Extended-Release Tacrolimus for Kidney Transplant Recipients

(Neuro-KTR Trial)

Overseen By Sul A Lee, MD, MS

Age: 65+

Sex: Any

Trial Phase: Phase 4

Sponsor: Massachusetts General Hospital

Must be taking: Tacrolimus

Disqualifiers: Dementia, Parkinson's, Cancer, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new version of the medication tacrolimus, used by kidney transplant patients to prevent organ rejection. The study aims to determine if the extended-release version of tacrolimus, taken less frequently, affects thinking and memory differently than the regular version. Participants will either continue with their current tacrolimus or switch to the extended-release version. This trial suits kidney transplant recipients who have been stable on their medication for at least a year and regularly visit the Massachusetts General Hospital transplant center. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, helping to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires participants to be on immediate-release tacrolimus as part of their treatment.

What is the safety track record for extended-release tacrolimus?

Research has shown that extended-release tacrolimus (Envarsus XR) is generally well-tolerated by kidney transplant patients. Studies have found that diarrhea, low red blood cell count (anemia), and urinary tract infections are the most common side effects, occurring in at least 15% of patients.

Safety data from previous research indicates that serious issues, such as transplant rejection or new kidney problems, occurred in about 8% of patients over three years. While some side effects are common, more serious problems are less frequent.

Overall, extended-release tacrolimus is considered safe for kidney transplant recipients, but like any medication, it can have side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about extended-release tacrolimus (Envarsus XR) for kidney transplant recipients because it offers a unique dosing advantage over the standard immediate-release tacrolimus (Prograf). Unlike the immediate-release version, Envarsus XR allows for once-daily dosing, which can improve patient adherence and convenience. Additionally, Envarsus XR is designed to provide more stable blood levels of the drug, potentially reducing side effects and improving long-term outcomes for transplant patients. These features make Envarsus XR a promising option for enhancing the quality of life and health outcomes in kidney transplant recipients.

What evidence suggests that extended-release tacrolimus might be an effective treatment for kidney transplant recipients?

This trial will compare the effectiveness of extended-release tacrolimus (Envarsus XR) with immediate-release tacrolimus (Prograf) for kidney transplant recipients. Studies have shown that Envarsus XR is effective for individuals who have undergone a kidney transplant. Specifically, after one year, it had a 9% lower risk of treatment failure compared to Prograf. Over three years, only 8% of patients taking Envarsus XR experienced serious issues such as death, transplant rejection, or problems with the new kidney. This suggests that Envarsus XR not only works well but also helps maintain better kidney function over time. Research indicates that extended-release versions can provide a steadier level of the drug in the body, potentially leading to these positive outcomes. ^{1 2 4 5 6}

Who Is on the Research Team?

Leonardo V. Riella, MD, PhD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for older kidney transplant recipients who can consent, have stable kidney function and tacrolimus levels, speak English or Spanish, and are on immediate-release tacrolimus. It's not for those with severe liver disease, recent rejection episodes, advanced dementia, blindness, Parkinson's disease, very low eGFR rates (<15), intellectual disabilities, pregnancy, dual organ transplants, active cancer or uncontrolled mental health conditions.

Inclusion Criteria

Able to give informed consent for participation in the study

Patients who have regular outpatient follow-up at the Massachusetts General Hospital (MGH) transplant center

It has been over a year since my last kidney transplant.

Exclusion Criteria

My liver is not working properly.

Rejection within the last three months

History of moderate to severe dementia (defined by Dementia Severity Rating Scale ≥19)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either continue with immediate-release tacrolimus or convert to extended-release tacrolimus. Tacrolimus trough levels are monitored 3-4 weeks after conversion.

12 months

Regular visits for monitoring tacrolimus levels and neurocognitive assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including neurocognitive function and quality of life assessments.

3 months

Long-term Follow-up

Participants continue to be monitored for changes in neurocognitive function and quality of life at 12 months.

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Extended-Release Tacrolimus

Trial Overview The study compares the effects of continuing with immediate-release tacrolimus versus switching to extended-release tacrolimus on neurocognitive functions in these patients. Participants will be randomly assigned to one of the two treatment groups.

How Is the Trial Designed?

Group I: Envarsus XR conversion Experimental Treatment 1 Intervention

Patients who are randomized to this group will receive extended-release tacrolimus (Envarsus XR) at 80 percent of their total daily dose of IR tacrolimus (Prograf) before the switch. Tacrolimus trough level will be obtained 3-4 weeks after the conversion to ensure appropriate dosage.

Group II: Prograf maintenance Active Control 1 Intervention

Patients in the IR tacrolimus (Prograf) maintenance group will continue with their current dose of IR tacrolimus (Prograf) before enrollment unless the drug trough levels deviate from the therapeutic range.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Veloxis Pharmaceuticals

Industry Sponsor

Trials

43

Recruited

3,200+

Published Research Related to This Trial

Extended-release tacrolimus (tacrolimus ER) is as effective as the traditional twice-daily formulation in preventing transplant rejection in adult kidney transplant recipients, based on phase III/IV trials with follow-up up to 4 years.

Tacrolimus ER shows better renal function compared to ciclosporin and has a similar tolerability profile to the original formulation, making it a convenient once-daily option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended-release tacrolimus: a review of its use in de novo kidney transplantation. McCormack, PL.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26717860/

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

2. envarsusxr.com envarsusxr.com/hcp/efficacy-safety

Clinical Data | ENVARSUS XR® (tacrolimus extended- ... ENVARSUS XR offers lasting efficacy · At 1 year, recipients on ENVARSUS XR had a 9% lower risk of treatment failure vs those on Prograf® · At 2 years, recipients ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03266393

Envarsus XR® in Adolescent Renal Transplant Recipients It is currently unclear if Envarsus XR® would improve outcomes in adolescent organ transplant recipients.

4. envarsusxr.com envarsusxr.com/hcp/resources/convenience-case-study

Convenience Case Study De Novo kidney transplant patients: Most common adverse reactions (incidence ≥15%) reported with ENVARSUS XR are diarrhea, anemia, urinary tract infection, ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S096632742400025X

Three-year outcomes of de novo tacrolimus extended ... The conditional outcome of death, transplant rejection and/or new graft dysfunction after applying 1 year survival landmark occurred in 8% of LCPT compared to ...

6. envarsusxr.com envarsusxr.com/hcp/resources/consistency-case-study

Consistency Case Study | ENVARSUS XR® (tacrolimus ... De Novo kidney transplant patients: Most common adverse reactions (incidence ≥15%) reported with ENVARSUS XR are diarrhea, anemia, urinary tract infection, ...