A clinical trial to work out how safe it is to gradually withdraw immunosuppressive drugs in people who had a liver transplant

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 148

Inclusion Criteria

1) consented adult liver transplant recipients >3 years post-transplant if aged >50 years or =6 years post-transplant if aged 18-49 years;
2) deceased or living donor liver transplant;
3) single transplanted organ;
4) direct bilirubin =17.1 umol/L and ALT =60 IU/L;
5) on calcineurin inhibitor based immunosuppression and no more than one of the following: low dose mycophenolic acid, mycophenolate mofetil, or azathioprine; or on mycophenolic/mycophenolate monotherapy;
6) ability to sign informed consent;
7) Women without childbearing potential defined as one or more of following:
•Women at least 6 weeks after surgical sterilization by bilateral tubal ligation or bilateral oophorectomy with or without hysterectomy or with hysterectomy or uterine agenesis at the day of inclusion
•women = 55 years of age at the day of inclusion who have been postmenopausal since at least 1 year
•women < 50 years of age at the day of inclusion who have been postmenopausal since at least 1 year and who have serum FSH levels > 40 mIU/mL, as well as serum estrogen levels < 30 pg/ml or a negative estrogen test.
OR
Women of childbearing potential who have a negative hCG serum or urine pregnancy test (in case of treatment with mycophenolate or mycophenolate acid two urine or serum pregnancy tests with a sensitivity of at least 25 mIU/ml at a time lag of 8-10 days between them are necessary) and agree to meet one of the following criteria [from the time of baseline and during the study and for a period of 6 weeks (IMPs containing mycophenolate or mycophenolic acid) or 6 months (IMPs containing azathioprine) following discontinuation of therapy]:
•Correct use of reliable contraception methods according to the latest version of the summary of product characteristics (SmPC).
•True abstinence (if this is already the preferred lifestyle of the person; periodic abstinence and withdrawal are not acceptable methods of contraception)
•Sexual relationship only with female partners and/or sterile male partners (a vasectomy of the male partner is not sufficient in case of treatment with IMPs containing mycophenolate or mycophenolic acid)
Sexually active (including vasectomized) men taking mycophenolate or mycophenolate acid have to use condoms for sex during treatment and for 90 days thereafter; their partners of childbearing potential have to use highly effective contraception for the same period.
Sexually active men taking azathioprine have to use condoms for sex during treatment and for 6 months thereafter; their partners of childbearing potential have to use effective contraception for the same period.
This applies also to patients with impaired fertility due to chronic uraemia, since that usually returns to normal after transplantation.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 148
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 148

Exclusion Criteria

1) serum positivity for HCV-RNA;
2) serum positivity for HIV-1 infection, HBV surface antigen or HBV-DNA;
3) autoimmune liver disease;
4) rejection within the previous year;
5) GFR<40 ml/min;
6) need for chronic anticoagulation that cannot be safely discontinued;
7) baseline liver biopsy showing rejection, advanced fibrosis or moderate-severe inflammation;
8) age <18 years at the time of transplant;
9) pregnant females and females of childbearing age not using effective/highly effective contraception ;
10) curent illicit drug or alcohol use;
11) inability to attend frequent follow-up visits;
12) inability to comply with study directed treatment;
13) medical conditions interfering with safe completion of the trial;
14) participation in another clinical trial.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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