To evaluate the long-term safety and efficacy of two concentration-controlled everolimus regimen in de novo liver transplant recipients at Month 36 post-transplantation.
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• Renal function;
• The composite efficacy endpoint of graft loss or death;
• The composite efficacy endpoint of treated biopsy proven acute rejection
(BPAR), graft loss, or death;
• The rate of progression of HCV related allograft fibrosis.
Secondary outcome
• To evaluate the efficacy endpoint of treated BPAR at Months 36 and 48
posttransplantation
• Evolution of renal function and CNI-related side effects at Months 36 and 48
posttransplantation:
• Study-/ Study-Drug related findings at Months 36 and 48 post-transplantation:
• To evaluate the premature discontinuation of study medication, and
discontinuation from the study; • To evaluate the incidence of dose
interruption and dose reduction of study medication; • To evaluate the
incidence of adverse events (AEs) and serious adverse events (SAEs); • To
evaluate the incidence of infections; • To evaluate the incidence of major
adverse cardiac events (MACE).
• Evolution of HCV and HCV related fibrosis at Months 36 and 48
post-transplantation: • To evaluate HCV viral load (HCV-RNA levels); • To
evaluate rates of progression of HCV related allograft fibrosis.
• To evaluate the rate of recurrence of hepatocellular carcinoma (HCC) at
Months 36 and 48 post-transplantation in patients with a diagnosis of HCC prior
to liver transplantation.
Background summary
The reason for this extension is to evaluate the long-term safety and efficacy
of two concentration-controlled everolimus regimen in de novo liver transplant
recipients at Month 36 post-transplantation. In addition, patients will be
receiving everolimus for up to Month 48 posttransplantation.
The most important long-term safety assessments include evaluation of renal
function, progression of HCV related allograft fibrosis, and other treatment
related effects at Month 36 posttransplantation compared to extension baseline
(Months 24 post-transplantation).
Study objective
To evaluate the long-term safety and efficacy of two concentration-controlled
everolimus regimen in de novo liver transplant recipients at Month 36
post-transplantation.
Study design
This study is an up to 24-month extension to the multicenter, open-label,
randomized, and controlled study CRAD001H2304.
All patients in the control group will be studied for 12 months (ending with
Visit 19). Patients in Groups 1 and 2 will be studied for individually variable
duration for up to 24 months. The first patients in these groups will be
studied for 24 months, the last patients only for 12 months. The end of study
will be reached, when the last patient enrolled in the extension study
completes Visit 19.
Intervention
Group 1 (elimination arm): Certican
Group 2 (minimalisation arm): low dose Prograft + Certican
Group 3 (control arm): standard treatment Prograft + steroids
Study burden and risks
The burden (number of visits and evaluations) for the patient associated with
participation in this trial does not differ from the burden when following the
standard protocol after liver transplantation. The only additional burden are
the liver biopsies 3 and 4 years post transplant (for HCV positive patients
only). There is a chance of pain and bleeding after the biopsy. However, these
risks do not differ from the risk at the routine biopsies at 1 and 2 year after
transplant, and in case of a suspected acute rejection, which are all part of
the standard treatment. Patients randomised to one of the two Certican groups
may possibly encounter the side effects of Certican (as described in the 1B
text).
Raapopseweg 1
6824 DP Arnhem
NL
Raapopseweg 1
6824 DP Arnhem
NL
Listed location countries
Age
Inclusion criteria
Completed Month 24 visit of core study and continuously being treated with assigned
regimen.
Exclusion criteria
1. Patients with clinically significant systemic infection requiring active use of IV
antibiotics at Month 24.
2. Patients who are in a critical care setting at Month 24 requiring life support measures
such as mechanical ventilation, dialysis, requirement of vasopressor agents.
3. Women of child-bearing potential, unless they meet certain criteria.
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 | EUCTR2009-017311-15-NL |
| CCMO | NL31771.078.10 |