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

92 Participants Needed

Trial Summary

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 data supports the effectiveness of the drug Extended-Release Tacrolimus for kidney transplant recipients?

Research shows that Extended-Release Tacrolimus, taken once daily, is as effective as the traditional twice-daily version in preventing organ rejection in kidney transplant patients. It also improves patient satisfaction and adherence to the medication schedule, which is crucial for long-term success. ^{1 2 3 4 5}

Is extended-release tacrolimus safe for kidney transplant recipients?

Extended-release tacrolimus has been generally safe for kidney transplant recipients, with studies showing similar or better safety profiles compared to the twice-daily version. However, there have been rare cases of severe colitis (inflammation of the colon) reported, so close monitoring is advised. ^{1 2 6 7 8}

How is extended-release tacrolimus different from other drugs for kidney transplant recipients?

Extended-release tacrolimus is unique because it is a once-daily formulation, unlike the conventional twice-daily version. This makes it more convenient for patients and helps avoid toxic peak levels, while still providing effective prevention of transplant rejection. ^{1 5 8 9 10}

What is the purpose of this trial?

The objective of this randomized controlled study is to assess the neurocognitive outcomes between individuals using immediate-release (IR) tacrolimus (Prograf®) and those who were converted to extended-release tacrolimus (Envarsus XR) among older kidney transplant recipients (KTRs).

Research Team

Leonardo V. Riella, MD, PhD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

A switch from conventional twice-daily tacrolimus to once-daily extended-release tacrolimus in stable kidney transplant recipients. [2022]

2. Turkey pubmed.ncbi.nlm.nih.gov

Early Use of Tacrolimus Extended-Release in a Pediatric Kidney Transplant Recipient. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Conversion From Twice-Daily to Once-Daily Tacrolimus in Stable Kidney Graft Recipients. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Prolonged-release Tacrolimus After Conversion From Immediate-release Tacrolimus in Kidney Transplantation: A Retrospective Analysis of Long-term Outcomes From the ADMIRAD Study. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

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

6. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Reduced Prolonged-release Tacrolimus Exposure in De Novo Kidney Transplantation: A Randomized, Open-label, Pilot Study in Asia-OPTIMIZE Study. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Two cases of severe de novo colitis in kidney transplant recipients after conversion to prolonged-release tacrolimus. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Two years postconversion from a prograf-based regimen to a once-daily tacrolimus extended-release formulation in stable kidney transplant recipients. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Preparation of extended release solid dispersion formulations of tacrolimus using ethylcellulose and hydroxypropylmethylcellulose by solvent evaporation method. [2017]

10. China pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of once daily prolonged-release formulation of tacrolimus in children with primary nephrotic syndrome. [2019]