Liver Transplantation
Conditions
Keywords
Liver transplantation, Cyclosporine
Brief summary
The aim of this exploratory study is to evaluate the rejection rate in patients treated with cyclosporine (CsA) preceding oral administration of cyclosporine micro emulsion in de novo liver recipients. The blood levels of CsA and CsA micro emulsion will be monitored by C-2h monitoring. In addition, this study will assess the safety of this treatment regimen.
Interventions
DRUGCyclosporine (Sandimmun® i.v.)
Cyclosporine (Sandimmun® i.v.) intravenous given 2 times daily as an infusion over four hours staring at a dose of 2 X 200 mg/day for 7 days. Dosages were adjusted based on blood levels at two hours to achieve protocol specified target levels.
DRUGCyclosporine (Sandimmun® Optoral)
Sandimmun® Optoral microemulsion oral capsule twice daily starting at an initial daily dose of 8-12 mg/kg/day. Dosages were adjusted based on blood levels at two hours to achieve protocol specified target levels.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* About to undergo a primary liver transplant (including living donor, split liver). * Expected to be capable of study participation for full 6 months post-transplantation. * Allograft biopsies will be possible.
Exclusion criteria
* The surgery is a multi-organ transplant. * The patient has previously been transplanted with any other organ. * The graft derives from a non-heart beating donor. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Biopsy Proven Acute Rejection During the First 3 Months Post de Novo Liver Transplantation | 3 months | Number of patients with biopsy proven acute rejection (BPAR) within 3 months after post de novo liver transplantation. In all suspected rejection episodes an allograft biopsy was performed within a 48 hour period of initiation of an anti-rejection therapy. A designated pathologist graded the biopsies according to the Banff criteria into mild, moderate or severe BPAR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | 3 or 6 months after transplantation | The secondary efficacy endpoints included: the incidence of BPAR at 6 months; the incidence of treated acute rejection (TAR) / steroid-resistant acute rejection at 3 and 6 months; the incidence of BPAR with moderate/severe histological grading at 3 and 6 months; time to the first BPAR, the first TAR / steroid-resistant acute rejection and BPAR with moderate/severe histological grading; patient death at 3 and 6 months; and graft loss at 3 and 6 months. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cyclosporine (Sandimmun®) Period 1: Cyclosporine (Sandimmun® i.v.) intravenous given 2 times daily as an infusion over four hours staring at a dose of 2 X 200 mg/day for 7 days followed by Period 2: Sandimmun® Optoral microemulsion oral capsule twice daily starting at an initial daily dose of 8-12 mg/kg/day. Dosages were adjusted based on blood levels at two hours to achieve protocol specified target levels. | 34 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Abnormal Lab Value | 1 |
| Overall Study | Adverse Event | 5 |
| Overall Study | Death | 3 |
| Overall Study | Graft Loss | 2 |
| Overall Study | no longer requires study drug | 1 |
| Overall Study | Unsatisfactory therapeutic effect | 4 |
Baseline characteristics
| Characteristic | Cyclosporine (Sandimmun®) |
|---|---|
| Age Continuous | 53.2 years STANDARD_DEVIATION 9.6 |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 34 / 34 | 29 / 29 |
| serious Total, serious adverse events | 18 / 34 | 14 / 29 |
Outcome results
Primary
Incidence of Biopsy Proven Acute Rejection During the First 3 Months Post de Novo Liver Transplantation
Number of patients with biopsy proven acute rejection (BPAR) within 3 months after post de novo liver transplantation. In all suspected rejection episodes an allograft biopsy was performed within a 48 hour period of initiation of an anti-rejection therapy. A designated pathologist graded the biopsies according to the Banff criteria into mild, moderate or severe BPAR.
Time frame: 3 months
Population: Intention to treat (ITT) population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cyclosporine (Sandimmun®) | Incidence of Biopsy Proven Acute Rejection During the First 3 Months Post de Novo Liver Transplantation | patients with BPAR within 3 months after Tx : YES | 8 Participants |
| Cyclosporine (Sandimmun®) | Incidence of Biopsy Proven Acute Rejection During the First 3 Months Post de Novo Liver Transplantation | patients with BPAR within 3 months after Tx : NO | 26 Participants |
Secondary
Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation
The secondary efficacy endpoints included: the incidence of BPAR at 6 months; the incidence of treated acute rejection (TAR) / steroid-resistant acute rejection at 3 and 6 months; the incidence of BPAR with moderate/severe histological grading at 3 and 6 months; time to the first BPAR, the first TAR / steroid-resistant acute rejection and BPAR with moderate/severe histological grading; patient death at 3 and 6 months; and graft loss at 3 and 6 months.
Time frame: 3 or 6 months after transplantation
Population: Intention-to-treat (ITT) population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cyclosporine (Sandimmun®) | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | Patients with BPAR : YES | NA Participants |
| Cyclosporine (Sandimmun®) | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | Patients with BPAR : NO | NA Participants |
| Cyclosporine (Sandimmun®) | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | Patients with TAR : YES | 7 Participants |
| Cyclosporine (Sandimmun®) | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | Patients with TAR : NO | 27 Participants |
| Cyclosporine (Sandimmun®) | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | Patients w/ steroid-resistant acute rejection:YES | 2 Participants |
| Cyclosporine (Sandimmun®) | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | Patients w/ steroid-resistant acute rejection:NO | 32 Participants |
| Cyclosporine (Sandimmun®) | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | BPAR w/ moderate/severe histological grading:YES | 4 Participants |
| Cyclosporine (Sandimmun®) | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | BPAR w/ moderate/severe histological grading:NO | 30 Participants |
| Cyclosporine (Sandimmun®) | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | Occurence of Death : YES | 3 Participants |
| Cyclosporine (Sandimmun®) | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | Occurence of Death : NO | 31 Participants |
| Cyclosporine (Sandimmun®) | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | Occurence of Graft loss : YES | 3 Participants |
| Cyclosporine (Sandimmun®) | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | Occurence of Graft loss : NO | 31 Participants |
| 6 Months After Transplantation | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | Occurence of Graft loss : YES | 3 Participants |
| 6 Months After Transplantation | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | Patients with BPAR : YES | 10 Participants |
| 6 Months After Transplantation | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | BPAR w/ moderate/severe histological grading:YES | 4 Participants |
| 6 Months After Transplantation | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | Patients with BPAR : NO | 24 Participants |
| 6 Months After Transplantation | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | Occurence of Death : NO | 31 Participants |
| 6 Months After Transplantation | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | Patients with TAR : YES | 8 Participants |
| 6 Months After Transplantation | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | BPAR w/ moderate/severe histological grading:NO | 30 Participants |
| 6 Months After Transplantation | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | Patients with TAR : NO | 26 Participants |
| 6 Months After Transplantation | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | Occurence of Graft loss : NO | 31 Participants |
| 6 Months After Transplantation | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | Patients w/ steroid-resistant acute rejection:YES | 3 Participants |
| 6 Months After Transplantation | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | Occurence of Death : YES | 3 Participants |
| 6 Months After Transplantation | Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation | Patients w/ steroid-resistant acute rejection:NO | 31 Participants |