Kidney Transplantation, Kidney Disease
Conditions
Keywords
Immunosuppression, Renal Failure
Brief summary
Transplant rejection occurs when a patient's body does not recognize the new organ and attacks it. Patients who have kidney transplants must take drugs to prevent transplant rejection. Alemtuzumab is a man-made antibody used to treat certain blood disorders. The purpose of this study is to test the safety and effectiveness of using alemtuzumab in combination with two other drugs, sirolimus and tacrolimus, to prevent organ rejection after kidney transplantation. This study will also test whether this combination of medications will allow patients to eventually stop taking antirejection medications entirely. Study hypothesis: A new strategy of immunosuppression using alemtuzumab, tacrolimus, and sirolimus for human renal transplantation will permit a step-wise withdrawal from immunosuppressive drugs.
Detailed description
Drugs that suppress the immune system, such as sirolimus and tacrolimus, have contributed to increased success of transplantation. However, to prevent organ rejection, transplant recipients need to take immunosuppressive drugs for the rest of their lives, and these drugs make patients more susceptible to infection, endangering their health and survival. Regimens that are less toxic to or can eventually be withdrawn from transplant recipients are needed. Alemtuzumab is a monoclonal antibody that binds to and depletes excess T cells in the bone marrow of leukemia patients. This study will determine the effects of intravenous alemtuzumab and oral sirolimus and tacrolimus after kidney transplantation. The study will also evaluate this regimen's potential to allow eventual discontinuation of components of long-term immunosuppressive therapy. This study will last up to 4 years. Participants will undergo kidney transplantation on Day 0 and will receive intravenous doses of alemtuzumab, acetaminophen, and diphenhydramine on Days 0, 1, and 2, as well as methylprednisolone on Day 0. After transplant, patients will receive up to 10 days of valganciclovir or acyclovir. Participants will take tacrolimus daily by mouth for at least 60 days after transplant and sirolimus daily by mouth for at least 12 months after transplant. As part of opportunistic infection (OI) prophylaxis, participants will also take sulfamethoxazole-trimethoprim by mouth 3 times a week, valganciclovir or acyclovir for up to 10 days post-transplant, and clotrimazole or nystatin by mouth for at least 3 months post-transplant. There will be a minimum of 62 study visits spread out over 4 years after transplant. Vital signs measurement, adverse event and OI reporting, medication history, physical exam, and blood collection will occur at selected visits. Sirolimus withdrawal will begin when a participant meets certain study criteria. The withdrawal process will occur over a minimum of 3 months at an approximate rate of 33% of the pre-withdrawal dose per month. Participants eligible for sirolimus withdrawal will undergo several kidney biopsies, including one 2 weeks prior to the start of withdrawal, 6 and 12 months after completion of withdrawal, 1 year after study enrollment, and annually thereafter.
Interventions
DRUGAlemtuzumab
30mg intravenous infusion on days 0 (transplant), 1, and 2
DRUGSirolimus
2mg/day orally within 24-48 hrs post-transplant, and adjusted to achieve blood levels of 8-12 ng/mL for 1 year
DRUGTacrolimus
2mg orally twice daily, on days 1-60
PROCEDUREKidney transplant
Kidney transplant with primary cadaveric or non-HLA-identical living donor kidney (0-3 HLA-antigen mismatch)
DRUGMethylprednisolone (or equivalent)
250 mg intravenous infusion 60 minutes prior to first dose of alemtuzumab
DRUGAcetaminophen
650 mg may be given 30-60 minutes prior to start of each infusion of alemtuzumab to prevent infusion related side effects such as fever, skin rash and pruritis
DRUGDiphenhydramine
25 mg may be given 30-60 minutes prior to start of each infusion of alemtuzumab to prevent infusion related side effects such as fever, skin rash and pruritis
DRUGTrimethoprim (TMP)/Sulfa (Bactrim, Septra)
1 double strength tablet 3 times a week from day 1 through 1 year post-transplant.
