Precision-Guided Tacrolimus Dosing for Heart Transplant Care

Not currently recruiting at 1 trial location

Overseen By Joseph E Rower, PhD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Utah

Must be taking: Immunosuppressants

Disqualifiers: Significant comorbidity, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve how doctors administer tacrolimus to children who have had a heart transplant. Tacrolimus (also known as FK506, Prograf, Advagraf, or Astagraf XL) helps prevent the body from rejecting the new heart, but determining the right dose can be challenging because it varies from person to person. The study uses a special software tool to help doctors decide the best dose for each patient, ensuring the drug works effectively without causing harm. Children over 6 months old and under 18, who have had a heart transplant due to certain heart problems, might be suitable for this trial. As an unphased trial, this study offers a unique opportunity to contribute to personalized medicine and improve dosing accuracy for future patients.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this precision medicine strategy for tacrolimus dosing is safe for pediatric heart transplant patients?

Research has shown that tacrolimus is generally well-tolerated by transplant patients. In studies involving children who received heart, liver, or kidney transplants, tacrolimus did not cause any unexpected side effects, which is reassuring.

The safety of tacrolimus has also been confirmed in adults. Specifically, studies on a similar version of tacrolimus, called Astagraf XL, in kidney transplant patients demonstrated good safety results over two years, with no new or unexpected problems. This suggests that tacrolimus is likely safe for heart transplant patients as well.

While all medications can have side effects, the evidence so far supports tacrolimus as a safe option for transplant care. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Precision-Guided Tacrolimus Dosing approach because it uses advanced decision support software to tailor medication doses more accurately for heart transplant patients. Unlike standard tacrolimus dosing methods that rely heavily on trial-and-error adjustments, this approach combines cutting-edge software recommendations with the physician's expertise to potentially enhance treatment precision. This could lead to more stable outcomes, reducing the risk of organ rejection and side effects, making it a promising development in post-transplant care.

What evidence suggests that this precision dosing strategy is effective for heart transplant care?

Research shows that tacrolimus helps prevent organ rejection in transplant patients. Studies have found that using an extended-release version, such as Astagraf XL, improves medication adherence because it requires only once-daily dosing. One study reported that after one year, 98.6% of patients remained alive, and 96.7% of transplanted organs functioned well. This suggests that tacrolimus, particularly in its extended-release form, is highly effective for transplant patients, including those with heart transplants. In this trial, participants in the Precision Tacrolimus arm will have their tacrolimus dose determined using a precision medicine decision support software tool. By adjusting the dose through personalized medicine, the researchers aim to enhance its effectiveness for each patient. ^{1 6 7 8 9}

Who Is on the Research Team?

Joseph E Rower, PhD

Principal Investigator

University of Utah

Are You a Good Fit for This Trial?

This trial is for children and teens between the ages of 6 months to less than 18 years who have had a heart transplant due to congenital heart malformation or cardiomyopathy. Participants must be willing and able to follow study procedures, without significant other health issues that would interfere with completing the study.

Inclusion Criteria

I have had a heart transplant due to a birth defect or heart muscle disease.

Exclusion Criteria

I am willing to follow all study procedures.

Significant comorbidity that would prevent study completion

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive precision-guided tacrolimus dosing to achieve target immunosuppression levels

6 weeks

Frequent visits for drug monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Tacrolimus
• Tacrolimus Dosing Support Tool

Trial Overview The trial is testing a new precision medicine strategy for dosing tacrolimus, an immunosuppressant drug used to prevent organ rejection in pediatric heart transplant patients. The aim is to tailor medication doses more accurately for each child's unique body characteristics.

How Is the Trial Designed?

Group I: Precision Tacrolimus Experimental Treatment 1 Intervention

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.

Tacrolimus is already approved in European Union, United States, Canada, Japan, Switzerland for the following indications:

Approved in European Union as Prograf for:

• Prevention of organ rejection in liver, kidney, and heart transplant patients

Approved in United States as Prograf for:

• Prevention of organ rejection in liver, kidney, and heart transplant patients

Approved in Canada as Advagraf for:

• Prevention of organ rejection in liver, kidney, and heart transplant patients

Approved in Japan as Prograf for:

• Prevention of organ rejection in liver, kidney, and heart transplant patients

Approved in Switzerland as Prograf for:

• Prevention of organ rejection in liver, kidney, and heart transplant patients

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4801790/

Overview of extended release tacrolimus in solid organ ... An extended release tacrolimus formulation known as Astagraf XL is now available which allows for once-daily dosing, with the potential to improve adherence.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6852421/

Efficacy and safety of prolonged‐release tacrolimus in ... This Phase 2 study assessed the efficacy and safety of PR‐T in stable pediatric kidney, liver, and heart transplant recipients (aged ≥5 to ≤16 years) over 1 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1600613522146149

One-Year Results with Extended-Release Tacrolimus/MMF ... One-year patient and graft survival were 98.6% and 96.7% in the XL/MMF group, 95.7% and 92.9% in TAC/MMF group and 97.6% and 95.7% in CsA/MMF group. The safety ...

4. reference.medscape.com reference.medscape.com/drug/prograf-astagraf-xl-tacrolimus-343207

Prograf, Astagraf XL (tacrolimus) dosing, indications, ... Prophylaxis of organ rejection in patients receiving allogeneic transplants; use with azathioprine or mycophenolate mofetil (MMF) recommended.

5. bpspubs.onlinelibrary.wiley.com bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.13952

Population pharmacokinetics of immediate‐ and prolonged ... The results support a 1 mg:1 mg conversion factor for switching patients from immediate-release tacrolimus (Prograf) to prolonged-release ...

6. fda.gov fda.gov/media/124118/download

NDA 204096/S-005 Astagraf XL Pediatric Studies The safety and efficacy of Astagraf XL have been established in adults, based on randomized, controlled clinical trials in de novo adult kidney ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1071916424007632

Utilization Of Extended Release Tacrolimus Formulations ... Of 25,019 who met study criteria only n=66 (0.26%) were treated with Tacrolimus ER, and n=141 (1.2%; cohort from 2018 onward) were treated with Tacrolimus LCP.

8. journals.lww.com journals.lww.com/transplantjournal/fulltext/2014/03270/long_term_follow_up_of_a_phase_iii_clinical_trial.7.aspx

Long-Term Follow-Up of a Phase III Clinical Trial ... Two-year data showed no unexpected safety or efficacy signals with Astagraf XL in renal transplant recipients (6). Since then, extended-release tacrolimus has ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3979830/

Long-Term Follow-Up of a Phase III Clinical Trial ... In the Astagraf XL, Prograf, and CsA groups, patient survival was 93.8% (95% CI: 90.5%, 97.2%), 93.2% (95% CI: 89.8%, 96.7%), and 92.5% (95% CI: 88.6%, 96.3%), ...