Liver TransplantationPhase 4LCP-TACNCT05089604
Tacrolimus Associated Tremors in Liver Transplantation: Immediate-Release Versus Extended-Release Formulations
A Phase 4 study testing Tacrolimus, Immediate Release, Oral and Tacrolimus Extended Release Oral Tablet in people with Liver Transplantation and Immunosuppression, run by University of British Columbia at 1 site in Canada.
Trial summary
This is a randomized open label study in de novo liver transplant recipients that aims to compare the risk of tacrolimus induced tremors with once daily extended-release formulation, Envarsus, versus the twice daily immediate-release formulation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Transplantation, Immunosuppression, Neurotoxicity
- What is being tested?
- Tacrolimus, Immediate Release, Oral and Tacrolimus Extended Release Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 124 participants
- Where
- 1 siteCanada
- Study dates
- 9 Jan 2023to 31 Dec 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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
- Adults aged 18 years or older
- Recipients of a first-time liver transplant
- eGFR more than 30 ml/min on the day of tacrolimus initiation
- All patients who are eligible to initiate Tacrolimus within 7 days post-liver transplant
- Informed consent
Who cannot join
- Recipients of prior organ transplant
- Need for hemodialysis either prior or following liver transplantation
- Recipients of living donor liver or split deceased donor liver allografts
- Recipients of combined liver/kidney transplants
- Recipients receiving liver allografts from donors with HCV viremia (detected through nucleic acid testing or other means)
- Patients with a history of tremor prior to transplantation including essential tremors, Parkinson's or Parkinsonian syndromes
- Patients receiving concomitant medications known to induce tremors such as dopamine blocking agents
- Baseline TSH, T3, T4 indicating hyperthyroidism
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Vancouver General Hospital
Vancouver, British Columbia, V5Z 1M9
Trana Hussaini, 6043284930, trana.hussaini@vch.ca
Jo-Ann Ford, jo-ann.ford@vch.ca
About this study
Official title: Tacrolimus Associated Tremors in Liver Transplant Recipients: a Randomized Open Label Trial Comparing De Novo Extended-release Once Daily (LCP-TAC) and Twice Daily Immediate-release (IR-TAC) Tacrolimus Formulations
This is a randomized open label study in de novo liver transplant recipients that aims to compare the risk of tacrolimus induced tremors with once daily extended-release formulation, Envarsus, versus the twice daily immediate-release formulation. Both formulations of tacrolimus are currently approved for the prevention of rejection in liver transplant patients.
Read the detailed description
Purpose: This study is designed to evaluate the incidence and severity of tremors with two different tacrolimus formulations (LCPT versus IR-TAC) when administered in combination with mycophenolate and short term corticosteroids in de novo liver transplant (LT) recipients.
Hypothesis: In de novo liver transplant recipients, an LCPT-based immunosuppression regimen, in combination with mycophenolate and short term steroids offers improved neurotoxicity profile as evidenced by lower incidence and severity of tremors and treatment discontinuation when compared to an identical regimen using twice-daily immediate-release tacrolimus.
Rationale: Tacrolimus is the first line immunosuppressive agent in all organ transplantation and its use is associated with improved patient and graft outcomes. Neurotoxicity including headaches and tremors are amongst common dose limiting toxicities associated with tacrolimus early after liver transplantation. Mitigation strategies include dosage reduction or switch to CSA, both of which can put patient at risk of rejection and other toxicities. LCPT is a new extended release formulation with improved PK parameters and evidence of improved tolerability (lower risk of tremors) in renal transplant population. In this study, we will compare the incidence and severity of tremors associated with IR-TAC, which is currently standard of care at our institution, with LCPT, which is a new dosage form added to the hospital formulary. We will be using wearable sensors to assess the severity of tremors. Furthermore, the objective and systematic documentation of tremor severity during the first 8 weeks after transplantation will provide granular data that will elucidate the natural history of tacrolimus induced tremors early post liver transplantation.
Research design: This is a single centre, prospective, randomized, open label, parallel group trial in adult de novo liver transplant recipients. Patients will be randomized (1:1) to either LCPT or IR-TAC, both groups will receive mycophenolate and short term steroids according to the standard of care protocol. This is a superiority study.
