A Phase 4 interventional study of Biomarker and Tacrolimus, cyclosporine and/or mycophenolic acid, mycophenolate mofetil or azathioprine in Transplantation, Liver, sponsored by King's College London. Terminated at 2 sites in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-03-07.
Sponsored by King's College London · Phase 4, Interventional, and Health services research
LIFT is prospective randomised marker-based trial to assess the clinical utility and safety of biomarker-guided immunosuppression withdrawal in liver transplantation. 'LIFT' aims to validate a biomarker test of operational tolerance to stratify liver transplant recipients before withdrawing immunosuppressive medication. Primary objective is clinical utility and risk/benefit ratio of employing a transcriptional test of tolerance to stratify liver recipients prior to immunosuppression withdrawal. Secondary objectives are: safety of biomarker-guided immunosuppression withdrawal; health-economic and quality of life impact of biomarker-guided immunosuppression withdrawal; improvement in drug-related co-morbidities; prevalence of tolerance over time; role of donor-specific anti-human leukocyte antigen (HLA) antibodies; identify mechanisms of liver allograft tolerance. It is a prospective, multi-centre, phase IV, biomarker-strategy design trial with a randomized control group in which adult liver transplant recipients will undergo immunosuppression withdrawal. The sample size is 148 patients.
This is a prospective, multi-centre, phase IV, biomarker-strategy design trial with a randomised control group in which adult liver transplant recipients will undergo immunosuppression (IS) withdrawal. Immunosuppression drugs (IS) are: Tacrolimus, cyclosporine and/or mycophenolic acid, mycophenolate mofetil or azathioprine.
Enrolled participants will be randomised 1:1 to either: 1) Non-Biomarker-based IS weaning (Weaning-All; Arm A); or 2) Biomarker-based IS weaning (Arm B). In participants allocated to Arm A IS will be withdrawn regardless of the result of the biomarker test. Among participants allocated to Arm B, only those found to be biomarker-positive (Arm B+, i.e. potentially tolerant) will be offered IS withdrawal, while biomarker-negative participants (Arm B-, i.e. potentially non-tolerant) will remain on their baseline maintenance IS. This will allow us to demonstrate that the biomarker is a useful test to personalise IS by offering drug withdrawal only to those participants who are likely to complete the process successfully, avoiding unnecessary rejections among those who have not developed tolerance. Comparing the outcome of IS withdrawal between arms A and B+ will provide direct evidence of the clinical usefulness of the test as a function of its predictive accuracy. We have established that for the biomarker to drive safe IS withdrawal its Positive Predictive Value should be no less than 0.80, and its sensitivity at least 070. To account for centre effects, we will use stratified randomization. Furthermore, to avoid biases, participants undergoing drug withdrawal and their physicians will be blinded to the biomarker results. Participants randomized to Arm B- will know their biomarker status, and will be maintained in the study until its termination and contribute to secondary clinical outcomes and to the evaluation of the stability of the tolerance signature.
Cost and quality of life (HrQOL) assessments will be conducted alongside the trial to estimate the health-economic implications of the 2 different strategies. Furthermore, sequential biological specimens will be collected to conduct ancillary mechanistic studies. Recruitment will take place in 11 European liver transplant units (King's College Hospital, Royal Free London, Newcastle, Birmingham, Leeds, Edinburgh, Cambridge, Leuven, Hannover, Berlin and Barcelona).
King's College London is the lead sponsor of 506 studies on the registry; 125 are open to participants now.
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Exclusion Criteria:
All participants satisfying clinical criteria will be weaned off immunosuppression drugs irrespective of biomarker result.
Drug: Tacrolimus, cyclosporine and/or mycophenolic acid, mycophenolate mofetil or azathioprine
Participants with a positive biomarker will be weaned of immunosuppression drugs.
Genetic: Biomarker
Participant with negative biomarker test result will be informed of the result and will remain on baseline maintenance immunosuppression drugs.
Genetic: Biomarker
Real time polymerase chain reaction (PCR) gene expression measurement
Immunosuppression drugs as per protocol
Also known as: IS
Successful discontinuation of IS with maintenance of normal allograft status
Number of patients with successful discontinuation of IS with maintenance of normal allograft status as assessed by liver biopsy and liver tests 12 months after IS withdrawal (operational tolerance)
Time frame: 12 months from IS withdrawal
Proportion of tolerant participants remaining free of rejection
Measures of rejection in patients (incidence, severity, timing, steroid resistant rejection, chronic rejection) and to investigate if liver transplant recipients under IS become operationally tolerant over time.
Time frame: 3 years post IS withdrawal
Renal function at 1, 2 and 3 years after enrollment and change in co-morbidities
To determine the extent to which IS withdrawal improve drug-related co-morbidities associated with IS use (hypertension, cardiovascular risk profile, diabetes mellitus, hyperlipidemia, malignancy) and to explore the association between operational liver transplant tolerance, iron metabolism, immunosenescence, and specific gut microbiome profiles.
Time frame: 3 years post IS withdrawal
Development of anti-HLA antibodies (before and after initiation of IS withdrawal).
To determine if the presence of donor-specific anti-HLA antibodies influence the success of IS withdrawal, and whether IS withdrawal promotes the development of anti-HLA antibodies in liver transplant recipients.
Time frame: 3 years post IS withdrawal
Change in Health related quality of life (HrQOL)
To assess the effect of IS withdrawal on the quality of life of liver transplant recipients.
Time frame: 3 years post IS withdrawal
Costs of treatment
Measuring pharmacoeconomic impact of IS withdrawal.
Time frame: 3 years post IS withdrawal
This study is terminated, as verified in Mar 2024. You cannot join it, but the record below documents what was studied.
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King's College London