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CompletedNCT03263052Updated Apr 22, 2020

Converting Elderly Kidney Transplant Recipients From Tacrolimus to Envarsus to Limit Neurological AE and Improve QOL

An observational study in Disorder Related to Renal Transplantation, sponsored by University of Illinois at Chicago. Completed at 1 site in United States. Open to participants aged 60 Years and older. Per ClinicalTrials.gov, last updated 2020-04-22.

Sponsored by University of Illinois at Chicago · Observational

Study type
Observational
Model
Case-crossover
Time perspective
Prospective
Enrollment
40
Ages
60 Years and older
Sex
All
01

Study summary

This study will investigate whether converting patients from FDA approved immediate-release tacrolimus to FDA approved extended release tacrolimus (Envarsus) reduces neurological side-effects, improves quality of life, and enhances adherence. A select group of elderly (> 60 years of age) patients, who are especially sensitive to tacrolimus-related adverse (AEs) effects, will be provided the opportunity to convert to Envarsus with this study.

Read the detailed description

Tacrolimus (Prograf) is a calcineurin inhibitor that is widely used in all types of solid organ transplants. However, one of the major limitations in using tacrolimus are the adverse effects that significantly reduce a transplant recipient's quality-of-life (QOL). These QOL reducing AEs associated with tacrolimus include post-transplant diabetes mellitus, neurotoxicity, diarrhea, nephrotoxicity, and alopecia. A recent open-label, multicenter, prospective phase 3b study showed that Envarsus significantly reduced tremors and improved quality of life when compared to tacrolimus. It is postulated that the mechanism behind tremor reduction occurs as a result of lower Cmax tacrolimus concentrations with the new Envarsus formulation. Given its ability for tremor improvement, it would be beneficial to investigate whether conversion from tacrolimus to Envarsus can improve other neurological AEs such as insomnia vertigo, photophobia, mood disturbances, or headache. In particular, the elderly are especially sensitive to tacrolimus-related AEs and may benefit from tacrolimus to Envarsus conversion. Further, it is useful to understand the cost effectiveness of converting to Envarsus in this patient population.

Study duration: 35 days per subject until a total of 40 subjects are enrolled. Patients will have a total of 4 visits.

02

Conditions studied

  • Disorder Related to Renal Transplantation

Keywords

  • kidney transplant
  • immunosuppression
  • tacrolimus XR
  • elderly
  • quality of life
  • neurological adverse events
03

Who can participate

Ages eligible
60 Years and older
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

This study will enroll elderly kidney transplant recipients who are at least 60 years of age and have experienced neurological adverse events while on generic tacrolimus, Prograf, or Astagraf XL.

Inclusion criteria

  1. The subject is a recipient of a living donor or deceased donor kidney only transplant
  2. Subject is > 60 years of age
  3. Subject reports neurological AEs from tacrolimus that include one or more of the following: insomnia, vertigo, photophobia, mood disturbances, tremor, and/or headache.
  4. Patients must be able to understand English and provide written informed consent
  5. Patients receiving a stable dose (i.e., no dose adjustments) of immediate-release tacrolimus (Prograf) or extended-release tacrolimus (Astagraf) for a minimum of 4-7 days at screening
  6. Patients with a screening tacrolimus trough level of 3-12 ng/mL, measured between Day -7 to 0
  7. The patient is not scheduled to begin any new medication that could interfere with tacrolimus blood levels, including prescription and over-the-counter medications, herbal or food supplements (including grapefruit and pomegranate products)
  8. Patients must be willing to commit to and comply with the schedule of study visits

Exclusion criteria

Exclusion Criteria:

  1. Multi-organ transplant
  2. Subjects not taking tacrolimus post-transplant
  3. Documented Parkinson's disease or dementia
  4. Known cause of neurological symptoms other than tacrolimus
  5. Patients with significant visual and hearing impairments affecting their ability to complete the study requirements and assessments
  6. Patients with any severe medical condition (including infection) requiring acute or chronic treatment that in the Investigator's opinion would interfere with study participation
  7. Known non-adherence (defined as documentation in the patient chart of multiple missed visits and/or medication doses) which in the investigator's opinion would interfere with the objectives of the study
  8. Patients who are taking any acute or chronic medications that may impact reaction time, memory, or sleep habits, based on Investigator discretion
  9. Patients with any form of current drug or alcohol abuse as assessed by the Investigator
04

Study design

Observational model
Case-crossover
Time perspective
Prospective
Enrollment
40 participants (actual)
Patient registry
No

Groups and cohorts

  • Tacrolimus XR

    Drug: Tacrolimus XR (Envarsus)

Interventions

  • DrugTacrolimus XR (Envarsus)

    Elderly patients (age 60 or older) on tacrolimus experiencing neurological AEs (tremor, insomnia, vertigo, photophobia, mood disturbances, or headache) presumably from tacrolimus immediate-release or tacrolimus XL will be converted to Envarsus. This conversion will be based on the Envarsus package insert which is a 20% reduction in total daily dose and is taken once a day. The conversion from Astagraf to Envarsus will be a 36% reduction.

05

What researchers measure

Primary outcomes

  1. Quality of life (QOL)

    Mean change in QOL scores from baseline to day 14 and day 28 after conversion from tacrolimus to Envarsus.

    Time frame: through study completion, an average of two years

  2. Neurological Scores

    Mean change in neurological scores (including insomnia, vertigo, photophobia, mood, headache, and tremor) from baseline to day 14 and day 28 after conversion from tacrolimus to Envarsus.

    Time frame: through study completion, an average of two years

Secondary outcomes

  1. Tacrolimus preference

    Proportion of patients preferring Envarsus compared with their previous tacrolimus formulation after 28 days of treatment

    Time frame: through study completion, an average of two years

  2. Non-adherence

    Percent of patients reporting non-adherence from baseline to day 14 and 28 after conversion from tacrolimus to Envarsus.

    Time frame: through study completion, an average of two years

  3. Incremental costs

    Mean incremental costs from baseline to day 28 following conversion to Envarsus.

    Time frame: through study completion, an average of two years

06

Study locations

1 site
  • University of Illinois at Chicago
    Chicago, Illinois 60612, United States
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03263052
Lead sponsor
University of Illinois at Chicago
Collaborators
Veloxis Pharmaceuticals
Responsible party
Patricia West-Thielke (Director of Clinical Research, University of Illinois at Chicago) — Principal investigator
First posted
Aug 28, 2017
Start date
Jul 1, 2017
Primary completion
Jan 1, 2020
Completion
Jan 1, 2020
Last update
Apr 22, 2020

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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