Kidney Transplantation
Conditions
Brief summary
The aim of the study is to evaluate the efficacy of new immunosuppressive protocol based on two applications of anti-CD52 MabCampath (Alemtuzumab) a single dose of anti-TNF-α Remicade (infliximab) monoclonal antibodies in the early posttransplant period followed by either monotherapy based on tacrolimus or sirolimus.
Interventions
DRUGMabCampath,
Primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (day 0/day 1) followed by 5 mg/kg Infliximab (day 2). For 14 days all patients received only tacrolimus, then they were randomized to either receive tacrolimus (TAC, n=13) or sirolimus (SIR, n=7) monotherapy, respectively.
DRUGRemicade
Primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (day 0/day 1) followed by 5 mg/kg Infliximab (day2). For 14 days all patients received only tacrolimus, then they were randomized to either receive tacrolimus (TAC, n=13) or sirolimus (SIR, n=7) monotherapy, respectively.
DRUGSirolimus
Primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (day 0/day 1) followed by 5 mg/kg Infliximab (day 2). For 14 days all patients received only tacrolimus, then they were randomized to either receive tacrolimus (TAC, n=13) or sirolimus (SIR, n=7) monotherapy, respectively.
DRUGTacrolimus
Primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (day 0/day 1) followed by 5 mg/kg Infliximab (day 2). For 14 days all patients received only tacrolimus, then they were randomized to either receive tacrolimus (TAC, n=13) or sirolimus (SIR, n=7) monotherapy, respectively.
Sponsors
Charite University, Berlin, Germany
Miltenyi Biomedicine GmbH
Institute for Clinical and Experimental Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* First deceased-donor kidney transplantation * Age \>18 years * Donor \<65 years * Cytomegalovirus (CMV)/ Epstein-Barr virus (EBV) seropositivity * panel reactive antibodies (PRA) \<10% * Written consent
Exclusion criteria
* Retransplantation, combined transplantation * Prior immunosuppression less than 6 months prior transplantation * Induction therapy with antibodies * Leukopenia \< 4000, thrombocytopenia \< 100 000, Haemoglobin \< 80 g/l * History of antithymoglobulin (ATG) or anti-cluster of differentiation 3 (CD3) monoclonals or anti-TNF-α * Tuberculosis history * Anti-hepatitis C virus (HCV) positivity, HBsAg * HIV positivity * Malignancy history * Allergy to study medication * Fertile women without contraception * Pregnancy, breastfeeding mothers
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Patients Alive | 1 year |
| Number of Patients With Functional Graft | 1 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kidney Graft Function (Measured by Serum Creatinine) | 1 year | Kidney graft function is measured as serum creatinine in umol/l at 1 year after transplantation. Higher levels of creatinine represents worse graft function. |
| Number of Bioptically Verified Rejection Episodes | 1 year | We calculated the number of participants with biopsy-proven subclinical rejection (based on Banff classification) within 1 year post-transplantation. |
| Presence of Subclinical Rejection in Protocol Biopsy at 12 Months (Based on Histological Examination Using Banff Classification) | 1 year | — |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sirolimus Patients received two applications of anti-CD52 MabCampath (Alemtuzumab), a single dose of anti-TNF-α Remicade (Infliximab) monoclonal antibodies in the early posttransplant period. First 14 days patients received tacrolimus monotherapy, at post-operative day (POD) 14, they were randomized to sirolimus monotherapy.
MabCampath,: Primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (day 0/day 1) followed by 5 mg/kg Infliximab (day 2). For 14 days all patients received only tacrolimus, then they were randomized to sirolimus monotherapy. | 7 |
| Tacrolimus Patients received two applications of anti-CD52 MabCampath (Alemtuzumab), a single dose of anti-TNF-α Remicade (Infliximab) monoclonal antibodies in the early posttransplant period. First 14 days patients received tacrolimus monotherapy, at POD 14, they were randomized to tacrolimus monotherapy.
MabCampath: Primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (day 0/day 1) followed by 5 mg/kg Infliximab (day 2). For 14 days all patients received only tacrolimus, then they were randomized to tacrolimus monotherapy. | 13 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | graft loss | 1 | 0 |
Baseline characteristics
| Characteristic | Tacrolimus | Sirolimus | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 7 Participants | 19 Participants |
| Age, Continuous | 55 years | 46 years | 51 years |
| Region of Enrollment Czechia | 13 participants | 7 participants | 20 participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 8 Participants | 5 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 7 | 9 / 13 |
| serious Total, serious adverse events | 5 / 7 | 0 / 13 |
Outcome results
Primary
Number of Patients Alive
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sirolimus | Number of Patients Alive | 7 Participants |
| Tacrolimus | Number of Patients Alive | 13 Participants |
Primary
Number of Patients With Functional Graft
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sirolimus | Number of Patients With Functional Graft | 6 Participants |
| Tacrolimus | Number of Patients With Functional Graft | 13 Participants |
Secondary
Kidney Graft Function (Measured by Serum Creatinine)
Kidney graft function is measured as serum creatinine in umol/l at 1 year after transplantation. Higher levels of creatinine represents worse graft function.
Time frame: 1 year
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sirolimus | Kidney Graft Function (Measured by Serum Creatinine) | 144.4 µmol/l |
| Tacrolimus | Kidney Graft Function (Measured by Serum Creatinine) | 110 µmol/l |
Secondary
Number of Bioptically Verified Rejection Episodes
We calculated the number of participants with biopsy-proven subclinical rejection (based on Banff classification) within 1 year post-transplantation.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sirolimus | Number of Bioptically Verified Rejection Episodes | 4 Participants |
| Tacrolimus | Number of Bioptically Verified Rejection Episodes | 2 Participants |
Secondary
Presence of Subclinical Rejection in Protocol Biopsy at 12 Months (Based on Histological Examination Using Banff Classification)
Time frame: 1 year
Population: In Sirolimus arm, 12 months protocol biopsy has not been performed in 2 patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sirolimus | Presence of Subclinical Rejection in Protocol Biopsy at 12 Months (Based on Histological Examination Using Banff Classification) | 1 Participants |
| Tacrolimus | Presence of Subclinical Rejection in Protocol Biopsy at 12 Months (Based on Histological Examination Using Banff Classification) | 2 Participants |