XR Tacrolimus for Heart Transplant Recipients

Overseen By Sanjeev Akkina, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Loyola University

Must be taking: IR Tacrolimus

Disqualifiers: Multiple organ transplants, Malignancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new formulation of tacrolimus, a medication that prevents organ rejection in heart transplant patients. The study aims to determine if the extended-release version of tacrolimus, taken once daily, causes less kidney damage than the regular version. It seeks heart transplant recipients who have been stable for up to 10 years and are currently taking the immediate-release form of tacrolimus. Participants will switch to the extended-release version to assess its potential to better protect kidneys without affecting their heart transplant. As a Phase 4 trial, this research involves an FDA-approved treatment and seeks to understand its benefits for more patients, offering a chance to contribute to valuable insights.

Will I have to stop taking my current medications?

The trial requires participants to switch from their current immediate release (IR) tacrolimus to the extended release (XR) version. It doesn't specify about other medications, so you may not need to stop them.

What is the safety track record for Tacrolimus XR?

In a previous study, researchers found that patients who switched from immediate release (IR) tacrolimus to extended release (XR) tacrolimus, such as Envarsus, experienced similar safety outcomes. The study showed no significant difference in side effects between the two groups, indicating that XR tacrolimus is generally well-tolerated.

Another study reported that although serious side effects occurred, the rates were similar across different forms, including extended release. This suggests that the risks are not higher with XR tacrolimus compared to other forms. XR tacrolimus is designed to have lower peak levels in the bloodstream, potentially reducing side effects related to high doses.

In summary, studies have shown that XR tacrolimus is safe, with no increased risks compared to the standard IR version. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

XR Tacrolimus is unique because it offers an extended-release formulation, which means it can be taken less frequently than traditional tacrolimus. This could lead to better medication adherence and more stable drug levels in the bloodstream, reducing the risk of rejection for heart transplant patients. Researchers are excited about this treatment as it could potentially improve patient convenience and outcomes by maintaining consistent immunosuppression with fewer daily doses.

What evidence suggests that tacrolimus XR is effective for heart transplant recipients?

Research has shown that the extended-release form of tacrolimus, Envarsus XR, works well for transplant recipients, including those with heart transplants. In this trial, all participants will receive the extended-release tacrolimus. Studies have found that taking this medication once daily is as effective as the more frequent version for protecting the transplanted organ. It maintains steady levels in the body, which may help prevent kidney damage. Specifically, one study found that patients using extended-release tacrolimus had similar survival rates, indicating it helps keep the transplanted organ healthy. Additionally, most people tolerate it well, usually without serious side effects. ^{1 6 7 8 9}

Who Is on the Research Team?

Sanjeev Akkina, MD

Principal Investigator

Loyola University

Are You a Good Fit for This Trial?

This trial is for heart transplant recipients aged 18-80, within 10 years post-transplant, currently on IR Tacrolimus with stable function and a baseline kidney filtration rate (eGFR) over 30. It excludes those under 18 or over 80, with active cancer, recent rejection episodes, multiple organ transplants or more than a decade since their heart transplant.

Inclusion Criteria

I am currently on IR Tacrolimus medication.

Your kidney function, measured as eGFR, is higher than 30 mL/min/1.73m2.

I received a heart transplant within the last 10 years and my condition is stable.

Exclusion Criteria

I am under 18 years old.

I had a heart transplant over 10 years ago, or I have cancer or rejection issues post-transplant.

I have received transplants for more than one organ.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are converted from immediate release tacrolimus to extended release tacrolimus and monitored for changes in urinary biomarkers of tubular injury

4 weeks

1 visit (in-person) for conversion and monitoring

Follow-up

Participants are monitored for changes in cardiac function, blood pressure, serum glucose, and cholesterol levels

1 year

Regular visits (in-person) for monitoring

What Are the Treatments Tested in This Trial?

Interventions

• Tacrolimus

Trial Overview The study tests the effects of switching from Immediate Release (IR) Tacrolimus to Extended Release (XR) Tacrolimus in heart transplant patients. The goal is to see if XR Tacrolimus causes less kidney tubular injury due to its lower peak levels but similar overall exposure as IR.

How Is the Trial Designed?

Group I: Extended Release Tacrolimus Experimental Treatment 1 Intervention

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

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?

Loyola University

Lead Sponsor

Trials

161

Recruited

31,400+

Veloxis Pharmaceuticals

Industry Sponsor

Trials

43

Recruited

3,200+

Citations

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

Overview of extended release tacrolimus in solid organ ... The published data supporting the use of extended release tacrolimus in heart transplant recipients is limited, yet current evidence does not signal that the ...

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

Efficacy and safety of prolonged‐release tacrolimus in ... Evidence from clinical studies suggests that prolonged‐release tacrolimus is effective and well tolerated in adult transplant recipients converted from the ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0272638615013451

Novel Once-Daily Extended-Release Tacrolimus Versus ... 1-year data from this trial showed the noninferiority of a novel once-daily extended-release tacrolimus (LCPT; Envarsus XR) to immediate-release tacrolimus (IR- ...

4. 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 ...

5. jmcp.org jmcp.org/doi/10.18553/jmcp.2021.27.7.948

Cost-effectiveness of once-daily vs twice-daily tacrolimus ... Overall results for both groups show that LCPT is incrementally more costly and more effective compared with IR-Tac, indicating a trade-off scenario.

6. 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.

7. 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 ... At least one serious adverse event was reported in the majority of patients in each group during the study (65.9% Astagraf XL, 69.8% Prograf, and 65.6% CsA).

8. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/21/NCT03194321/ICF_001.pdf

A Prospective, Pilot Trial to Evaluate Safety and Tolerability ... We are doing this study to determine the safety and tolerability of tacrolimus extended-release. (Astagraf XL) in the highly sensitized patient population as ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/204096s009lbl.pdf

ASTAGRAF XL (tacrolimus) Label - accessdata.fda.gov Safety data from the TPRI and postmarketing surveillance suggest infants exposed to tacrolimus in utero have an increased risk for miscarriage, pre-term ...