DRUGValgancyclovir
Given orally beginning on day 1 for up to 10 days post-transplant (until participant discharged from hospital if prior to 10 days). Dose adjusted based on participants calculated creatinine clearance
DRUGAcyclovir
400 mg orally twice daily or 800 mg orally four times daily (dose adjusted based on calculated creatinine clearance and cytomegalovirus antibody serologic status of donor and recipient) for a minimum of 3 months starting when valganciclovir discontinued.
DRUGPentamidine
300 mg/6 mL inhalation therapy once monthly for a total of 6 treatments. First treatment given within one week post-transplant for participants with a known allergy or intolerance to sulfa
DRUGClotrimazole
10 mg orally four times daily for a minimum of 3 months post-transplant (subjects take either clotrimazole or nystatin, not both)
DRUGNystatin
500,000 units/5 mL orally four times daily for a minimum of 3 months post-transplant (subjects take either nystatin or clotrimazole, not both)
Sponsors
Immune Tolerance Network (ITN)
University of Wisconsin, Madison
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Kidney transplant with primary cadaveric or non-Human Leukocyte Antigen (HLA)-identical living donor kidney (0-3 HLA-antigen mismatch) * Receiving only a kidney and no other organs * Able to take medications by mouth * Willing to use acceptable methods of contraception
Exclusion criteria
* Received HLA-identical living-donor kidney transplant * HLA-antigen mismatch greater than 3 * Panel reactive antibody (PRA) value greater than 10% at any time prior to enrollment * Received a non-heart-beating donor allograft * Received a kidney from a donor who is greater than 60 years of age * End-stage Renal Disease (ESRD) due to Focal Segmental Glomulerosclerosis (FSGS) * Previous kidney transplant * Received multiorgan transplant * Concomitant systemic corticosteroid therapy for other medical diseases * Known hypersensitivity to alemtuzumab, tacrolimus, methylprednisolone, or sirolimus * Human Immunodeficiency Virus (HIV) infected * Hepatitis C virus infected * Positive for hepatitis B surface antigen * Received dual or en-bloc pediatric kidneys * Anti-human Globulin (AHG) or T cell crossmatch positive * Investigational drug within 6 weeks of study entry * Known clinically significant cardiovascular or cerebrovascular disease * Previous or current history of cancer or lymphoma. Patients with adequately treated basal or squamous cell skin carcinoma are not excluded. * Clinically significant coagulopathy or a requirement for chronic anti-coagulation therapy precluding biopsy * Cytomegalovirus (CMV)-negative recipient, if received kidney is from a CMV-positive donor * History of a psychological illness or condition that, in the opinion of the investigator, may interfere with the study * Graves disease. Patients who have been previously adequately treated with radioiodine ablative therapy are not excluded. * Active systemic infections * Platelets less than 100,000 cells/mm\^3 at study entry * Pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Acute Rejections in All Enrolled Participants | Four years post-transplant | Number of acute rejections\[1\] in all enrolled subjects from the time of transplantation to the end of the trial (four years post-transplant) 1. Acute rejection is defined as a biopsy-proven rejection: a renal biopsy demonstrates acute cellular or humoral rejection of Banff\[2\] Grade 1B or greater; or presumed rejection in the absence of biopsy-proven rejection, the participant is treated for an unexplained 20% increase in serum creatinine. 2. Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Acute Rejections Between Initiation of Sirolimus Withdrawal and End of Study | Initiation of sirolimus to end of study (up to four years post-transplant) | Acute rejections\[1\] between initiation of sirolimus withdrawal and end of study 1\] Acute rejection is defined as a biopsy-proven rejection: a renal biopsy demonstrates acute cellular or humoral rejection of Banff\[2\] Grade 1B or greater; or presumed rejection in the absence of biopsy-proven rejection, the participant is treated for an unexplained 20% increase in serum creatinine. \[2\] Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999 |
