Kidney TransplantPhase 4NCT03713645
Dosing Strategies for de Novo Once-daily Extended Release Tacrolimus (LCPT) in Kidney Transplant Recipients
A Phase 4 study testing Tacrolimus Extended Release Oral Tablet [Envarsus] 0.13mg/kg/day initiated within post-operative day 3 after kidney transplant in people with Kidney Transplant, run by Temple University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Transplant
- What is being tested?
- Tacrolimus Extended Release Oral Tablet [Envarsus] 0.13mg/kg/day initiated within post-operative day 3 after kidney transplant
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Nov 2018to 31 Jan 2022
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Temple University Hospital
Philadelphia, Pennsylvania, 19140
About this study
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.
Read the 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)
- Conditions
- Kidney Transplant
- Being tested
- Tacrolimus Extended Release Oral Tablet [Envarsus] 0.13mg/kg/day initiated within post-operative day 3 after kidney transplant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tacrolimus Extended Release Oral Tablet [Envarsus] 0.13mg/kg/day initiated within post-operative day 3 after kidney transplantDrug
Study drug (tacrolimus extended-release) initiated at 0.13/mg/kg/day for all patients
| Study group | Role | What they receive |
|---|---|---|
| Tacrolimus extended-release 0.13mg/kg/day | Experimental | Tacrolimus extended-release is initiated within post-operative day 3 of kidney transplant Receives: Drug: Tacrolimus Extended Release Oral Tablet [Envarsus] 0.13mg/kg/day initiated within post-operative day 3 after kidney transplant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to First Therapeutic Tacrolimus Trough Concentration From Initiation of Tacrolimus Extended Release Measured in Days
Therapeutic tacrolimus trough= 8-10ng/mL
Measured: Within the first 30 days of kidney transplant
Secondary outcomes (7)
Average Estimated Glomerular Filtration Rate Within 30 Days
eGFR
Measured: 30 days
Number of Participants With no Impact of Tremor on Quality of Life
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:
- 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
- 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)
Measured: At 30 days after kidney transplant
Weight-based Tacrolimus Dose During Study Period
Weight-based tacrolimus dose during study period
Measured: 30 days
Tacrolimus Dose During Study Period
Tacrolimus dose during study period
Measured: 30 days
Tacrolimus Trough Level During Study Period
Tacrolimus trough level during study period
Measured: 30 days
Weight Based Tacrolimus Dose at Therapeutic Concentration
Weight based tacrolimus dose at therapeutic concentration
Measured: At time of therapeutic tacrolimus concentration up to 30 days
Tacrolimus Dose at Therapeutic Tacrolimus Concentration
Tacrolimus dose at therapeutic tacrolimus concentration
Measured: At time of therapeutic tacrolimus concentration up to 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2018
- Study start12 Nov 2018
- Primary completion23 May 2021
- Study completion31 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Kidney TransplantStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Temple University
- Sponsor type
- University, hospital or other
- Collaborators
- Veloxis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Adam Diamond, PharmD, Principal investigator, Temple University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03713645
- Sponsor's protocol ID
- 25286
- Status last verified
- Apr 2023
- First submitted
- 18 Oct 2018
- Last updated
- 11 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dosing Strategies for de Novo Once-daily Extended Release Tacrolimus (LCPT) in Kidney Transplant Recipients
- ClinicalTrials.gov ID
- NCT03713645
- Acronym / sponsor ID
- 25286
- Conditions
- Kidney Transplant
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Temple UniversityUniversity, hospital or other
- Collaborators
- Veloxis Pharmaceuticals
- Study start
- 12 Nov 2018 (actual)
- Primary completion
- 23 May 2021 (actual)
- Study completion
- 31 Jan 2022 (actual)
- First posted
- 22 Oct 2018 (actual)
- Results
- Posted 11 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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)
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tacrolimus extended-release 0.13mg/kg/day | Experimental | Drug: Tacrolimus Extended Release Oral Tablet [Envarsus] 0.13mg/kg/day initiated within post-operative day 3 after kidney transplantTacrolimus extended-release is initiated within post-operative day 3 of kidney transplant |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (1 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tacrolimus Extended Release Oral Tablet [Envarsus] 0.13mg/kg/day initiated within post-operative day 3 after kidney transplantStudy drug (tacrolimus extended-release) initiated at 0.13/mg/kg/day for all patients | Drug | Tacrolimus extended-release 0.13mg/kg/day |
Primary outcome
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
7 secondary outcomes
Average Estimated Glomerular Filtration Rate Within 30 Days
Time frame: 30 days
Number of Participants With no Impact of Tremor on Quality of Life
Time frame: At 30 days after kidney transplant
Weight-based Tacrolimus Dose During Study Period
Time frame: 30 days
Tacrolimus Dose During Study Period
Time frame: 30 days
Tacrolimus Trough Level During Study Period
Time frame: 30 days
Weight Based Tacrolimus Dose at Therapeutic Concentration
Time frame: At time of therapeutic tacrolimus concentration up to 30 days
Tacrolimus Dose at Therapeutic Tacrolimus Concentration
Time frame: At time of therapeutic tacrolimus concentration up to 30 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adam Diamond, PharmD principal investigator
Temple University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tacrolimus Extended Release Oral Tablet [Envarsus] 0.13mg/kg/day initiated within post-operative day 3 after kidney transplant in people with Kidney Transplant, run by Temple University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2023.