Kidney Transplant Infection
Conditions
Brief summary
This study was designed to compare 3 immunosuppression regimens: sirolimus and tacrolimus versus everolimus and tacrolimus versus mycophenolate and tacrolimus. The primary outcome is the incidence of cytomegalovirus infection / disease, a relevant medical need in the absence of pharmacological prophylaxis.
Interventions
DRUGSirolimus
sirolimus combined to reduced dose of tacrolimus
DRUGEverolimus
everolimus combined to reduced dose of tacrolimus
DRUGMycophenolic acid
Control arm: mycophenolate combined to regular tacrolimus
Sponsors
Hospital do Rim e Hipertensão
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Recipients, adults of the first living or deceased donor kidney transplant; 2. Patients who agreed to participate in the study and signed the informed consent form
Exclusion criteria
1. Receptors with a medical history of nephrotic syndrome or focal and segmental glomerulosclerosis confirmed as the etiology of end-stage renal disease; 2. Receptors with poor understanding about chronic kidney disease and its treatment alternatives; 3. Receptors with early history of non compliance to treatment with immunosuppressive drugs; 4. Retransplantation; 5. Multi-organ recipients; 6. Recipients with BMI\> 30 kg / m2; 7. KDPI\> 80%; 8. Cold ischemia time greater than 24 hours; 9. Receptors with a percentage of anti-HLA antibodies above 50%, either class I or Class II; 10. Women of childbearing potential who do not undertake contraceptive methods (condoms or oral contraceptives). 11. Patients receiving immunosuppressive therapy prior to transplantation, except low dose of prednisone; 12. Patients with severe uncontrolled dyslipidemia; 13. Patients who have a known contraindication for administration of any of the immunosuppressive drugs provided for in this study;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Cytomegalovirus Infection or Disease | 12 months follow up | Incidence of CMV infection/disease in three study groups (SRL, EVR anda MPS). |
Countries
Brazil
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sirolimus +Tacrolimus Patients will receive initial dose of 0,05 mg/kg BID oftacrolimus to reach blood trough concentration between 3-5 ng/mL. Initial dose of sirolimus of 3mg once a day to reach blood trough concentration between 4-8 ng/mL.
Sirolimus: sirolimus combined to reduced dose of tacrolimus | 86 |
| Everolimus +Tacrolimus Patients will receive initial dose of 0,05 mg/kg BID de tacrolimus to reach blood trough concentration between 3-5 ng/mL. Initial dose of 1.5 mg BID of everolimus to reach blood trough concentration between 4-8 ng/mL.
Everolimus: everolimus combined to reduced dose of tacrolimus | 90 |
| Mycophenolate +Tacrolimus Patients will receive initial dose of 0,1 mg/kg BID de tacrolimusto reach blood trough concentration between Fixed dose of mycophenolate (mycophenolate mofetil, 1 g BID or sodium mycophenolate, 720 mg BID).
Mycophenolic acid: Control arm: mycophenolate combined to regular tacrolimus | 90 |
| Total | 266 |
Baseline characteristics
| Characteristic | Sirolimus +Tacrolimus | Total | Mycophenolate +Tacrolimus | Everolimus +Tacrolimus |
|---|---|---|---|---|
| Age, Continuous | 43.35 years STANDARD_DEVIATION 12.4 | 44.01 years STANDARD_DEVIATION 13.18 | 44.15 years STANDARD_DEVIATION 12.32 | 44.5 years STANDARD_DEVIATION 14.76 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 32 Participants | 16 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 17 Participants | 55 Participants | 13 Participants | 25 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 61 Participants | 177 Participants | 60 Participants | 56 Participants |
| Region of Enrollment Brazil | 86 participants | 266 participants | 90 participants | 90 participants |
| Sex: Female, Male Female | 22 Participants | 74 Participants | 23 Participants | 29 Participants |
| Sex: Female, Male Male | 64 Participants | 192 Participants | 67 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 86 | 1 / 90 | 3 / 90 |
| other Total, other adverse events | 0 / 86 | 0 / 90 | 0 / 90 |
| serious Total, serious adverse events | 43 / 86 | 47 / 90 | 71 / 90 |
Outcome results
Primary
Incidence of Cytomegalovirus Infection or Disease
Incidence of CMV infection/disease in three study groups (SRL, EVR anda MPS).
Time frame: 12 months follow up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sirolimus +Tacrolimus | Incidence of Cytomegalovirus Infection or Disease | 9 Participants |
| Everolimus +Tacrolimus | Incidence of Cytomegalovirus Infection or Disease | 7 Participants |
| Mycophenolate +Tacrolimus | Incidence of Cytomegalovirus Infection or Disease | 39 Participants |