Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Corticosteroids · 2 trials · 2 indications
The number of participants who experienced composite efficacy failure was analyzed. Composite efficacy failure was defined as treated biopsy proven acute rejection (tBPAR), graft loss, or death. A BPAR was defined as an acute rejection confirmed by biopsy with a Rejection Activity Index (RAI) score ≥ 3. tBPAR was defined as a BPAR which was treated with anti-rejection therapy. The RAI is used to score liver biopsies with acute rejection and is composed of 3 categories (portal inflammation, bile duct inflammation damage, and venous endothelial inflammation) each scored on a scale of 0 (absent) to 3 (severe) by a trained pathologist. The total RAI score = the sum of the scores of the 3 categories and ranges from 0 to 9, with a higher score indicating greater rejection. The graft was presumed to be lost on the day the patient was newly listed for a liver graft, received a graft re-transplant, or died.
The number of participants who experienced graft loss or death was analyzed. The graft was presumed to be lost on the day the patient was newly listed for a liver graft, received a graft re-transplant, or died.
Change in renal function was assessed by the estimated Glomerular Filtration Rate (eGFR) using the abbreviated (4 variables) Modification of Diet in Renal Disease (MDRD-4) formula which was developed by the MDRD Study Group and has been validated in patients with chronic kidney disease. The MDRD-4 formula used for the eGFR calculation is: eGFR (mL/min/1.73m\^2) = 186.3\*(C\^-1.154)\*(A\^-0.203)\*G\*R, where C is the serum concentration of creatinine (mg/dL), A is age (years), G=0.742 when gender is female, otherwise G=1, R=1.21 when race is black, otherwise R=1.
Composite efficacy failure was defined as treated biopsy proven acute rejection (tBPAR), graft loss, or death. A BPAR was defined as an acute rejection confirmed by biopsy with a Rejection Activity Index (RAI) score ≥ 3. tBPAR was defined as a BPAR which was treated with anti-rejection therapy. The RAI is used to score liver biopsies with acute rejection and is composed of 3 categories (portal inflammation, bile duct inflammation damage, venous endothelial inflammation) each scored on a scale of 0 (absent) to 3 (severe) by a trained pathologist. The total RAI score = the sum of the scores of the 3 categories and ranges from 0 to 9, with a higher score indicating greater rejection. The graft was presumed to be lost on the day the patient was newly listed for a liver graft, they received a graft re-transplant, or they died. The incidence rates of composite efficacy failure were estimated with a Kaplan-Meier product-limit formula.
| Arm | Type | Description |
|---|---|---|
| Everolimus + reduced tacrolimus | EXPERIMENTAL | Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus. |
| Tacrolimus elimination | EXPERIMENTAL | Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus. |
| Tacrolimus control | ACTIVE_COMPARATOR | Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus. |
| Name | Type | Description |
|---|---|---|
| Tacrolimus (reduced tacrolimus) | DRUG | After everolimus whole blood trough levels were confirmed to be in the target range of 3-8 ng/mL, tacrolimus tapering began, achieving a target tacrolimus whole blood trough level of 3-5 ng/mL by 3 weeks after randomization, a level which was maintained for the duration of the study. |
| Everolimus (reduced tacrolimus) | DRUG | Everolimus was started within 24 hours of randomization at a dose of 1.0 mg twice a day (bid, 2 mg daily dose). The dose was adjusted to maintain everolimus trough blood levels between 3-8 ng/mL for the duration of the study. |
| Tacrolimus (tacrolimus elimination) | DRUG | After everolimus whole blood trough levels were confirmed to be in the target range of 3-8 ng/mL, tacrolimus tapering began, achieving a target tacrolimus whole blood trough level of 3-5 ng/mL by 3 weeks after randomization. Tacrolimus elimination was started beginning at Month 4. Tacrolimus was tapered after everolimus whole blood trough levels were within the target range of 6-10 ng/mL. Tacrolimus was completely eliminated by the end of Month 4. |
| Everolimus (tacrolimus elimination) | DRUG | Everolimus was started within 24 hours of randomization at a dose of 1.0 mg twice a day (bid, 2 mg daily dose). The dose was adjusted to maintain everolimus trough blood levels between 3-8 ng/mL until Month 4; beginning with Month 4, the dose was adjusted to maintain everolimus trough blood levels between 6-10 ng/mL. |
| Tacrolimus (tacrolimus control) | DRUG | Tacrolimus trough levels were targeted to be maintained at 8-12 ng/mL until Month 4. At Month 4, tacrolimus whole blood trough levels were decreased to a target trough level of 6-10 ng/mL for the remainder of the study. |
| Corticosteroids | DRUG | For patients in all groups, corticosteroids were initiated at or prior to the time of transplantation according to local practice. Corticosteroids could be used for the duration of the study but could not be eliminated before Month 6. The corticosteroids were not specified in the protocol because they were adminsitered to the participants according to local practice as part of standard of care. |
Inclusion Criteria: * Written informed consent * Ability and willingness to adhere to study regimen * Completed core study with assigned regimen; Exclusion Criteria: Patients fulfilling any of the following criteria are not eligible for inclusion in this study: * Severe hypercholesterolemia or h...
Corticosteroids are used in liver transplant recipients as part of immunosuppressive therapy to prevent organ rejection. They are being studied in combination with other agents like everolimus and tacrolimus in clinical trials for de novo liver transplant recipients and for long-term maintenance therapy.
Corticosteroids are being developed by Novartis AG, which trades under the ticker NVS. The company is conducting clinical trials to evaluate the efficacy and safety of corticosteroid-based regimens in liver transplant recipients.
Corticosteroids are in Phase 3 clinical development for liver transplantation. Two Phase 3 trials have been completed, including a study of concentration-controlled everolimus with reduced tacrolimus compared to standard tacrolimus in de novo liver transplant recipients.
Corticosteroids have been studied in two completed Phase 3 trials. NCT00622869 evaluated everolimus with reduced tacrolimus versus standard tacrolimus in 719 de novo liver transplant recipients. NCT01150097 was an extension study assessing long-term efficacy and safety in 284 liver transplant recipients.
No, Corticosteroids are a separate class of immunosuppressive drugs. In the clinical trials, they were used as part of combination regimens alongside everolimus and tacrolimus, which are also immunosuppressants but work through different mechanisms.