Stable liver transplant recipients identified as non-tolerant (i.e. requiring indefinite immunosuppressive therapy) on the basis of peripheral blood transcriptional biomarkers. MedDRA version: 9.1 Level: LLT Classification code 10024716 Term: Liver transplantation
Conditions
Interventions
Trade Name: RAPAMUNE 1 mg comprimidos recubiertos
Pharmaceutical Form: Tablet
INN or Proposed INN: SIROLIMUS
Other descriptive name: SIROLIMUS
Concentration unit: mg milligram(s)
Concentration type: e
Sponsors
Hospital Clinic Barcelona
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Liver transplant recipients followed-up at Hospital Clinic Barcelona who fulfill the following criteriae: 1- Age ? 18 years and weight ? 40 kg. 2- Women with risk of pregnancy: negative pregnancy test in serum before randomization and compromise to use contraception during the duration of the study. 3- Stable liver recipients with >3 years post-transplant follow-up and with maintenance immunosuppressive therapy with a calcineurin inhibitor (either alone or in combination with steroids and/or mycophenolic acid). 4- Cockcroft-Gault glomerular filtration rate ? 40 mL/min. 5- Leucocytes >3.0 x 109/L (>3,000/mm3), platelets >75 x109/L (>75,000/mm3), tryglicerides =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1- Need to receive immunosuppressive drugs for reasons other than prevention of allograft rejection. 2- Proteinuria ? 0.8 g/día. 3- Evidences of systemic infection at the time of randomization. 4- HIV infection. 5- Hypercoagulability state, history of thrombosis of the hepatic artery or portal vein (except incidental vascular thrombosis detected at the time of transplantation). 6- Transplantation of organs other than the liver.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine if in stable liver transplant recipients identified as non-tolerant on the basis of a peripheral blood transcriptional test of operational tolerance and receiving maintenance immunosuppressive therapy with calcineurin inhibitors, the substitution of these drugs by a 6-month treatment period with rapamycin induces a modification in the tolerance-related transcriptional biomarkers.;Secondary Objective: 1- To determine if in liver recipients enrolled in the study discontinuation of calcineurin inhibitors and conversion to rapamycin treatment modifies donor-specific immune responses. 2- To determine if in liver recipients enrolled in the study discontinuation of calcineurin inhibitors and conversion to rapamycin treatment affects the frequency, phenotype and function of immunoregulatory lymphocytes. 3- To determine if in liver recipients enrolled in the study discontinuation of calcineurin inhibitors and conversion to rapamycin treatment modifies the epigenetic changes associated with the tolerant state.;Primary end point(s): Proportion of stable liver transplant recipients identified as non-tolerant on the basis of a peripheral blood transcriptional test of operational tolerance who undergo a significant change in this set of transcriptional biomarkers (indicative of a high probability of immunosuppression withdrawl success), after discontinuation of calcineurin inhibitors and administration of 6-month treatment of rapamycin. | — |
Countries
Spain
Outcome results
None listed