| Time From Transplantation to Acute Rejection in Participants for Whom Sirolimus Withdrawal Was Not Initiated | Transplantation to acute rejection (up to four years post-transplantation) | Time (days) to acute rejection\[1\] for participants where sirolimus was not initiated 1\] Acute rejection is defined as a biopsy-proven rejection: a renal biopsy demonstrates acute cellular or humoral rejection of Banff\[2\] Grade 1B or greater; or presumed rejection in the absence of biopsy-proven rejection, the participant is treated for an unexplained 20% increase in serum creatinine. \[2\] Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999 |
| Time From Transplantation to Acute Rejection in Participants for Whom Acute Rejection Occurred During the 1 Year Post-transplant Period | Transplantation to acute rejection (up to one year post-transplant) | Time (days) to acute rejection\[1\] for participants occurring during the year following transplantation 1\] Acute rejection is defined as a biopsy-proven rejection: a renal biopsy demonstrates acute cellular or humoral rejection of Banff\[2\] Grade 1B or greater; or presumed rejection in the absence of biopsy-proven rejection, the participant is treated for an unexplained 20% increase in serum creatinine. \[2\] Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999 |
| Number of Deaths Stratified by Sirolimus Withdrawal Status | Transplantation to Death (up to four years post-transplant) | Participants who died during the study, all cause(s) |
| Number of Participants Who Experienced Graft Loss Stratified by Sirolimus Withdrawal Status | Transplantation to Graft Loss (up to four years post-transplantation) | Participants who experienced graft loss\[1\] during study \[1\]Graft loss is defined as the institution of chronic dialysis (at least 6 consecutive weeks, excluding participants with delayed graft function), transplant nephrectomy, or retransplantation |
| Number of Severe Acute Rejections Stratified by Sirolimus Withdrawal Status | Transplantation to severe acute rejection (up to four years post-transplantation) | Participants who experienced severe acute rejections\[1\] during study 1. Severe acute rejection is defined as that which requires treatment with anti-lymphocyte antibody or is histologically evaluated as Type IIA or greater using the Banff 1997 criteria\[2\] 2. Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999 |
| Number of Acute Rejections in All Enrolled Participants Following Sirolimus Withdrawal | Transplantation to end of study (up to four years post-transplant) | Following sirolimus withdrawal, the number of acute rejections\[1\] in all enrolled participants 1\] Acute rejection is defined as a biopsy-proven rejection: a renal biopsy demonstrates acute cellular or humoral rejection of Banff\[2\] Grade 1B or greater; or presumed rejection in the absence of biopsy-proven rejection, the participant is treated for an unexplained 20% increase in serum creatinine. \[2\] Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999 |
| Number of Alemtuzumab Associated Adverse Events, Stratified by Sirolimus Withdrawal Status | Transplantation to end of study (up to four years post-transplant) | — |
| Number of Tacrolimus Associated Adverse Events, Stratified by Sirolimus Withdrawal Status | Transplantation to end of study (up to four years post-transplant) | — |
| Number of Sirolimus Associated Adverse Events, Stratified by Sirolimus Withdrawal Status | Transplantation to end of study (up to four years post-transplant) | — |
| Number of Side Effects of Conventional Immunosuppression, Stratified by Withdrawal Status | Transplantation to end of study (up to four years post-transplant) | Side effects of conventional immunosuppression include increased body weight and hypertension |
| Change in Renal Function as Measured by Serum Creatinine, Stratified by Withdrawal Status | Transplantation to end of study (up to four years post-transplant) | Mean change from transplantation to Month 48 in serum creatinine. Normal serum creatinine range is from 0.7 - 1.4 mg/dL. In a transplant population, starting serum creatinine is higher than normal range. A negative change indicates better renal function |
| Number of Participants Requiring Anti-lymphocyte Therapy for an Acute Rejection, Stratified by Sirolimus Withdrawal Status | Transplantation to acute rejection (up to four years post-transplantation) | Participants who experienced acute rejection\[1\] during study which required anti-lymphocyte (OKT3, ATG) therapy 1\] Acute rejection is defined as a biopsy-prove rejection: a renal biopsy demonstrates acute cellular or humoral rejection of Banff\[2\] Grade 1B or greater; or presumed rejection in the absence of biopsy-proven rejection, the participant is treated for an unexplained 20% increase in serum creatinine. \[2\] Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999 |
