Randomized Conversion of Calcineurin-Inhibitors in Renal Allograft Recipients

• Sponsor: Northwestern University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00866879
• Collaborator: Wyeth is now a wholly owned subsidiary of Pfizer (Industry)
• Enrollment: 275
• Location: 1
• Arms: 3
• Actual Duration (Months): 141
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

This study is being done to investigate the impact of changing immunosuppressive medications from tacrolimus (Prograf®) to sirolimus (Rapamune®) between 6 and 24 months post transplant. The primary purpose of this research study is to evaluate whether the use of mycophenolate mofetil(MMF)/Cellcept® and tacrolimus(TAC)/Prograf® (Group 1) or mycophenolate mofetil(MMF)/Cellcept® and sirolimus/Rapamune® (Group 2) impacts the incidence of acute cellular rejection in post kidney transplant patients. This study will examine whether switching from tacrolimus to sirolimus will better preserve long-term kidney function.

Condition or Disease	Intervention/Treatment	Phase
Renal Transplant Rejection	Drug: Sirolimus; Other: Demographic Data, Medical History, and Donor Data; Procedure: Blood Draws for Control Group; Procedure: Blood Draws for Experimental Group; Procedure: Donor Blood Draws; Other: Donor Information; Procedure: Kidney Biopsy	Phase 4

Detailed Description

For this research study, between 6 and 24 Months post-transplant, we plan to prospectively randomize 2:1 renal transplant patients to either:

• Substitute tacrolimus (TAC) with sirolimus and continue mycophenolate mofetil (MMF) or

• Continue with tacrolimus (TAC) and mycophenolate mofetil (MMF)

A total of 400 patients are expected to be screened for the randomization. We expect to randomize 275 renal transplant patients into this protocol (275 donors to be recruited).

The following data will be collected at the time of randomization:

Recipient demographics: (i) age at transplantation, (ii) sex, and (iii) race.

Clinical history: (i) causes of end-stage renal disease, and (ii) past medical history.

Transplant related information: (i) donor age, (ii) cadaveric versus living kidney transplant, (iii) histocompatibility and cross match data, (iv) viral serology, (v) history of acute rejection and delayed graft function, (vi) use of induction therapy and immunosuppressants, (vii) use of ACEI and/or ARB, and (viii) level of renal allograft function-estimated GFR (e-GFR(12) using MDRD formula, proteinuria.

Peripheral blood leukocytes will be obtained from renal transplant recipients for baseline (prior to randomization) lymphocytes functional activity and characterization of lymphocytes subpopulations by flow cytometry analysis.

Peripheral donor leukocytes (from living donor patients) will also be obtained at the time of randomization. These donor leukocytes will be used as stimulator cells to study the functional activity of the recipient's lymphocytes function.

The recipients assigned to continue with tacrolimus and MMF will be routinely followed at the outpatient Comprehensive Transplant Center (CTC) with monthly labs. In addition to labs at baseline pre-randomization, 6, 12 and 24 Months post-randomization, peripheral blood leukocytes will be obtained to study lymphocytes functional activity and to characterize lymphocytes subpopulations by flow cytometry analysis.

Post randomization: The recipients assigned to switch from tacrolimus to sirolimus and continue with MMF will be routinely followed at the CTC with monthly labs. During the period of conversion from tacrolimus to sirolimus, weekly labs will be obtained to monitor renal function and bone marrow function. In addition to labs at baseline pre-randomization, 6, 12 and 24 Months post-randomization, peripheral blood leukocytes will be obtained to study lymphocytes functional activity to characterize lymphocytes subpopulations by flow cytometry analysis. Urine will be collected to assess tubular toxicity by evaluating urinary biomarkers.

Both groups of patients will be followed for 2 years post-randomization. In addition to monitoring renal allograft function, we will evaluate the incidence of acute rejection, patient and graft survival, impact of CI conversion on the lipid profile, incidence of hypertension, malignancies, opportunistic infections, and post-transplant diabetes mellitus (DM). For those willing to undergo an optional kidney biopsy, one will be performed at the end of the second year in order to evaluate renal allograft pathology and renal allograft tissue gene expression profiles of the two groups.

With the peripheral leukocytes obtained at baseline prior to randomization and at 6, 12 and 24 Months post-randomization, we will investigate possible modifications of lymphocytes function and the lymphocytes subpopulations that might have occurred as a consequence of the switch from tacrolimus to sirolimus.

