Clinical trial NCT01399242: Efficacy of Certican® in Combination With Myfortic® in Renal
Official title: Efficacy and Safety of Certican® in Combination With Myfortic® in Adult Renal Allograft Recipients Following Calcineurin Inhibitor Withdrawal at Week 16 Compared to Patients Who Are Maintained on Tacrolimus and Myfortic®
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Disorder Related to Renal Transplantation
Keywords: Disorder Related to Renal Transplantation
Lead sponsor: Hospital Universitário São José
Sponsor class: OTHER
First posted: 2011-07-21
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The primary objective is to demonstrate the superiority of everolimus plus Myfortic® plus corticosteroids following CNI withdrawal at week 16 compared to tacrolimus plus Myfortic® plus corticosteroids as measured by the change in calculated Glomerular Filtration Rate (cGFR) from baseline to month 12.

The key secondary objective is to demonstrate non-inferiority of biopsy-proved acute rejection (BPAR), graft loss, death or loss to follow-up (composite endpoint) at month 12 in patients switched to everolimus plus Myfortic® plus corticosteroids following CNI withdrawal at Week 16 compared to patients maintained on tacrolimus plus Myfortic® plus corticosteroids.

Patients will be submitted to monthly GFR determination but, for group comparison, only the GFR measured at month 12 and month 24 of renal transplantation will be used.

Detailed description: 1.Forty patients will be selected at 16 weeks of renal transplantation with 20 patients allocated in each study arm. The allocation will be done randomly to provide similar epidemiological characteristics with respect to gender, age, renal function and co morbidities in the two groups. The informed consent will obtained after an interview involving the researcher and patient when the protocol will be explained.

1.1 Study protocol

Patients of renal transplant unit at the Sao Jose University Hospital who sign the inform consent and fulfill the inclusion/exclusion criteria will be enrolled in this study.

The main population will be low-risk kidney transplant recipients defined as follow: primary transplant, patients older than 18 years old and recipients of first kidney transplantation with living donor with PRA \<10%, using tacrolimus, EC-MPS, and steroids as primary immunosuppression, without delayed graft function and with stable renal function 3 months after transplantation.

Patients who fulfill the inclusion criteria and agree to participate in this study will have the CNI withdrawn and the immunosuppressive regimen will be based on everolimus.

The switch will be done as follows: patients' therapy will be replaced from CNI-based to everolimus-based immunosuppression. Everolimus will be introduced on day 1 at dose of 2 mg/day (1mg bid), and then everolimus trough levels will be obtained from day 3 onwards until C0 reaches the target for three consecutive days. Through levels will be adjusted to achieve 6-10ng/ml. Thereafter, if the target level was reached, the measurement will be performed weekly for 4 weeks and every 2 weeks until 8 weeks after conversion.

In parallel, the CNI dose will be reduced by 50% on day 1 and another 25% on day 7. The CNI will be withdrawn on day 14 if the target levels of everolimus are obtained. EC-MPS will be unchanged until day 14 after conversion, thereafter it will be decreased if necessary from 1440mg to 1080mg/day. The dose of EC-MPS will not be below 1080 mg/day.

Corticosteroids would be unchanged. A protocol renal biopsy will be performed at the end of the study, 12 months after transplantation. A per-operatory biopsy at baseline will not be performed, since this is not a routine practice of the transplant center and because the patients have a low immunological risk.

1.3- Inclusion criteria

1.3.1- Men and women between 18-70 years old 1.3.2- Receptors of a first living-donor kidney allograft 1.3.3- Patients must have been on a tacrolimus+myfortic regimen for at least 2 weeks prior to randomization

1.4- Exclusion criteria

1.4.1- Patients with evidence of any acute rejection following transplantation at the time of randomization 1.4.2- GFR ≤ 35 ml/min 1.4.3- Proteinuria \> 800 mg/day 1.4.4- Recipients of multiple organ transplants 1.4.5- Chronic hepatic failure 1.4.6- Asymptomatic bacteriuria 1.4.7- Creatinine ≥ 2mg/dL on CNI withdrawn time 1.4.8- Proteinuria ≥ 1g/24h on CNI withdrawn time 1.4.9- Presence of uncontrolled hypercholesterolemia (≥ 350 mg/dL, ≥ 9.1 mmol/L) 1.4.10- Hypertriglyceridemia (≥ 500 mg/dL, ≥ 5.6 mmol/L)

1.5- Statistical analysis

This is an investigational and interventional study, with two-arms, to evaluate the renal function and composite efficacy end-point after conversion of immunosuppressive regime from tacrolimus to everolimus. As this is a pilot study, the sample size was estimated with 20 patients in each arm (total = 40 patients) according to the number of kidney transplants usually performed at the hospital.

For GRF evaluation ANOVA will be used. A difference of 5-10ml/min at GRF is expected comparing study and control group.

The incidence of acute rejection will be analyzed by chi-square.

Eligibility criteria: Inclusion Criteria:

* Men and women between 18-70 years old
* Receptors of a first living-donor kidney allograft
* Patients must have been on a tacrolimus+myfortic regimen for at least 2 weeks prior to randomization

Exclusion Criteria:

* Patients with evidence of any acute rejection following transplantation at the time of randomization
* GFR ≤ 35 ml/min
* Proteinuria \> 800 mg/day
* Recipients of multiple organ transplants
* Chronic hepatic failure
* Asymptomatic bacteriuria
* Creatinine ≥ 2mg/dL on CNI withdrawn time
* Proteinuria ≥ 1g/24h on CNI withdrawn time
* Presence of uncontrolled hypercholesterolemia (≥ 350 mg/dL, ≥ 9.1 mmol/L)
* Hypertriglyceridemia (≥ 500 mg/dL, ≥ 5.6 mmol/L)

Primary outcomes:
measure: Glomerular Filtration Rate
timeFrame: 96 weeks
Secondary outcomes:
measure: Non-inferiority of biopsy-proved acute rejection (BPAR), graft loss, death
timeFrame: 1 year after enrollment
Other outcomes:
Locations:
city: Belo Horizonte
country: Brazil
facility: Hospital Universitário São José
state: Minas Gerais
Study officials:
affiliation: Hospital Universitário Sao José
name: Euler P lasmar
role: STUDY_DIRECTOR
References:
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