Heart Transplant Failure and RejectionNCT04380311
Precision Guided Tacrolimus Dosing in Pediatric Heart Transplant
A study testing Tacrolimus Dosing Support Tool in people with Heart Transplant Failure and Rejection, run by University of Utah at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 6 months to 18 years
- Conditions the study is for
- Heart Transplant Failure and Rejection
- What is being tested?
- Tacrolimus Dosing Support Tool
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 May 2020to 30 Apr 2025
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age greater than 6 months and less than 18 years.
- Received heart transplant for congenital heart malformation or cardiomyopathy.
Who cannot join
- Unwillingness to complete study procedures.
- Significant comorbidity that would prevent study completion.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Primary Children's Hospital
Salt Lake City, Utah, 84112
University of Utah
Salt Lake City, Utah, 84112
About this study
Official title: 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.
Read the 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.
- Conditions
- Heart Transplant Failure and Rejection
- Being tested
- Tacrolimus Dosing Support Tool
- Keywords
- Tacrolimus, Pediatrics
- Medical subject headings
- Rejection, Psychology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tacrolimus Dosing Support ToolDevice
Also called Tacrolimus
The tacrolimus dosing support tool is based on a population pharmacokinetic model that incorporates patient specific factors including age, renal function, and concomitant medications.
| Study group | Role | What they receive |
|---|---|---|
| Precision Tacrolimus | Experimental | 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. Receives: Device: Tacrolimus Dosing Support Tool |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Target Concentration Attainment
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.
Measured: Within 6 weeks following transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2020
- Study start1 May 2020
- Primary completion30 Apr 2025
- Study completion30 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart Transplant Failure and RejectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Joseph Rower, University of Utah
- Investigators
- Joseph E Rower, PhD, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04380311
- Sponsor's protocol ID
- IRB_00124800
- Other IDs
- K01HL148402
- Status last verified
- Jul 2026
- First submitted
- 5 May 2020
- Last updated
- 3 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Rower JE, Stockmann C, Linakis MW, Kumar SS, Liu X, Korgenski EK, Sherwin CMT, Molina KM. Predicting tacrolimus concentrations in children receiving a heart transplant using a population pharmacokinetic model. BMJ Paediatr Open. 2017;1(1):e000147. doi: 10.1136/bmjpo-2017-000147. Epub 2017 Nov 22.
PubMed 29177199
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Precision Pharmacokinetic-Guided Tacrolimus Dosing to Improve Pediatric Heart Transplant Outcomes
- ClinicalTrials.gov ID
- NCT04380311
- Acronym / sponsor ID
- IRB_00124800
- Conditions
- Heart Transplant Failure and Rejection
- Keywords
- Tacrolimus, Pediatrics
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 1 May 2020 (actual)
- Primary completion
- 30 Apr 2025 (actual)
- Study completion
- 30 Apr 2025 (actual)
- First posted
- 8 May 2020 (actual)
- Results
- Posted 3 Aug 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Precision Tacrolimus | Experimental | Device: Tacrolimus Dosing Support ToolParticipants 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. |
Who may qualify
- Ages
- 6 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- Age greater than 6 months and less than 18 years.
- Received heart transplant for congenital heart malformation or cardiomyopathy.
Key exclusion criteria (2 listed)
- Unwillingness to complete study procedures.
- Significant comorbidity that would prevent study completion.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tacrolimus Dosing Support ToolAlso: TacrolimusThe tacrolimus dosing support tool is based on a population pharmacokinetic model that incorporates patient specific factors including age, renal function, and concomitant medications. | Device | Precision Tacrolimus |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 29177199Rower JE, Stockmann C, Linakis MW, Kumar SS, Liu X, Korgenski EK, Sherwin CMT, Molina KM. Predicting tacrolimus concentrations in children receiving a heart transplant using a population pharmacokinetic model. BMJ Paediatr Open. 2017;1(1):e000147. doi: 10.1136/bmjpo-2017-000147. Epub 2017 Nov 22.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph E Rower, PhD principal investigator
University of Utah
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Tacrolimus Dosing Support Tool in people with Heart Transplant Failure and Rejection, run by University of Utah at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Target Concentration Attainment (time frame: Within 6 weeks following transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04380311, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2026.