Liver Immunosuppression Free Trial

NCT02498977 | Terminated Phase 4 DMC

• 2 other identifiers: ASF/001-012014-004557-14
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Transplantation, Liver

Keywords

Liver; Transplant; Immunosuppression

Outcome Measures

Primary Outcomes (1)

• 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)

  12 months from IS withdrawal

Secondary Outcomes (5)

• Proportion of tolerant participants remaining free of rejection

  3 years post IS withdrawal

• Renal function at 1, 2 and 3 years after enrollment and change in co-morbidities

  3 years post IS withdrawal

• Development of anti-HLA antibodies (before and after initiation of IS withdrawal).

  3 years post IS withdrawal

• Change in Health related quality of life (HrQOL)

  3 years post IS withdrawal

• Costs of treatment

  3 years post IS withdrawal

Study Arms (3)

Arm A (weaning)

ACTIVE COMPARATOR

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

Arm B+ (weaning- positive biomarker)

ACTIVE COMPARATOR

Participants with a positive biomarker will be weaned of immunosuppression drugs.

Genetic: Biomarker

Arm B- (maintenance)

ACTIVE COMPARATOR

Participant with negative biomarker test result will be informed of the result and will remain on baseline maintenance immunosuppression drugs.

Genetic: Biomarker

Interventions

Biomarker GENETIC

Real time polymerase chain reaction (PCR) gene expression measurement

Arm B+ (weaning- positive biomarker); Arm B- (maintenance)

Tacrolimus, cyclosporine and/or mycophenolic acid, mycophenolate mofetil or azathioprine DRUG

Immunosuppression drugs as per protocol

Also known as: IS

Arm A (weaning)

Eligibility Criteria

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

You may qualify if:

• At the time of screening: more than 3 years post-transplant if participants are ≥50 years old, OR more than 6 years post-transplant if participant age is 18-49 years old.
• Recipient of either deceased or living donor liver transplant.
• Recipient of single organ transplant only
• Liver function tests: direct bilirubin ≤17.1 umol/L and Alanine aminotransferase (ALT) ≤60 IU/L at the screening visit.
• On calcineurin inhibitor (CNI) based maintenance IS and no more than one of the following: Low dose mycophenolic acid (≤ 1080 mg daily), mycophenolate mofetil (MMF ≤ 1500 mg daily), or azathioprine (≤ 150 mg daily); or on mycophenolate/mycophenolic monotherapy (effective contraception must be used before beginning mycophenolate therapy, during therapy, and for six weeks following discontinuation of therapy).
• Ability to sign informed consent.

You may not qualify if:

• Serum positivity for Hepatitis C virus (HCV-RNA)
• Serum positivity for HIV-1 infection, Hepatitis B virus (HBV) surface antigen or HBV-DNA
• Immune-mediated liver disease in which IS discontinuation is inadvisable (autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis).
• Acute or chronic rejection within the 52 weeks prior to screening.
• Glomerular filtration rate (GFR) \<40 mL/min (to mitigate the risk of worsening renal failure should rejection occur and high level of CNI be required).
• The need for chronic anti-coagulation that cannot be safely discontinued to safely perform for a liver biopsy.
• Baseline (screening) liver biopsy showing any of the following: a) acute rejection according to Banff criteria; b) early or late chronic rejection according to Banff criteria; c) inflammatory activity and/or fibrosis in excess of permissive criteria; f) any other findings that might make participation in the trial unsafe. Eligibility will be determined by the central pathologist.
• Patient age \<18 years old at the time of transplant.
• Pregnant females and females of childbearing age not using effective contraception.
• Current illicit drug or alcohol abuse.
• Inability to participate in frequent monitoring of liver function (every 3 weeks) and clinical visits during IS withdrawal.
• Inability to comply with study directed treatment.
• Any medical condition that in the opinion of the principal investigator would interfere with safe completion of the trial.
• Participation in another clinical trial during the month prior to enrollment.

Sponsors & Collaborators

• King's College London: lead
• King's College Hospital NHS Trust: collaborator
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (2)

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

The Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle, NE7 7DN, United Kingdom

Location

MeSH Terms

Interventions

Biomarkers; Tacrolimus; Mycophenolic Acid; Azathioprine

Intervention Hierarchy (Ancestors)

Biological Factors; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Thionucleosides; Sulfur Compounds; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Alberto Sanchez-Fueyo

  King's College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2015
• First Posted: July 15, 2015
• Study Start: October 1, 2015
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: March 7, 2024

Record last verified: 2024-03

Locations

GB (2)