- Conditions
- Liver Transplantation, Immunosuppression, Neurotoxicity, Tremor, Tacrolimus
- Being tested
- Tacrolimus, Immediate Release, Oral, Tacrolimus Extended Release Oral Tablet
- Keywords
- Liver Transplant, Tacrolimus, Immunosuppression, Tremor, Envarsus, LCP-TAC, Neurotoxicity
- Medical subject headings
- Neurotoxicity Syndromes, Tremor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tacrolimus, Immediate Release, OralDrug
Also called Tacrolimus, Sandoz, Prograf
Twice Daily Tacrolimus
Tacrolimus Extended Release Oral TabletDrug
Also called Envarsus
Once Daily Tacrolimus
| Study group | Role | What they receive |
|---|---|---|
| LCPT | Experimental | Not described Receives: Drug: Tacrolimus Extended Release Oral Tablet |
| IR-TAC | Active comparator | Not described Receives: Drug: Tacrolimus, Immediate Release, Oral |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with tacrolimus induced tremors or worsening tremors or tacrolimus discontinuation due to neurotoxicity at 8 weeks post transplantation
Composite end point of proportion of patients with new tremor as defined by Kinesia One average score of 1 or greater or an increase from baseline of greater than or equal to 1 point at week 8 after transplantation, or tacrolimus discontinuation due to neurotoxicity (tremor, headaches, seizure or dysarthria).
Measured: 8 weeks post transplantation
Secondary outcomes (4)
Proportion of patients reaching the composite end point of death, graft loss or biopsy proven acute cellular rejection (BPAR) at 12 months post transplantation
The proportion of patients reaching the composite end point of death, graft loss or biopsy proven acute cellular rejection (BPAR)
Measured: 12 months post transplantation
Tremor related quality of life satisfaction as assessed by the Quality of Life in Essential Tremor (QUEST) scale
The Quality of Life in Essential Tremor (QUEST) is a 30 item scale rated on five-point scale (0-4), corresponding to the frequency (never, rarely, sometimes, frequently, always) with scores ranging from 0 to 120. Higher scores indicate greater dissatisfaction or disability.
Measured: 8 weeks post transplantation
Immunosuppression medication adherence as assessed by the Simplified Medication Adherence Questionnaire (SMAQ) at 8 weeks after transplant
Simplified Medication Adherence Questionnaire (SMAQ) consists of six questions evaluating different aspects of patient adherence, such as forgetfulness, routine and adverse events. SMAQ is a self-reported questionnaire that has been validated in transplant population. Patients are considered adherent if they reply to all questions with an adherent answer in all six SMAQ items. (ie 1-"yes" , 2-4 - "no", not having missed more than 2 doses during last week or having failed to take the medication on not more than 2 days during the last 3 months.
We are measuring SMAQ twice for this study (at 8 weeks and again at 12 months). Based on the literature, transplant patients are more likely to be adherent early after transplantation but they become progressively less adherent with time after transplant. We would like to determine if once daily tacrolimus has any impact on adherence.
Measured: 8 weeks post transplant
Immunosuppression medication adherence as assessed by the Simplified Medication Adherence Questionnaire (SMAQ) at 12 months after transplant
Simplified Medication Adherence Questionnaire (SMAQ) consists of six questions evaluating different aspects of patient adherence, such as forgetfulness, routine and adverse events. SMAQ is a self-reported questionnaire that has been validated in transplant population. Patients are considered adherent if they reply to all questions with an adherent answer in all six SMAQ items. (ie 1-"yes" , 2-4 - "no", not having missed more than 2 doses during last week or having failed to take the medication on not more than 2 days during the last 3 months.
We are measuring SMAQ twice for this study (at 8 weeks and again at 12 months). Based on the literature, transplant patients are more likely to be adherent early after transplantation but they become progressively less adherent with time after transplant. We would like to determine if once daily tacrolimus has any impact on adherence.
Measured: 12 months post transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2021
- Study start9 Jan 2023
- Primary completion1 Jan 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver TransplantationStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 124 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Collaborators
- Paladin Labs Inc.
- Responsible party
- Principal investigator, Trana Hussaini, University of British Columbia
- Investigators
- Trana Hussaini, Pharm D, Principal investigator, University of British ColumbiaJo-Ann Ford, RN, Study chair, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05089604
- Sponsor's protocol ID
- H20-01688
- Acronym
- LCP-TAC
- Status last verified
- Dec 2023
- First submitted
- 8 Oct 2021
- Last updated
- 2 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tacrolimus Associated Tremors in Liver Transplant Recipients: a Randomized Open Label Trial Comparing De Novo Extended-release Once Daily (LCP-TAC) and Twice Daily Immediate-release (IR-TAC) Tacrolimus Formulations
- ClinicalTrials.gov ID
- NCT05089604
- Acronym / sponsor ID
- LCP-TAC / H20-01688
- Conditions
- Liver Transplantation, Immunosuppression, Neurotoxicity, Tremor, Tacrolimus
- Keywords
- Liver Transplant, Tacrolimus, Immunosuppression, Tremor, Envarsus, LCP-TAC, Neurotoxicity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 124 participants (estimated)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Collaborators
- Paladin Labs Inc.
- Study start
- 9 Jan 2023 (actual)
- Primary completion
- 1 Jan 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 22 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized open label study in de novo liver transplant recipients that aims to compare the risk of tacrolimus induced tremors with once daily extended-release formulation, Envarsus, versus the twice daily immediate-release formulation. Both formulations of tacrolimus are currently approved for the prevention of rejection in liver transplant patients.
