The study is designed to show that Certican® initiation together with reduction and thereafter discontinuation of calcineurin inhibitor (CNI) will improve significantly renal function in de novo liver transplant recipients as compared to…
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
*to show superiority of Certican®-based regimen with discontinuation of initial
CNI therapy in renal function as compared to continuation of CNI based
treatment at 11 months post randomization in liver transplant patients. This
will be evaluated by comparing renal function calculated by glomerular
filtration rate (cGFR) (Cockcroft-Gault formula) between the two groups of
patients
Secondary outcome
To assess the efficacy and safety of the two regimens, evaluated at 11 months
post randomization by the comparison between the two groups of:
*Incidence of efficacy failure (defined as the combined endpoint of Biopsy
Proven Acute Rejection, graft loss, death, lost to follow up from any reason)
*Incidence of the need for a change in the immunosuppressive regimen other than
described in the protocol
*Incidence of renal deterioration defined as a decrease > = 25% in cGFR
compared to start of randomized treatment
*Renal function after five months post randomization. Renal function is
measured as cGFR
*Incidence of treated Biopsy Proven Acute Rejection
*Patient and graft survival
*HCV replication in HCV positive patients
*Safety parameters including hypertension, diabetes mellitus (fasting glucose),
hyperlipidemia, anemia, infections and malignancies
Background summary
The success rate of liver transplantation has drastically increased over the
last 20 years. Calcineurin inhibitors (CNI) have contributed largely to the
improvement in patient and graft survival after liver transplantation. However
long-term use of CNI, cyclosporine or tacrolimus, is associated with
side-effects which are source of morbidity.
In addition to CNI therapy pretransplantation renal impairment, post operative
acute renal failure, age of recipient, hepatitis C infection, hypertension,
diabetes mellitus, hyperlipidemia can contribute to development of chronic
renal dysfunction after liver transplantation Ultimately a safe and effective
therapeutic intervention which would reduce the incidence of chronic renal
dysfunction is not available today.
Recent advances in immunosuppression, especially introduction of nonnephrotoxic
agents mycophenolate acid and sirolimus have led to evaluation of new
immunosuppressive strategies with CNI minimization or withdrawal in patients
with established renal dysfunction.
Study objective
The study is designed to show that Certican® initiation together with reduction
and thereafter discontinuation of calcineurin inhibitor (CNI) will improve
significantly renal function in de novo liver transplant recipients as compared
to continuation of CNI-based treatment.
Study design
A twelve-month, multicenter, open-label, randomized, controlled study with two
parallel groups in de novo liver transplant recipients.
Patients will be randomly assigned to one of the two treatment groups in a
ratio of 1:1.
Intervention
*Group I (comparator group):
Simulect® + CNI-based immunosuppressive regimen (cyclosporine A or tacrolimus)
according to best local practice + steroids according to best local practice.
*Group II (investigational group):
Simulect® + Certican® based immunosuppressive therapy + steroids according to
best local practice.
Study burden and risks
The study design is based on the local practice for liver transplantions. The
patiënt will have 4 additional visits on top of the standard visits according
to the local practice.
The following assessments will be done during the study:
Physical examination (2x); Vital signs and weigth (17x); blooddraw (min. 13 x);
pregnancy test when applicable(1x); liver biopsy in case of signs of acute
rejection.
Raapopseweg 1
6824 DP Arnhem
NL
Raapopseweg 1
6824 DP Arnhem
NL
Listed location countries
Age
Inclusion criteria
1. Males or females 18 - 70 years old
2. Liver transplant recipient (living or deceased donor)
3. Patients willing and capable of giving written informed consent for study participation and able to participate in the study for 12 months
4. Patients in whom an allograft biopsy will not be contraindicated
5. Females capable of becoming pregnant must have a negative pregnancy test prior to start of study and are required to practice a medically approved method of birth control for the duration of the study
6. Patients with cGFR > 50 ml/min
Exclusion criteria
1. Recipients of multiple solid organ transplants or patients that have already received a transplant in the past
2. HCV positive patients who need an active anti-viral treatment (HCV-positive patients without active antiviral treatment are allowed)
3. HIV positive patients
4. Patients who are breast feeding
5. Patients with a current severe systemic infection
6. Patients who have received an unlicensed drug or therapy within one month prior to study entry
7. Presence of any hypersensitivity to drugs similar to Certican® (e.g. macrolides)
8. Preexisting (i.e. not related to CNI-damage) renal dysfunction that, according to the judgment of the investigator, will not significantly improve after transplantation.
9. Patients that have received Simulect prior to this study.
10. Patients that have received any immunosuppressive regimen 2 months prior to this study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2005-002920-32-NL |
| CCMO | NL14298.078.06 |