Countries
United States
Participant flow
Recruitment details
For this trial, one center in the United States enrolled ten eligible adult recipients of first kidney transplants (0-3 human leukocyte antigen (HLA)-antigen mismatch) from February 2005 to February 2006
Pre-assignment details
At a screening visit, participants underwent procedures to establish inclusion/exclusion criteria and then sign the informed consent form. Refer to inclusion and exclusion criteria section for more details
Participants by arm
| Arm | Count |
|---|---|
| Alemtuzumab Recipients of first kidney transplants (0-3 HLA antigen mismatch) received induction therapy with alemtuzumab (1 dose \[30 mg\]each day, Days 0 \[transplant day\], 1 and 2, administered intravenously) , tacrolimus (the dose was initially 2 mg twice daily by mouth, and adjusted to maintain target blood levels of 4 to 8 ng/mL from Day 1 to Day 60) and sirolimus (the initial dose was 2 mg/day by mouth started \<= 48 hours post-transplant, subsequently adjusted to achieve trough levels of 8 to 12 ng/mL through Month 12), followed by sirolimus withdrawal as tolerated | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Alemtuzumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 45.3 years STANDARD_DEVIATION 10.5 |
| Pre-Transplant Dialysis Dialysis - Unknown Type | 0 Participants |
| Pre-Transplant Dialysis Hemodialysis | 5 Participants |
| Pre-Transplant Dialysis Hemodialysis and Peritoneal Dialysis | 0 Participants |
| Pre-Transplant Dialysis Participants without pre-transplant dialysis | 5 Participants |
| Pre-Transplant Dialysis Peritoneal Dialysis | 0 Participants |
| Primary Cause of Renal Failure Cystic/Polycystic Kidney Disease | 4 Participants |
| Primary Cause of Renal Failure Diabetes Mellitus | 1 Participants |
| Primary Cause of Renal Failure Etiology Uncertain | 2 Participants |
| Primary Cause of Renal Failure Glomerulonephritis | 0 Participants |
| Primary Cause of Renal Failure Hypertension | 0 Participants |
| Primary Cause of Renal Failure IgA Nephropathy | 2 Participants |
| Primary Cause of Renal Failure Obstructive/Reflux Nephropathy | 1 Participants |
| Primary Cause of Renal Failure Other | 0 Participants |
| Primary Cause of Renal Failure Post-streptococcal Glomerular Nephritis | 0 Participants |
| Primary Cause of Renal Failure Pyelonephritis/Interstitial Nephritis | 0 Participants |
| Primary Cause of Renal Failure Systemic Lupus Erythematosus | 0 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 5 / 10 |
Outcome results
Primary
Number of Acute Rejections in All Enrolled Participants
Number of acute rejections\[1\] in all enrolled subjects from the time of transplantation to the end of the trial (four years post-transplant) 1. Acute rejection is defined as a biopsy-proven rejection: a renal biopsy demonstrates acute cellular or humoral rejection of Banff\[2\] Grade 1B or greater; or presumed rejection in the absence of biopsy-proven rejection, the participant is treated for an unexplained 20% increase in serum creatinine. 2. Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999
Time frame: Four years post-transplant
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alemtuzumab | Number of Acute Rejections in All Enrolled Participants | 1 Rejection Events |
95% CI: [0.01, 0.34]95% Confidence Interval
Secondary
Change in Renal Function as Measured by Serum Creatinine, Stratified by Withdrawal Status
Mean change from transplantation to Month 48 in serum creatinine. Normal serum creatinine range is from 0.7 - 1.4 mg/dL. In a transplant population, starting serum creatinine is higher than normal range. A negative change indicates better renal function
Time frame: Transplantation to end of study (up to four years post-transplant)
Population: Intent-to-treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alemtuzumab | Change in Renal Function as Measured by Serum Creatinine, Stratified by Withdrawal Status | -4.2 mg/dL | Standard Deviation 2.3 |
| Alemtuzumab (Not Withdrawn From Sirolimus) | Change in Renal Function as Measured by Serum Creatinine, Stratified by Withdrawal Status | -5.4 mg/dL | Standard Deviation 2.7 |
Secondary
Number of Acute Rejections Between Initiation of Sirolimus Withdrawal and End of Study