Detailed description
Purpose: This study is designed to evaluate the incidence and severity of tremors with two different tacrolimus formulations (LCPT versus IR-TAC) when administered in combination with mycophenolate and short term corticosteroids in de novo liver transplant (LT) recipients.
Hypothesis: In de novo liver transplant recipients, an LCPT-based immunosuppression regimen, in combination with mycophenolate and short term steroids offers improved neurotoxicity profile as evidenced by lower incidence and severity of tremors and treatment discontinuation when compared to an identical regimen using twice-daily immediate-release tacrolimus.
Rationale: Tacrolimus is the first line immunosuppressive agent in all organ transplantation and its use is associated with improved patient and graft outcomes. Neurotoxicity including headaches and tremors are amongst common dose limiting toxicities associated with tacrolimus early after liver transplantation. Mitigation strategies include dosage reduction or switch to CSA, both of which can put patient at risk of rejection and other toxicities. LCPT is a new extended release formulation with improved PK parameters and evidence of improved tolerability (lower risk of tremors) in renal transplant population. In this study, we will compare the incidence and severity of tremors associated with IR-TAC, which is currently standard of care at our institution, with LCPT, which is a new dosage form added to the hospital formulary. We will be using wearable sensors to assess the severity of tremors. Furthermore, the objective and systematic documentation of tremor severity during the first 8 weeks after transplantation will provide granular data that will elucidate the natural history of tacrolimus induced tremors early post liver transplantation.
Research design: This is a single centre, prospective, randomized, open label, parallel group trial in adult de novo liver transplant recipients. Patients will be randomized (1:1) to either LCPT or IR-TAC, both groups will receive mycophenolate and short term steroids according to the standard of care protocol. This is a superiority study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LCPT | Experimental | Drug: Tacrolimus Extended Release Oral Tablet |
| IR-TAC | Active comparator | Drug: Tacrolimus, Immediate Release, Oral |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adults aged 18 years or older
- Recipients of a first-time liver transplant
- eGFR more than 30 ml/min on the day of tacrolimus initiation
- All patients who are eligible to initiate Tacrolimus within 7 days post-liver transplant
- Informed consent
Key exclusion criteria (8 listed)
- Recipients of prior organ transplant
- Need for hemodialysis either prior or following liver transplantation
- Recipients of living donor liver or split deceased donor liver allografts
- Recipients of combined liver/kidney transplants
- Recipients receiving liver allografts from donors with HCV viremia (detected through nucleic acid testing or other means)
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, Immediate Release, OralAlso: Tacrolimus, Sandoz, PrografTwice Daily Tacrolimus | Drug | IR-TAC |
| Tacrolimus Extended Release Oral TabletAlso: EnvarsusOnce Daily Tacrolimus | Drug | LCPT |
Primary outcome
Proportion of patients with tacrolimus induced tremors or worsening tremors or tacrolimus discontinuation due to neurotoxicity at 8 weeks post transplantation
Time frame: 8 weeks post transplantation
Composite end point of proportion of patients with new tremor as defined by Kinesia One average score of 1 or greater or an increase from baseline of greater than or equal to 1 point at week 8 after transplantation, or tacrolimus discontinuation due to neurotoxicity (tremor, headaches, seizure or dysarthria).
4 secondary outcomes
Proportion of patients reaching the composite end point of death, graft loss or biopsy proven acute cellular rejection (BPAR) at 12 months post transplantation
Time frame: 12 months post transplantation
Tremor related quality of life satisfaction as assessed by the Quality of Life in Essential Tremor (QUEST) scale
Time frame: 8 weeks post transplantation
Immunosuppression medication adherence as assessed by the Simplified Medication Adherence Questionnaire (SMAQ) at 8 weeks after transplant
Time frame: 8 weeks post transplant
Immunosuppression medication adherence as assessed by the Simplified Medication Adherence Questionnaire (SMAQ) at 12 months after transplant
Time frame: 12 months post transplantation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2024.
- Individual participant dataSharing planned: Undecided
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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.
Trana Hussaini, Pharm D principal investigator
University of British Columbia
Jo-Ann Ford, RN study chair
University of British Columbia
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, Immediate Release, Oral and Tacrolimus Extended Release Oral Tablet in people with Liver Transplantation and Immunosuppression, run by University of British Columbia at 1 site in Canada.
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 5 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 2 Jan 2024. 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 Canada. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Trana Hussaini (6043284930, trana.hussaini@vch.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with tacrolimus induced tremors or worsening tremors or tacrolimus discontinuation due to neurotoxicity at 8 weeks post transplantation (time frame: 8 weeks post transplantation). 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 2 Jan 2024.