A Phase 4 interventional study of Tacrolimus Pill and Tacrolimus capsule in Prophylaxis Against Liver Transplant Rejection, sponsored by Edward Geissler. Active, not recruiting at 15 sites in Germany. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-02-15.
Sponsored by Edward Geissler · Phase 4, Interventional, and Prevention
Trial participants are randomised within 14 days after liver transplantation surgery in a 1:1 ratio to two alternative treatment arms containing either Envarsus® (test arm) or Advagraf® (comparator arm) as first-line calcineurin inhibitor within a standard-of-care immunosuppressive regimen. Tacrolimus blood trough levels and drug doses are monitored at regular intervals to assess drug bioavailability and the ease and accuracy of achieving the targeted blood concentration range. Dose-normalised trough level (concentration/dose ratio) is measured at 12 weeks post-randomisation as an estimate of tacrolimus bioavailability. It is hypothesised that treatment with Envarsus® will confer a superior (higher) C/D ratio after 12 weeks of therapy owing to the superior bioavailability of this galenic drug formulation (proprietary MeltDose® technology). To test whether an elevated C/D ratio is also associated with improved clinical outcomes, a range of other pharmacokinetic, efficacy and safety variables are evaluated at 10 study visits spanning a period of 3 years.
Edward Geissler is the lead sponsor of 2 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Participants take prolonged-release tacrolimus tablets orally once daily and additionally receive standard-of-care immunosuppressive background therapy as per routine practice.
Drug: Tacrolimus Pill
Participants take prolonged-release tacrolimus capsules orally once daily and additionally receive standard-of-care immunosuppressive background therapy as per routine practice.
Drug: Tacrolimus capsule
Envarsus® tablets dosed to achieve and maintain whole blood trough levels of tacrolimus within a patient-specific therapeutic range (interval of 3 ng/ml) that lies within a wider reference range of 3-12 ng/ml.
Also known as: Envarsus
Advagraf® capsules dosed to achieve and maintain whole blood trough levels of tacrolimus within a patient-specific therapeutic range (interval of 3 ng/ml) that lies within a wider reference range of 3-12 ng/ml.
Also known as: Advagraf
Dose-normalised blood trough level of tacrolimus (concentration/dose ratio)
To calculate C/D ratio, "concentration" is the blood trough level of tacrolimus measured in a blood sample collected immediately prior to drug dosing on the day of the 12-week trial visit and "dose" is the daily dose taken by the patient on the day prior to the visit. C/D ratio is measured as a surrogate for tacrolimus bioavailability (i.e. systemic exposure per mg of drug).
Time frame: 12 weeks post-randomisation
Number of IMP dose adjustments
Time frame: Until 12 weeks post-randomisation
Time to reach the first defined range in target trough level
Time frame: Time period measured in days, assessed at 12 weeks post-randomisation
Number of measurements above and below the first defined range in target trough level
Time frame: Time period measured in days, assessed at 12 weeks post-randomisation
Dose-normalised trough level (C/D ratio) during long-term follow-up
Time frame: 1, 2 and 3 years post-randomisation
Mean tacrolimus trough level and inter-patient variability (range) of tacrolimus trough levels
Time frame: 1, 2, 4 and 12 weeks post-randomisation
Inter-patient variability (range) of tacrolimus total daily dose
Time frame: Until 12 weeks post-randomisation
Proportion of patients with trough levels lower, within, or higher than the standard reference range
Time frame: 1, 2, 4 and 12 weeks post-randomisation
Incidence and severity of clinically-confirmed biopsy-proven acute rejection
Time frame: 12 weeks and 1, 2, 3 years post-randomisation
Incidence of graft failure (defined as necessity for re-transplantation)
Time frame: 12 weeks and 1, 2, 3 years post-randomisation
Incidence of death (for any reason)
Time frame: 12 weeks and 1, 2, 3 years post-randomisation
Treatment failure rate (composite endpoint of biopsy-proven acute rejection, graft failure or death)
Time frame: 12 weeks and 1, 2, 3 years post-randomisation
Time to treatment failure (composite endpoint of biopsy-proven acute rejection, graft failure or death) after randomisation
Time frame: 3 years post-randomisation
Incidence of acute rejections requiring treatment
Time frame: 12 weeks post-randomisation
Incidence of multiple rejection episodes
Time frame: 12 weeks post-randomisation
Change versus baseline in laboratory measures of liver function (aspartate transaminase, alanine transaminase, alkaline phosphatase, gamma-glutamyltransferase, bilirubin, albumin, cholinesterase, INR)
Time frame: 12 weeks and 1, 2, 3 years post-randomisation
Change versus baseline in laboratory measures of metabolic profile (triglycerides, HDL cholesterol, LDL cholesterol, total cholesterol, HbA1c, fasting plasma glucose)
Time frame: 12 weeks and 1, 2, 3 years post-randomisation
Change versus baseline in laboratory measures of renal function (creatinine, estimated glomerular filtration rate)
Time frame: 12 weeks and 1, 2, 3 years post-randomisation
Incidence and type of malignancies diagnosed in trial participants
Time frame: 1, 2 and 3 years post-randomisation
Incidence and type of infections (hepatitis C virus, hepatitis B virus, cytomegalovirus, Epstein-Barr virus) experienced by trial participants
Time frame: 1, 2 and 3 years post-randomisation
Degree of liver fibrosis (fibroscan or biopsy)
Time frame: 12 weeks and 1, 2, 3 years post-randomisation
Incidence, type, severity, seriousness and causality of adverse events (AEs)
Time frame: 3 years post-randomisation
Change versus baseline in heart rate
Time frame: 3 years post-randomisation
Change versus baseline in blood pressure
Time frame: 3 years post-randomisation
Change versus baseline in body weight
Time frame: 3 years post-randomisation
Incidence of de novo occurrence of tremor or vision impairments
Time frame: 3 years post-randomisation
Incidence of post-transplant diabetes mellitus and post-transplant hyperglycaemia
Time frame: 12 weeks and 1, 2, 3 years post-randomisation
Dose-normalised trough level (C/D ratio)
Time frame: 12 weeks post-transplantation
Number and doses of immunosuppressive medications (incl. other tacrolimus formulations)
Time frame: At 12 weeks and after 12 weeks (if applicable)
Recurrence of primary hepatic disease
Time frame: 3 years post-randomisation
Incidence of donor-specific antibodies
Time frame: 12 weeks and 1, 2, 3 years post-randomisation
Continuation rate
Time frame: 12 weeks post-randomisation
Incidence and time to study treatment discontinuation
Time frame: 3 years post-randomisation
Incidence of patient withdrawal from the study
Time frame: 3 years post-randomisation
Time to patient withdrawal from the study
Time frame: 3 years post-randomisation
Reason for patient withdrawal from the study
Time frame: 3 years post-randomisation
Plan to share: No
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This study is active, not recruiting, as verified in Feb 2024. You cannot join it, but the record below documents what was studied.
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Edward Geissler