Acute rejections\[1\] between initiation of sirolimus withdrawal and end of study 1\] Acute rejection is defined as a biopsy-proven rejection: a renal biopsy demonstrates acute cellular or humoral rejection of Banff\[2\] Grade 1B or greater; or presumed rejection in the absence of biopsy-proven rejection, the participant is treated for an unexplained 20% increase in serum creatinine. \[2\] Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999
Time frame: Initiation of sirolimus to end of study (up to four years post-transplant)
Population: Sirolimus withdrawal initiation participant sample
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alemtuzumab | Number of Acute Rejections Between Initiation of Sirolimus Withdrawal and End of Study | 0 Rejection Events |
95% CI: [0, 0.7]95% Confidence Interval
Secondary
Number of Acute Rejections in All Enrolled Participants Following Sirolimus Withdrawal
Following sirolimus withdrawal, the number of acute rejections\[1\] in all enrolled participants 1\] Acute rejection is defined as a biopsy-proven rejection: a renal biopsy demonstrates acute cellular or humoral rejection of Banff\[2\] Grade 1B or greater; or presumed rejection in the absence of biopsy-proven rejection, the participant is treated for an unexplained 20% increase in serum creatinine. \[2\] Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999
Time frame: Transplantation to end of study (up to four years post-transplant)
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alemtuzumab | Number of Acute Rejections in All Enrolled Participants Following Sirolimus Withdrawal | 0 Rejection Events |
95% CI: [0, 0.3]95% Confidence Interval
Secondary
Number of Alemtuzumab Associated Adverse Events, Stratified by Sirolimus Withdrawal Status
Time frame: Transplantation to end of study (up to four years post-transplant)
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alemtuzumab | Number of Alemtuzumab Associated Adverse Events, Stratified by Sirolimus Withdrawal Status | 2 adverse events |
| Alemtuzumab (Not Withdrawn From Sirolimus) | Number of Alemtuzumab Associated Adverse Events, Stratified by Sirolimus Withdrawal Status | 8 adverse events |
Secondary
Number of Deaths Stratified by Sirolimus Withdrawal Status
Participants who died during the study, all cause(s)
Time frame: Transplantation to Death (up to four years post-transplant)
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alemtuzumab | Number of Deaths Stratified by Sirolimus Withdrawal Status | 0 deaths |
| Alemtuzumab (Not Withdrawn From Sirolimus) | Number of Deaths Stratified by Sirolimus Withdrawal Status | 0 deaths |
95% CI: [0, 0.3]95% Confidence Interval
Secondary
Number of Participants Requiring Anti-lymphocyte Therapy for an Acute Rejection, Stratified by Sirolimus Withdrawal Status
Participants who experienced acute rejection\[1\] during study which required anti-lymphocyte (OKT3, ATG) therapy 1\] Acute rejection is defined as a biopsy-prove rejection: a renal biopsy demonstrates acute cellular or humoral rejection of Banff\[2\] Grade 1B or greater; or presumed rejection in the absence of biopsy-proven rejection, the participant is treated for an unexplained 20% increase in serum creatinine. \[2\] Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999
Time frame: Transplantation to acute rejection (up to four years post-transplantation)
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alemtuzumab | Number of Participants Requiring Anti-lymphocyte Therapy for an Acute Rejection, Stratified by Sirolimus Withdrawal Status | 0 participants |
| Alemtuzumab (Not Withdrawn From Sirolimus) | Number of Participants Requiring Anti-lymphocyte Therapy for an Acute Rejection, Stratified by Sirolimus Withdrawal Status | 0 participants |
95% CI: [0, 0.4]95% Confidence Interval
95% CI: [0, 0.8]95% Confidence Interval
Secondary
Number of Participants Who Experienced Graft Loss Stratified by Sirolimus Withdrawal Status
Participants who experienced graft loss\[1\] during study \[1\]Graft loss is defined as the institution of chronic dialysis (at least 6 consecutive weeks, excluding participants with delayed graft function), transplant nephrectomy, or retransplantation
Time frame: Transplantation to Graft Loss (up to four years post-transplantation)
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alemtuzumab | Number of Participants Who Experienced Graft Loss Stratified by Sirolimus Withdrawal Status | 0 participants |
| Alemtuzumab (Not Withdrawn From Sirolimus) | Number of Participants Who Experienced Graft Loss Stratified by Sirolimus Withdrawal Status | 0 participants |
