Renal Transplant Rejection, Transplants and Implants
Conditions
Brief summary
To determine how safe and effective giving Thymoglobulin before transplantation to patients who are going to be receiving kidney transplants.
Detailed description
We will evaluate the therapeutic efficacy of administering Thymoglobulin® induction pre-transplantation in renal allograft recipients. Patients receiving pre-transplant Thymoglobulin will be evaluated for acute rejection (Banff '97 criteria), survival, and safety at 6 months. Overall the use of Thymoglobulin induction pre-transplantation will be safe and effective.
Interventions
DRUGThymoglobulin
Preloading Induction with Thymoglobulin® X 4 doses given day -4, day -2, day 0, and day 2 at 1.5 mg/kg/dose + corticosteroid taper + tacrolimus + MMF
Sponsors
Genzyme, a Sanofi Company
University of Cincinnati
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. Adult living donor renal transplant recipient. 2. Patient is at least 18 years of age 3. If female and of childbearing potential, have a negative serum or urine HCG within 24 hours prior to Study Day -5 (Day of 1st Thymoglobulin dose) and must practice a medically approved method of birth control for the past 30 days prior to enrollment and agree to continue this practice during the 6 month efficacy analysis. 4. Signed informed consent.
Exclusion criteria
1. Human Leukocyte Antibody (HLA) identical living donor transplant recipient. 2. History of a positive cross-match with the donor. 3. Patients with a peak CDC PRA \> 50% or a current CDC PRA \> 25%. 4. Patients who have previously received a kidney transplant. 5. Active donor or recipient serology positive for human immunodeficiency virus (HIV), Hepatitis B virus (HBV), or Hepatitis C virus (HCV). 6. History of noncompliance. 7. History of chronic corticosteroid or immunosuppressive use except for inhaled corticosteroids to treat asthma. . 8. Multiple organ transplant recipient. 9. Patient with a urinary bladder that is absent or not functional (e.g. self catheterization) pretransplant. 10. Patient who does not agree to use effective birth control during the 6-month efficacy analysis. 11. Known contraindication to administration of rabbit antithymocyte globulin. 12. Initial screening laboratory evaluations will be done locally before renal transplantation and the following laboratory values will be exclusionary: Platelets \< 100,000/mm23 or WBC \< 3000/mm3 13. Currently abusing drugs or alcohol or, in the opinion of the investigator, is at high risk for poor compliance. 14. Patient who, in the opinion of the investigator, has significant medical or psychosocial problems or unstable disease states that would preclude participation in the study. Examples of significant problems include, but are not limited to, morbid obesity or severe cardiac disease. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite End Point of Acute Rejection, Graft Loss or Patient Death | 6 months | Proportion of Patients Meeting the Composite End Point of Acute Rejection, Graft loss or Patient death |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of Infections | Not defined |
| Need for Antilymphocyte Antibody Therapy to Treat Acute Rejection | Not defined |
| Incidence of Treatment Failures: Defined as the Percentage of Patients That do Not Remain on Initial Therapy. | Ongoing |
| Serum Creatinine | Post-operative days 1-7, 30, 90 and 6 months |
| Malignancy | Undefined |
| Severity of Biopsy-proven Rejection Using Banff 97 Criteria | Not defined |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Preloading Induction With Thymoglobulin Preloading Induction with Thymoglobulin® X 4 doses given day -4, day -2, day 0, and day 2 at 1.5 mg/kg/dose + corticosteroid taper + tacrolimus + MMF
anti-thymocyte globulin (rabbit) : Preloading Induction with Thymoglobulin® X 4 doses given day -4, day -2, day 0, and day 2 at 1.5 mg/kg/dose + corticosteroid taper + tacrolimus + MMF | 6 |
| Preloading Induction With Thymoglobulin® X 3 Doses Preloading Induction with Thymoglobulin® X 3 doses given day -4 (1.5mg/kg), day -2 (1.5mg/kg), and day 0 (3mg/kg) + corticosteroid taper + tacrolimus + MMF
anti-thymocyte globulin (rabbit) : Preloading Induction with Thymoglobulin® X 3 doses given day -4 (1.5mg/kg), day -2 (1.5mg/kg), and day 0 (3mg/kg) + corticosteroid taper + tacrolimus + MMF | 5 |
| Total | 11 |
Baseline characteristics
| Characteristic | Preloading Induction With Thymoglobulin® X 3 Doses | Preloading Induction With Thymoglobulin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 6 Participants | 11 Participants |
| Age, Continuous | 36.1 years STANDARD_DEVIATION 12.5 | 50.1 years STANDARD_DEVIATION 17.1 | 43.1 years STANDARD_DEVIATION 17.1 |
| Region of Enrollment United States | 5 participants | 6 participants | 11 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 6 | 3 / 5 |
| serious Total, serious adverse events | 2 / 6 | 3 / 5 |
Outcome results
Primary
Composite End Point of Acute Rejection, Graft Loss or Patient Death
Proportion of Patients Meeting the Composite End Point of Acute Rejection, Graft loss or Patient death
Time frame: 6 months
Population: Patients received tacrolimus (goal level 10-15 ng/mL) and mycophenolate mofetil (2gm daily) at time of transplant. Methylprednisolone (MP), acetaminophen, and diphenhydramine were given as premedication for each rATG dose (500mg MP 1st dose, 250mg MP subsequent 2 doses, 125mg MP 4th dose).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Preloading Induction With Thymoglobulin x 4 Doses | Composite End Point of Acute Rejection, Graft Loss or Patient Death | Acute rejection | 1 participants |
| Preloading Induction With Thymoglobulin x 4 Doses | Composite End Point of Acute Rejection, Graft Loss or Patient Death | Graft Loss | 0 participants |
| Preloading Induction With Thymoglobulin x 4 Doses | Composite End Point of Acute Rejection, Graft Loss or Patient Death | Patient Death | 0 participants |
| Preloading Induction With Thymoglobulin® X 3 Doses | Composite End Point of Acute Rejection, Graft Loss or Patient Death | Acute rejection | 1 participants |
| Preloading Induction With Thymoglobulin® X 3 Doses | Composite End Point of Acute Rejection, Graft Loss or Patient Death | Patient Death | 0 participants |
| Preloading Induction With Thymoglobulin® X 3 Doses | Composite End Point of Acute Rejection, Graft Loss or Patient Death | Graft Loss | 0 participants |
Secondary
Incidence of Infections
Time frame: Not defined
Secondary
Incidence of Treatment Failures: Defined as the Percentage of Patients That do Not Remain on Initial Therapy.
Time frame: Ongoing
Secondary
Malignancy
Time frame: Undefined
Secondary
Need for Antilymphocyte Antibody Therapy to Treat Acute Rejection
Time frame: Not defined
Secondary
Serum Creatinine
Time frame: Post-operative days 1-7, 30, 90 and 6 months
Secondary
Severity of Biopsy-proven Rejection Using Banff 97 Criteria
Time frame: Not defined