Tacrolimus Associated Tremors in Liver Transplantation: Immediate-Release Versus Extended-Release Formulations

NCT05089604 | Recruiting Phase 4 DMC

• 1 other identifier: H20-01688
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 1

Brief 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. Both formulations of tacrolimus are currently approved for the prevention of rejection in liver transplant patients.

Conditions

Liver Transplantation; Immunosuppression; Neurotoxicity; Tremor; Tacrolimus

Keywords

Liver Transplant; Tacrolimus; Immunosuppression; Tremor; Envarsus; LCP-TAC; Neurotoxicity

Outcome Measures

Primary Outcomes (1)

• 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).

  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

  12 months post transplantation

• Tremor related quality of life satisfaction as assessed by the Quality of Life in Essential Tremor (QUEST) scale

  8 weeks post transplantation

• Immunosuppression medication adherence as assessed by the Simplified Medication Adherence Questionnaire (SMAQ) at 8 weeks after transplant

  8 weeks post transplant

• Immunosuppression medication adherence as assessed by the Simplified Medication Adherence Questionnaire (SMAQ) at 12 months after transplant

  12 months post transplantation

Other Outcomes (6)

• Incidence of biopsy proven acute cellular rejection (BPAR)

  3, 6 and 12 months post transplantation

• Incidence and severity of AKI

  1,3 and 6 months post transplant

• eGFR (MDRD) < 45 mL/min and < 30 mL/min

  6 & 12 months after transplant

Study Arms (2)

LCPT

EXPERIMENTAL

Drug: Tacrolimus Extended Release Oral Tablet

IR-TAC

ACTIVE COMPARATOR

Drug: Tacrolimus, Immediate Release, Oral

Interventions

Tacrolimus, Immediate Release, Oral DRUG

Twice Daily Tacrolimus

Also known as: Tacrolimus, Sandoz, Prograf

IR-TAC

Tacrolimus Extended Release Oral Tablet DRUG

Once Daily Tacrolimus

Also known as: Envarsus

LCPT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of British Columbia: lead
• Paladin Labs Inc.: collaborator

Study Sites (1)

Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

RECRUITING

MeSH Terms

Conditions

Neurotoxicity Syndromes; Tremor

Interventions

Tacrolimus

Condition Hierarchy (Ancestors)

Nervous System Diseases; Poisoning; Chemically-Induced Disorders; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Trana Hussaini, Pharm D

  University of British Columbia

  PRINCIPAL INVESTIGATOR

• Jo-Ann Ford, RN

  University of British Columbia

  STUDY CHAIR

Central Study Contacts

Trana Hussaini

CONTACT

6043284930; trana.hussaini@vch.ca

Eric Yoshida, MD

CONTACT

604-872-9858; eric.yoshida@vch.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: October 8, 2021
• First Posted: October 22, 2021
• Study Start: January 9, 2023
• Primary Completion: January 1, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 2, 2024

Record last verified: 2023-12

Locations

CA (1)