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Dosing Strategies for de Novo Once-daily Extended Release Tacrolimus (LCPT) in Kidney Transplant Recipients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03713645
Recruitment Status : Completed
First Posted : October 22, 2018
Results First Posted : May 11, 2023
Last Update Posted : May 11, 2023
Veloxis Pharmaceuticals
Information provided by (Responsible Party):
Temple University

Brief Summary:
Outcomes after kidney transplantation have been significantly enhanced with the advances made in immunosuppressive therapies. Tacrolimus is currently marketed as an extended-release once-daily formulation dosing option for patients, decreasing pill burden and possibly decreasing adverse effects. Some transplant recipients have been shown to have higher dosage requirements. According to the literature, this can be linked to genetic disparities in the metabolism of tacrolimus.. This potential complication, where differences on specific genes alters metabolism of tacrolimus, can increase difficulty in getting to a therapeutic drug level for immunosuppresants and is one large factor that contributes to the fact that kidney transplant survival rates differ between patients. Due to the enhanced bioavailability of Meltdose formulation once-daily extended-release tacrolimus, its de novo use in recent research and practice has been shown to expedite achievement of target tacrolimus trough concentrations. De novo use of once-daily tacrolimus formulations is understudied. Through a prospective investigational study, we aim to determine the optimal strategy for de novo dosing of once-daily extended release tacrolimus (MeltDose formulation) for kidney transplant recipients at Temple University Hospital.

Condition or disease Intervention/treatment Phase
Kidney Transplant Drug: Tacrolimus Extended Release Oral Tablet [Envarsus] 0.13mg/kg/day initiated within post-operative day 3 after kidney transplant Phase 4

Detailed Description:

Patients will be identified when an organ from live or deceased donor becomes available for kidney transplant. Prior to receiving their kidney transplant, subjects will be screened for inclusion/exclusion criteria on the day of transplantation. During the pre-operative preparation for transplant, patients will be consented for surgery and consented for the study at the same time if they volunteer to be included. The transplant surgeon performing the transplant operation will be responsible for screening the patients for inclusion and exclusion criteria as well as obtaining informed consent. Patients will need to provide informed consent to be included in the study, and will receive a copy of their consent. Each potential participant will be approached by the transplant surgeon and informed of all information pertinent to the study prior to providing consent. No advertisements for recruitment will be performed and no compensation will be provided for participation.

This study is a single center prospective observational study conducted at Temple University Hospital (TUH). All participants will be consented for all procedures involved in this study. This study will utilize the QUEST questionnaire (attached) to evaluate the severity of tremors at 1 month. Data to be collected includes tacrolimus trough levels, study drug dosing, hemoglobin A1c, incidence and severity of tremors, potassium, glomerular filtration rate, and rejection episodes.

Day 0 Study drug (tacrolimus) initiated at 0.13/mg/kg/day for all patients (the day of initiation decided per transplant surgeon discretion)

Day 0-4 Inpatient laboratory parameters checked every 24 hours (serum creatinine, tacrolimus level, glomerular filtration rate, potassium, blood glucose)

Day 4-30 Outpatient laboratory parameters checked three times weekly on Monday, Wednesday, and Friday (serum creatinine, tacrolimus level, glomerular filtration rate, potassium, blood glucose)

Day 30 visit (within 5 days) Draw tacrolimus trough levels, serum creatinine, estimated glomerular filtration rate, serum potassium, and blood glucose. Complete tremor questionnaire with participant.

During or prior to Day 30 visit Oral swab performed to be analyzed for testing of metabolic enzymatic activity (This will be performed to determine ability of the patient to metabolize tacrolimus)

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Dosing Strategies for de Novo Once-daily Extended Release Tacrolimus (LCPT) in Kidney Transplant Recipients
Actual Study Start Date : November 12, 2018
Actual Primary Completion Date : May 23, 2021
Actual Study Completion Date : January 31, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Tacrolimus

