End Stage Renal Disease
Conditions
Brief summary
The purpose of this study is to evaluate the safety and efficacy of induction therapy with Thymoglobulin in comparison with IL2 receptor antagonists (daclizumab or basiliximab).
Detailed description
A 12 month, prospective, randomized, single center, open-label study to evaluate the safety and efficacy of Rabbit anti-thymocyte globulin versus IL2 receptor antagonists in combination with tacrolimus, corticosteroids and mycophenolate mofetil in a predominantly high risk kidney transplant population.
Interventions
1.5 mg/kg IV pre-op, day 1, day 2, day 3, day 4
DRUGDaclizumab
1.0 mg/kg pre-op and 1.0 mg/kg on Day 7
Sponsors
Genzyme, a Sanofi Company
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male and female patients between 18 and 75 years of age * Male or female patients who are primary or repeat cadaveric, living unrelated or non- Human leukocyte antigen (HLA) identical living related donor renal transplant recipients * Female patients of child bearing potential must have a negative urine or serum pregnancy test within the past 48 hours prior to study inclusion. * The patient has given written informed consent to participate in the study
Exclusion criteria
* Patient has previously received or is receiving an organ transplant other than a kidney. * Patients who are recipients of a multiple organ transplant. * Patient has received a primary or re-transplant from an HLA-identical living donor. * Any positive cross-match. * Patient is the recipient of a pediatric donor kidney from a pediatric donor aged 8 years or less. * Patient has received an ABO incompatible donor kidney. * Recipient or donor is known to be seropositive for hepatitis C virus (HCV) or B virus (HBV) except for hepatitis B surface antibody positive. * Recipient or donor is known to be seropositive for human immunodeficiency virus (HIV). * Patient has uncontrolled concomitant infection or any other unstable medical condition that could interfere with the study objectives. * Patients with thrombocytopenia (\<75,000/mm3 ), with an absolute neutrophil count of \< 1,000/mm3); and/or leucopoenia (\< 2,000/mm3), or anemia (hemoglobin \< 6 g/dL) prior to study inclusion. * Patient is taking or has been taking an investigational drug in the 30 days prior to transplant. * Patient has a known hypersensitivity to tacrolimus, mycophenolate mofetil, rabbit anti-thymocyte globulin, daclizumab or corticosteroids. * Patients with severe diarrhea or other gastrointestinal disorders that might interfere with their ability to absorb oral medication. * Patients with a history of malignancy within the last five years, except for successfully excised squamous or basal cell carcinoma of the skin. * Patient is pregnant or lactating, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by positive human Chorionic Gonadotropin (hCG) laboratory test. * Women of childbearing potential must use two reliable forms of contraception simultaneously, unless they are status post bilateral tubal ligation, bilateral oophorectomy, or hysterectomy. Effective contraception must be used before beginning study drug therapy, for the duration of the study and for 6 weeks following completion of the study. * Patient has any form of substance abuse, psychiatric disorder or a condition that, in the opinion of the investigator, may invalidate communication with the investigator. * Inability to cooperate or communicate with the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Treatment Efficacy Will be Defined as the Number of Patients With Biopsy Proven Acute Rejection at One Year Post-transplant. | One year |
Secondary
| Measure | Time frame |
|---|---|
| Graft Survival at One Year Post-transplant | One year |
| Incidence of Post-transplant Infections, Including, But Not Limited to, CMV Infection and Disease, BK Infection and Nephropathy, Other Opportunistic Infections, Urinary Tract Infections, Pneumonia, and Sepsis | one year |
| Number of Patients Requiring Antilymphocyte Therapy for Acute Rejection. | One year |
| Incidence of Leukopenia, Defined as a Total White Blood Cell Count of Less Than 2,000 Cells/mm3 | One year |
| Incidence of Thrombocytopenia, Defined as a Platelet Count of Less Than 100,000 Cells/mm3 | One year |
| Incidence of Post-transplant Malignancies, Including Post-transplant Lymphoproliferative Disease (PTLD) and Skin Cancers. | One year |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Thymoglobulin Subjects receiving Thymoglobulin as induction agent in renal transplantation
Rabbit Antithymocyte globulin: 1.5 mg/kg IV pre-op, day 1, day 2, day 3, day 4 | 102 |
| Zenapax subject who will receive daclizumab or basiliximab as induction agent in renal transplantation
Daclizumab: 1.0 mg/kg pre-op and 1.0 mg/kg on Day 7 | 98 |
| Total | 200 |
Baseline characteristics
| Characteristic | Thymoglobulin | Zenapax | Total |
|---|---|---|---|
| Age, Continuous | 52 years STANDARD_DEVIATION 13 | 49 years STANDARD_DEVIATION 14 | 50.2 years STANDARD_DEVIATION 13.5 |
| Sex: Female, Male Female | 43 Participants | 36 Participants | 79 Participants |
| Sex: Female, Male Male | 59 Participants | 62 Participants | 121 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 37 / 102 | 44 / 98 |
| serious Total, serious adverse events | 0 / 102 | 0 / 98 |
Outcome results
Primary
Treatment Efficacy Will be Defined as the Number of Patients With Biopsy Proven Acute Rejection at One Year Post-transplant.
