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

April 12, 2022 updated by: Sanjeev Akkina, Loyola University

Assessment of Renal Tubular Injury and Transplant Outcomes in Cardiac Recipients Converting From Immediate Release Tacrolimus to Extended Release Tacrolimus.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

42

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Illinois
      • Maywood, Illinois, United States, 60153
        • Recruiting
        • Loyola University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Extended Release Tacrolimus
All participants who consent to the study will be in this group.
Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Urinary neutrophil gelatinase-associated lipocalin (NGAL)
Time Frame: 4 weeks
Change in Urinary NGAL level (ng/mL)
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Estimated Glomerular Filtration Rate (eGFR)
Time Frame: 4 weeks
Change in eGRF level by the Creatinine-Cystatin C CKD-EPI equation (mL/min/1.73m2)
4 weeks
Microalbuminuria
Time Frame: 4 weeks
Change in Urine albumin-creatinine ratio
4 weeks
CYP3A5 expressor category
Time Frame: Baseline
CYP3A5 genotyping to determine expressor category
Baseline
Heart transplant rejection
Time Frame: 1 year
The rate of rejection as defined as treated rejection within the last 30 days for any grade>1R, AMR, or acute graft dysfunction (LVEF drop greater than 10%)
1 year
Cardiac allograft vasculopathy
Time Frame: 1 year
The rate of cardiac allograft vasculopathy based on coronary angiography with or without IVUS and right heart catheterization hemodynamics
1 year
Blood pressure
Time Frame: 1 year
Change in blood pressure (mmHg)
1 year
Serum glucose
Time Frame: 1 year
Change in serum glucose levels (mg/dL)
1 year
LDL Cholesterol
Time Frame: 1 year
Change in LDL cholesterol level (mg/dL)
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Loyola University

Collaborators

Veloxis Pharmaceuticals

Investigators

  • Principal Investigator: Sanjeev Akkina, MD, Loyola University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 16, 2021

Primary Completion (Anticipated)

December 31, 2024

Study Completion (Anticipated)

December 31, 2024

Study Registration Dates

First Submitted

June 2, 2021

First Submitted That Met QC Criteria

June 2, 2021

First Posted (Actual)

June 8, 2021

Study Record Updates

Last Update Posted (Actual)

April 13, 2022

Last Update Submitted That Met QC Criteria

April 12, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 212781

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.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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