A Study to Evaluate the Efficiency of Intravenously Administered Cyclosporine in de Novo Liver Transplant Recipients

Study Overview
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Brief Summary
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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.

Official Title
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A Multicenter, Open-label, Exploratory Study to Evaluate the Efficiency of Intravenously Administered Cyclosporine During the First 7 Days Post Transplant Followed by Treatment With Cyclosporine Micro Emulsion in de Novo Liver Transplant Recipients

Conditions
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Liver Transplantation

Intervention / Treatment
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* Drug: Cyclosporine (Sandimmun® i.v.)
* Drug: Cyclosporine (Sandimmun® Optoral)


Participation Criteria
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Eligibility Criteria
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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/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cyclosporine (Sandimmun®)<br>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. | Drug: Cyclosporine (Sandimmun® i.v.)<br>* 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.<br>* Other names: Sandimmun;Drug: Cyclosporine (Sandimmun® Optoral)<br>* 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.<br>* Other names: Sandimmun;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 3 or 6 months after transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver transplantation, Cyclosporine