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

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).

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)

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.

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.

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.

Incidence of biopsy proven acute cellular rejection (BPAR)

Incidence of biopsy proven acute cellular rejection (BPAR) by Banff 97 criteria

Incidence and severity of AKI

Incidence and severity of AKI based on KDIGO classification

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

Proportion of patients with eGFR (MDRD) \< 45 mL/min and \< 30 mL/min

Change in GFR

Change in GFR from month 1 (day 28) to month 12 (day 364)