Precision Guided Tacrolimus Dosing in Pediatric Heart Transplant
July 8, 2026 updated by: Joseph Rower, University of Utah
Precision Pharmacokinetic-Guided Tacrolimus Dosing to Improve Pediatric Heart Transplant Outcomes
Immunosuppressive therapy is required to prevent organ rejection, however, dosing of immunosuppressive agents is complicated by patient-specific differences impacting the body's absorption and elimination of these agents.
The goal of this research proposal is to clinically validate an innovative precision medicine strategy for dosing the immunosuppressant tacrolimus in pediatric heart transplant, which will in turn lead to improvements in long-term transplant survival outcomes.
The strategy and techniques used in this project can be extended to improve drug therapy across multiple pediatric diseases requiring chronic therapy.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Of the more than 400 children annually receiving a heart transplant, the likelihood that the child dies within five years (25%) is equivalent to the potential that the child lives >20 years post-transplant.
The success of the transplant, and thus long-term survival of the child, is well known to correlate with achieving adequate immunosuppression to prevent rejection, especially in the period immediately following transplant.
Attaining adequate immunosuppression is complicated by several factors, many of which impact the pharmacokinetics (PK) of the immunosuppressive agent.
These factors include age of the patient, renal and hepatic function, concomitant medications, patient genetics, and the time post-transplant.
Frequent, invasive drug monitoring is used clinically to assess how these factors impact an individual child's PK, and in turn the dose required to achieve and maintain adequate immunosuppression.
However, this empirical "guess and check" approach often results in the child spending substantial time receiving immunosuppressive therapy that is either ineffective or unsafe, decreasing the longevity of the transplant organ and thus, long-term patient survival.
A more desirable approach would be to guide dosing using a precision medicine approach, wherein patient specific factors are used a priori to predict the dose most likely to achieve adequate immunosuppression.
Developing a precision medicine platform for immunosuppression following pediatric heart transplant has the potential to not only improve outcomes in heart transplant recipients, but across all transplant types.
This proposal aims to: 1) determine the impact of CYP3A5 genetic variation on tacrolimus concentrations in children, 2) prospectively validate the clinical utility of a PK-guided precision medicine platform in pediatric heart transplant patients receiving tacrolimus-based immunosuppression; and 3) identify and correlate biomarkers of transplant outcomes and tacrolimus safety/effect with the PK of tacrolimus, in order to establish the tacrolimus concentrations required for safe and effective immunosuppression in pediatric heart transplant recipients.
The overall objective of this study is to improve the long-term survival of children with heart transplant via optimization of the child's immunosuppressive therapy.
Importantly, the interdisciplinary nature of this mentored research proposal will facilitate my progress towards an independent career developing precision medicine tools to improve health outcomes in children.
Study Type
Interventional
Enrollment (Actual)
17
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Utah
-
Salt Lake City, Utah, United States, 84112
- University of Utah
-
Salt Lake City, Utah, United States, 84112
- Primary Children's Hospital
-
-
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
6 months to 18 years (Child, Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Age greater than 6 months and less than 18 years.
- Received heart transplant for congenital heart malformation or cardiomyopathy.
Exclusion Criteria:
- Unwillingness to complete study procedures.
- Significant comorbidity that would prevent study completion.
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: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Precision Tacrolimus
Participants in this arm of the study will have their tacrolimus dose determined using a precision medicine decision support software tool.
The participant's transplant physician will consider the recommended dose from the decision support tool in combination with the physician's expertise and experience to determine the proper tacrolimus dose for the participant.
|
The tacrolimus dosing support tool is based on a population pharmacokinetic model that incorporates patient specific factors including age, renal function, and concomitant medications.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Time to Target Concentration Attainment
Time Frame: Within 6 weeks following transplant
|
Target attainment will be defined concentrations within the target range (10-14 ug/L) and no dose modifications for 3 consecutive days.
Time to target concentration in the intervention arm will be compared to historical controls.
|
Within 6 weeks following transplant
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Joseph E Rower, PhD, University of Utah
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.
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)
May 1, 2020
Primary Completion (Actual)
April 30, 2025
Study Completion (Actual)
April 30, 2025
Study Registration Dates
First Submitted
May 5, 2020
First Submitted That Met QC Criteria
May 5, 2020
First Posted (Actual)
May 8, 2020
Study Record Updates
Last Update Posted (Actual)
August 3, 2026
Last Update Submitted That Met QC Criteria
July 8, 2026
Last Verified
July 1, 2026
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB_00124800
- K01HL148402 (U.S. NIH Grant/Contract)
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
No
Studies a U.S. FDA-regulated device product
Yes
product manufactured in and exported from the U.S.
No
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