate of rejection as defined as treated rejection within the last 30 days for any grade > 1R or AMR or acute graft dysfunction (LV ejection fraction drop > 10%) will be looked. The cardiac allograft vasculopathy based on coronary angiography +/- IVUS and right heart catheterization hemodynamics at baseline and 1 year post conversion will also be evaluated. In addition to changes in cardiac function, the changes in blood pressure, serum glucose, and cholesterol in the first year after conversion will be assessed.

Conditions

Chronic Kidney Diseases; Heart Transplant

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Extended Release Tacrolimus

All participants who consent to the study will be in this group.

Group Type: EXPERIMENTAL

Conversion from IR Tacrolimus to XR Tacrolimus

Intervention Type: DRUG

All participants will be consented to the study on IR Tacrolimus. After their baseline visit, they will be converted to XR Tacrolimus

Interventions

Conversion from IR Tacrolimus to XR Tacrolimus

All participants will be consented to the study on IR Tacrolimus. After their baseline visit, they will be converted to XR Tacrolimus

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Stable, heart-only transplant recipient within 10 years of transplantation
• 18 -80 years old
• Currently taking IR Tacrolimus
• Baseline eGFR> 30mL/min/1.73m2

Exclusion Criteria

• Multiple organ transplant recipients
• Less than 18 years old
• Greater than 80 years old
• Heart-only transplants recipients with active malignancy, rejection, or greater than 10 years from transplantation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Veloxis Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Loyola University

OTHER

Sponsor Role: lead

Responsible Party

Sanjeev Akkina

MD, Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sanjeev Akkina, MD

Role: PRINCIPAL_INVESTIGATOR

Loyola University

Locations

Loyola University Medical Center

Maywood, Illinois, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Sanjeev Akkina, MD

Role: CONTACT

sanjeev.akkina@lumc.edu

708-327-4897

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Other Identifiers

212781

Identifier Type: -

Identifier Source: org_study_id