Time frame: One year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thymoglobulin | Treatment Efficacy Will be Defined as the Number of Patients With Biopsy Proven Acute Rejection at One Year Post-transplant. | 6 participants |
| Zenapax | Treatment Efficacy Will be Defined as the Number of Patients With Biopsy Proven Acute Rejection at One Year Post-transplant. | 10 participants |
Secondary
Graft Survival at One Year Post-transplant
Time frame: One year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thymoglobulin | Graft Survival at One Year Post-transplant | 101 participants |
| Zenapax | Graft Survival at One Year Post-transplant | 95 participants |
Secondary
Incidence of Leukopenia, Defined as a Total White Blood Cell Count of Less Than 2,000 Cells/mm3
Time frame: One year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thymoglobulin | Incidence of Leukopenia, Defined as a Total White Blood Cell Count of Less Than 2,000 Cells/mm3 | 21 participants |
| Zenapax | Incidence of Leukopenia, Defined as a Total White Blood Cell Count of Less Than 2,000 Cells/mm3 | 4 participants |
Secondary
Incidence of Post-transplant Infections, Including, But Not Limited to, CMV Infection and Disease, BK Infection and Nephropathy, Other Opportunistic Infections, Urinary Tract Infections, Pneumonia, and Sepsis
Time frame: one year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thymoglobulin | Incidence of Post-transplant Infections, Including, But Not Limited to, CMV Infection and Disease, BK Infection and Nephropathy, Other Opportunistic Infections, Urinary Tract Infections, Pneumonia, and Sepsis | 52 participants |
| Zenapax | Incidence of Post-transplant Infections, Including, But Not Limited to, CMV Infection and Disease, BK Infection and Nephropathy, Other Opportunistic Infections, Urinary Tract Infections, Pneumonia, and Sepsis | 58 participants |
Secondary
Incidence of Post-transplant Malignancies, Including Post-transplant Lymphoproliferative Disease (PTLD) and Skin Cancers.
Time frame: One year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thymoglobulin | Incidence of Post-transplant Malignancies, Including Post-transplant Lymphoproliferative Disease (PTLD) and Skin Cancers. | 3 participants |
| Zenapax | Incidence of Post-transplant Malignancies, Including Post-transplant Lymphoproliferative Disease (PTLD) and Skin Cancers. | 0 participants |
Secondary
Incidence of Thrombocytopenia, Defined as a Platelet Count of Less Than 100,000 Cells/mm3
Time frame: One year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thymoglobulin | Incidence of Thrombocytopenia, Defined as a Platelet Count of Less Than 100,000 Cells/mm3 | 43 participants |
| Zenapax | Incidence of Thrombocytopenia, Defined as a Platelet Count of Less Than 100,000 Cells/mm3 | 13 participants |
Secondary
Number of Patients Requiring Antilymphocyte Therapy for Acute Rejection.
Time frame: One year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thymoglobulin | Number of Patients Requiring Antilymphocyte Therapy for Acute Rejection. | 3 Patients |
| Zenapax | Number of Patients Requiring Antilymphocyte Therapy for Acute Rejection. | 8 Patients |