Clinical trial NCT03979365: Envarsus XR Compared to Immediate Release Tacrolimus
Official title: A Prospective, Randomized, Multicenter, Open-Label, Pilot Study to Investigate Medication Adherence & Patient Reported Symptom Occurrence & Interference w/ Daily Life Comparing Envarsus XR® & Immediate Release Tacrolimus in Adult Renal Transplant Recipients (SIMPLE)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Kidney Transplant Recipients
Keywords: tacrolimus
envarsus xr
renal transplant
kidney transplant
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: Veloxis Pharmaceuticals
First posted: 2019-06-07
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The purpose of this study is to compare once-daily tacrolimus extended-release (Envarsus XR®) to twice-daily immediate release tacrolimus to find out if people taking tacrolimus extended release (Envarsus XR®) report fewer side effects, increased medication compliance and higher scores on quality of life assessments compared to people taking twice daily tacrolimus immediate release.

Detailed description: Despite improvement in short-term graft outcomes in organ transplant, transplant patients still have to take on complex medication regimens to achieve current results. Adherence to these complex medications is an important problem in light of the potential risk of acute and chronic rejection and the associated burden of increased hospitalization, cost, and diminished quality of life that results from missed doses and poor overall drug taking. Part of the diminished quality of life is also tied to the bothersome symptoms patient feel after transplant. Most patients experience symptoms that relate to either the overall transplant immunosuppression or medication specific side effects. In the BENEFIT and BENEFIT-EXT trials, \>60% of patients reported tiredness and lack of energy as an issue. Sleep problems, mood swings, restlessness, anxiety, depression, and concentration and memory difficulties appeared in approximately 50-60% of patients. In addition to these symptoms, \>38% patients also reported numerous others side effects that have been strongly associated with calcineurin-inhibitors such as tacrolimus that include dizziness, muscle cramps, trembling hands, tingling in hands and feet, and headache.

The investigators hypothesize that the use of once-daily Envarsus XR® could decrease some transplant- and tacrolimus-related adverse symptoms and potentially lead to improvement in quality of life and medication adherence when compared to twice-daily tacrolimus. In order to assess this hypothesis, a prospective, multi-center, randomized, open-label, pilot study to investigate medication adherence and patient reported symptom occurrence and interference with daily life comparing once-daily Envarsus XR® and twice-daily immediate release tacrolimus in adult renal transplant recipients (SIMPLE) is being proposed.

Eligibility criteria: Inclusion Criteria:

* Patient is an adult (18 years of age or older).
* Patient is a recipient of a deceased or living donor kidney transplant.
* Patient is able to comply with study procedures for the entire length of the study.
* Patient has been informed about the study survey and has signed an informed consent form.

Exclusion Criteria:

* Patient is unable or unwilling to complete study patient reported outcome questionnaires.
* Patient is currently receiving azathioprine
* Patient is currently receiving an mTOR inhibitor (sirolimus, everolimus)
* Patient is currently receiving an belatacept
* Patient has received investigational immunosuppression 1 month prior to transplant or post-transplant
* Patient is in a setting where a professional care taker is responsible for dispensing subject's medication.

Primary outcomes:
measure: The primary objective of this study is to compare tacrolimus formulations (Envarsus XR® versus twice a day tacrolimus) based on the difference in mean Calcineurin Inhibitor-Related Symptoms (CIRS) severity score.
timeFrame: 12 months
Secondary outcomes:
measure: Change in calcineurin inhibitor-related symptoms as measured by a change in the Calcineurin Inhibitor-Related Symptoms (CIRC) severity score.
timeFrame: 12 months
measure: Severity of calcineurin inhibitor-related symptoms
timeFrame: 12 months
measure: Change in severity of calcineurin inhibitor-related symptoms
timeFrame: From 4 to 12 months
measure: Change in any one calcineurin inhibitor-related symptom
timeFrame: From 4 to 12 months.
measure: Change in transplant-related symptoms as measured by the difference in mean transplant-related symptoms (TRS) score.
timeFrame: 12 months post-transplant
measure: Improvement in health-related qualify of life as measured by the PROMIS-29 health profile.
timeFrame: 12 months post-transplant
measure: Change in individual transplant-related symptoms
timeFrame: 12 months post-transplant
measure: Change in overall tolerability or patient bother due to side effects
timeFrame: 12 months post-transplant
measure: Change in mean taking adherence
timeFrame: 12 months post-transplant
measure: Change in patient medication satisfaction as assessed by question 14 of the Treatment Satisfaction Questionnaire for Medication.
timeFrame: 12 months post-transplant
measure: Correlation between de novo DSA and degree of taking and timing adherence
timeFrame: 12 months post-transplant
measure: Adverse events
timeFrame: 12 months post-transplant
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Mark Stegall, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mellon L, Doyle F, Hickey A, Ward KD, de Freitas DG, McCormick PA, O'Connell O, Conlon P. Interventions for increasing immunosuppressant medication adherence in solid organ transplant recipients. Cochrane Database Syst Rev. 2022 Sep 12;9(9):CD012854. doi: 10.1002/14651858.CD012854.pub2.