Arm Intervention/treatment
Experimental: Tacrolimus extended-release 0.13mg/kg/day
Tacrolimus extended-release is initiated within post-operative day 3 of kidney transplant
Drug: Tacrolimus Extended Release Oral Tablet [Envarsus] 0.13mg/kg/day initiated within post-operative day 3 after kidney transplant
Study drug (tacrolimus extended-release) initiated at 0.13/mg/kg/day for all patients

Primary Outcome Measures :
  1. Time to First Therapeutic Tacrolimus Trough Concentration From Initiation of Tacrolimus Extended Release Measured in Days [ Time Frame: Within the first 30 days of kidney transplant ]
    Therapeutic tacrolimus trough= 8-10ng/mL

Secondary Outcome Measures :
  1. Average Estimated Glomerular Filtration Rate Within 30 Days [ Time Frame: 30 days ]

  2. Number of Participants With no Impact of Tremor on Quality of Life [ Time Frame: At 30 days after kidney transplant ]

    Assessed via QUEST questionnaire which includes a self-assessment of tremor impact on quality of life. The following areas related to impact on tremor are assessed by this scale:

    1. Patients will select the severity of tremor in each of the following body parts on a scale of (none: no tremor at any time, mild: mild tremor not causing difficulty in performing any activities, moderate: tremor causes difficulty in performing some activities, marked: tremor causes difficulty in performing most or all activities, severe: tremor prevents performing some activities).

      • Head
      • Voice
      • Right arm/hand
      • Left arm/hand
      • Right leg/foot
      • Left leg/foot
    2. Several questions will be answered relating to specific situations and the impact of tremor on those situations (scale: never/no, rarely, sometimes, frequently, always/yes, not applicable)

  3. Weight-based Tacrolimus Dose During Study Period [ Time Frame: 30 days ]
    Weight-based tacrolimus dose during study period

  4. Tacrolimus Dose During Study Period [ Time Frame: 30 days ]
    Tacrolimus dose during study period

  5. Tacrolimus Trough Level During Study Period [ Time Frame: 30 days ]
    Tacrolimus trough level during study period

  6. Weight Based Tacrolimus Dose at Therapeutic Concentration [ Time Frame: At time of therapeutic tacrolimus concentration up to 30 days ]
    Weight based tacrolimus dose at therapeutic concentration

  7. Tacrolimus Dose at Therapeutic Tacrolimus Concentration [ Time Frame: At time of therapeutic tacrolimus concentration up to 30 days ]
    Tacrolimus dose at therapeutic tacrolimus concentration

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Adult patient who is 18 years of age or older receiving a kidney transplant at the Temple University Hospital's Kidney Transplant Program who are capable of understanding consent and volunteer to take part in the study

Exclusion Criteria:

Scheduled for multiple organ transplant at enrollment Non-English speaking Pregnant women Moderate-severe hepatic impairment (Child Pugh > 10 or bilirubin > 2) Existing contraindications to tacrolimus-based products including known hypersensitivity to tacrolimus or any other component of the formulation Receiving concomitant medications known to have strong drug-drug interaction potential with tacrolimus including fluconazole, voriconazole, posaconazole, isavuconazole, itraconazole, ketoconazole, diltiazem, verapamil, metronidazole, erythromycin, clarithromycin, rifampin, rifabutin, rifapentine, phenytoin, fosphenytoin, phenobarbital, primidone, carbamazepine, St. John's Wort, efavirenz, neivrapine, etravirine, atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, ritonavir, nelfinavir, saquinavir, tipranavir, cobicistat

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03713645

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United States, Pennsylvania
Temple University Hospital
Philadelphia, Pennsylvania, United States, 19140
Sponsors and Collaborators
Temple University
Veloxis Pharmaceuticals
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Principal Investigator: Adam Diamond, PharmD Temple University Hospital
  Study Documents (Full-Text)

Documents provided by Temple University:
Study Protocol  [PDF] August 21, 2018
Statistical Analysis Plan  [PDF] August 21, 2018

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Responsible Party: Temple University Identifier: NCT03713645    
Other Study ID Numbers: 25286
First Posted: October 22, 2018    Key Record Dates
Results First Posted: May 11, 2023
Last Update Posted: May 11, 2023
Last Verified: April 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action