95% CI: [0, 0.3]95% Confidence Interval
Secondary
Number of Severe Acute Rejections Stratified by Sirolimus Withdrawal Status
Participants who experienced severe acute rejections\[1\] during study 1. Severe acute rejection is defined as that which requires treatment with anti-lymphocyte antibody or is histologically evaluated as Type IIA or greater using the Banff 1997 criteria\[2\] 2. Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999
Time frame: Transplantation to severe acute rejection (up to four years post-transplantation)
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alemtuzumab | Number of Severe Acute Rejections Stratified by Sirolimus Withdrawal Status | 0 Rejection Events |
| Alemtuzumab (Not Withdrawn From Sirolimus) | Number of Severe Acute Rejections Stratified by Sirolimus Withdrawal Status | 0 Rejection Events |
95% CI: [0, 0.4]95% Confidence Interval
95% CI: [0, 0.8]95% Confidence Interval
Secondary
Number of Side Effects of Conventional Immunosuppression, Stratified by Withdrawal Status
Side effects of conventional immunosuppression include increased body weight and hypertension
Time frame: Transplantation to end of study (up to four years post-transplant)
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alemtuzumab | Number of Side Effects of Conventional Immunosuppression, Stratified by Withdrawal Status | 2 side effects |
| Alemtuzumab (Not Withdrawn From Sirolimus) | Number of Side Effects of Conventional Immunosuppression, Stratified by Withdrawal Status | 6 side effects |
Secondary
Number of Sirolimus Associated Adverse Events, Stratified by Sirolimus Withdrawal Status
Time frame: Transplantation to end of study (up to four years post-transplant)
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alemtuzumab | Number of Sirolimus Associated Adverse Events, Stratified by Sirolimus Withdrawal Status | 2 adverse events |
| Alemtuzumab (Not Withdrawn From Sirolimus) | Number of Sirolimus Associated Adverse Events, Stratified by Sirolimus Withdrawal Status | 7 adverse events |
Secondary
Number of Tacrolimus Associated Adverse Events, Stratified by Sirolimus Withdrawal Status
Time frame: Transplantation to end of study (up to four years post-transplant)
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alemtuzumab | Number of Tacrolimus Associated Adverse Events, Stratified by Sirolimus Withdrawal Status | 0 adverse events |
| Alemtuzumab (Not Withdrawn From Sirolimus) | Number of Tacrolimus Associated Adverse Events, Stratified by Sirolimus Withdrawal Status | 2 adverse events |
Secondary
Time From Transplantation to Acute Rejection in Participants for Whom Acute Rejection Occurred During the 1 Year Post-transplant Period
Time (days) to acute rejection\[1\] for participants occurring during the year following transplantation 1\] Acute rejection is defined as a biopsy-proven rejection: a renal biopsy demonstrates acute cellular or humoral rejection of Banff\[2\] Grade 1B or greater; or presumed rejection in the absence of biopsy-proven rejection, the participant is treated for an unexplained 20% increase in serum creatinine. \[2\] Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999
Time frame: Transplantation to acute rejection (up to one year post-transplant)
Population: Participants with acute rejections for whom sirolimus withdrawal was not initiated
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alemtuzumab | Time From Transplantation to Acute Rejection in Participants for Whom Acute Rejection Occurred During the 1 Year Post-transplant Period | 274 Days |
Secondary
Time From Transplantation to Acute Rejection in Participants for Whom Sirolimus Withdrawal Was Not Initiated
Time (days) to acute rejection\[1\] for participants where sirolimus was not initiated 1\] Acute rejection is defined as a biopsy-proven rejection: a renal biopsy demonstrates acute cellular or humoral rejection of Banff\[2\] Grade 1B or greater; or presumed rejection in the absence of biopsy-proven rejection, the participant is treated for an unexplained 20% increase in serum creatinine. \[2\] Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999
Time frame: Transplantation to acute rejection (up to four years post-transplantation)
Population: Participants for whom sirolimus withdrawal was not initiated
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alemtuzumab | Time From Transplantation to Acute Rejection in Participants for Whom Sirolimus Withdrawal Was Not Initiated | 274 Days |