iver immunosuppression free trial (LIFT), version 1

Not Applicable

Completed

• Conditions: Topic: Hepatology; Subtopic: Hepatology; Disease: All Hepatology; Digestive System

• Registration Number: ISRCTN47808000
• Lead Sponsor: King's College London

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-07-08
• Study Completion: 2021-03-31
• Last Update Posted: 17 October 2022

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 148

Inclusion Criteria

Current participant inclusion criteria as of 29/01/2019:
1. At the time of screening: more than 3 years post-transplant if participants are =50 years old, OR = 6 years post-transplant if participant age is =50 years old.
2. Recipient of either deceased or living donor liver transplant.
3. Recipient of single organ transplant only
4. Liver function tests: direct bilirubin =17.1 umol/L and ALT =60 IU/L at the screening visit.
5. On calcineurin inhibitor (CNI) IS with or without one of the following: Low dose mycophenolic acid (= 1080 mg daily), mycophenolate mofetil (MMF = 1500 mg daily), azathioprine (= 150 mg daily), sirolimus/everolimus; or on monotherapy with sirolimus/everolimus or mycophenolate/mycophenolic acid monotherapy (effective contraception must be used
before beginning mycophenolate therapy, during therapy, and for six weeks following discontinuation of therapy, see Appendix 6),
6. Ability to sign informed consent.

Previous participant inclusion criteria:
1. At the time of screening: more than 3 years post-transplant if participants are =50 years old, OR = 6 years post-transplant if participant age is 18-49 years old.
2. Recipient of either deceased or living donor liver transplant
3. Recipient of single organ transplant only
4. Liver function tests: direct bilirubin =17.1 umol/L and ALT =60 IU/L at the screening visit.
5. 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)
6. Ability to sign informed consent

Exclusion Criteria

Current participant exclusion criteria as of 29/01/2019:
1. Serum positivity for HCV-RNA
2. Serum positivity for HIV-1 infection, HBV surface antigen or HBV-DNA
3. Immune-mediated liver disease in which IS discontinuation is inadvisable (autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis).
4. Acute or chronic rejection within the 52 weeks prior to screening.
5. GFR <30 mL/min (to mitigate the risk of worsening renal failure should rejection occur and high level of CNI be required).
6. The need for chronic anti-coagulation that cannot be safely discontinued to safely perform for a liver biopsy.
7. 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 (Table 1) (25); f) any other findings that might make participation in the trial unsafe. Eligibility will be determined by the central pathologist.
8. Patient age <18 years old at the time of transplant.
9. Pregnant females and females of childbearing age not using effective contraception (See Appendix 6).
10. Current illicit drug or alcohol abuse.
11. Inability to participate in frequent monitoring of liver function (every 3 weeks) and clinical visits during IS withdrawal.
12. Inability to comply with study directed treatment.
13. Any medical condition that in the opinion of the principal investigator would interfere with safe completion of the trial.
14. Participation in another clinical trial during the month prior to enrolment.

Previous participant exclusion criteria:
1. HCV infection (defined by serum positivity for HCV-RNA)
2. Positive serology for HIV-1, hepatitis B surface antigen, or hepatitis B DNA
3. Immune-mediated liver disease in which IS discontinuation is inadvisable (autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis)
4. Acute or chronic rejection within the 52 weeks prior to screening
5. GFR <40 mL/min (to mitigate the risk of worsening renal failure should rejection occur and high level of CNI be required)
6. The need for chronic anti-coagulation that cannot be safely discontinued for a minimum of 1 week to safely perform for a liver biopsy
7. Baseline (screening) liver biopsy showing any of the following:
7.1. Acute rejection according to Banff criteria
7.2. Early or late chronic rejection according to Banff criteria
7.3. Moderate-severe fibrosis (Ishak stage 3 or more)
7.4. Chronic hepatitis (defined as predominantly mononuclear portal inflammation with or without plasma cells) with moderate/marked portal inflammation (Ishak 3 or more) or with mild/moderate interface hepatitis (Ishak 2 or more)
7.5. Perivenular necro-inflammatory activity in a majority of terminal hepatic venules
7.6. Any other findings that might make participation in the trial unsafe. Elligibility will be determined by the central pathologist
8. Pregnant females and females of ch

Study & Design

• Study Type: Interventional
• Study Design: Not specified