Obtaining renal allograft tissue samples at 24 months post randomization can have potential important ramifications to help explain the mechanisms of fibrosis and tubular atrophy typically associated with CI and the role of CI elimination with the substitution of sirolimus (SRL). All data will then be analyzed comparing gene expression profiles of peripheral blood (Pax gene tubes are routinely collected at the different time points as part of the original study). Based on power analysis, we will perform 24 months post randomization biopsies in 70% of the total subjects enrolled in the study (approximately 46 subjects from the tacrolimus/MMF group and approximately 93 subjects from the sirolimus/MMF group).

We plan to obtain renal allograft biopsies at 24 Months for those that consent for this additional biopsy. This will be compared to the standard of care 12 months post-transplant biopsy to allow us to address the effect of immunosuppressive modifications on renal allograft pathology at 24 months post randomization. Renal allograft biopsies will also be stored in RNA later to further extend our knowledge on the effect of CI free immunosuppression on gene expression profiles.

Study Design

• Study Type: Interventional
• Actual Enrollment: 275 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Randomized Conversion of Calcineurin-Inhibitors(Tacrolimus to Sirolimus),6-24 Months Post Transplant Prednisone-Free Immunosuppression Regimen: Impact of Incidence of Acute Cellular Rejection,Renal Allograft Function & Lymphocytes Function
• Actual Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Dec 1, 2017
• Actual Study Completion Date: Mar 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Control Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.	Other: Demographic Data, Medical History, and Donor Data; Age at transplant, sex, race, cause of end-stage renal disease, medical history, donor age, cadaveric vs. living kidney transplant, histocompatibility/cross match data, viral serology, history of acute rejection and delayed graft function, use of induction therapy and immunosuppressants, use of Angiotensin Converting Enzyme Inhibitor (ACEI) and/or Angiotensin Receptor Blockers (ARB) level of renal allograft function-estimated GFR (e-GFR(12) using Modification of Diet in Renal Disease (MDRD) formula, proteinuria.; Procedure: Blood Draws for Control Group; Subjects maintaining standard of care drug treatment of TAC and MMF will have monthly labs in addition to the baseline pre-randomization labs, at 6, 12, and 24 Months post-randomization. Peripheral blood leukocytes will be obtained.; Procedure: Kidney Biopsy; Kidney biopsy at 24 Months to compare to the standard of care biopsy taken at 12 Months. This information will help evaluate renal allograft pathology and renal allograft tissue gene expression profiles of the two groups. Renal allograft biopsies will be stored in RNA later (preservative) to further extend knowledge on the effect of calcineurin-inhibitors (CI) free immunosuppression on gene expression profiles.
Experimental: Transition to Sirolimus Group Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus	Drug: Sirolimus; Sirolimus will initially be given at a dose of 2-4 mg orally (PO) daily. The dose will be modified to achieve 24 hours trough concentrations of 6-10 ng/ml by high-performance liquid chromatography (HPLC) assay. This medication will be given in an open label fashion. The first dose of sirolimus will be given at the time of randomization to those patients assigned to have tacrolimus switched to sirolimus.; Other Names: Rapamune ; Other: Demographic Data, Medical History, and Donor Data; Age at transplant, sex, race, cause of end-stage renal disease, medical history, donor age, cadaveric vs. living kidney transplant, histocompatibility/cross match data, viral serology, history of acute rejection and delayed graft function, use of induction therapy and immunosuppressants, use of Angiotensin Converting Enzyme Inhibitor (ACEI) and/or Angiotensin Receptor Blockers (ARB) level of renal allograft function-estimated GFR (e-GFR(12) using Modification of Diet in Renal Disease (MDRD) formula, proteinuria.; Procedure: Blood Draws for Experimental Group; This group will have monthly labs taken but will also have weekly labs during the period of conversion to monitor renal function and bone marrow function. In addition to the baseline pre-randomization labs, and labs collected at 6, 12, and 24 Months post-randomization, peripheral blood leukocytes will be obtained.; Procedure: Kidney Biopsy; Kidney biopsy at 24 Months to compare to the standard of care biopsy taken at 12 Months. This information will help evaluate renal allograft pathology and renal allograft tissue gene expression profiles of the two groups. Renal allograft biopsies will be stored in RNA later (preservative) to further extend knowledge on the effect of calcineurin-inhibitors (CI) free immunosuppression on gene expression profiles.
Other: Donors Data and blood samples from the donors are collected in this study to contribute to the general knowledge to be used in assessing the two donor recipient groups, which are the target of this study.	Procedure: Donor Blood Draws; Peripheral blood leukocytes from living donors obtained at the time of randomization. These donor leukocytes will be used as stimulator cells to study the functional activity of the recipient's lymphocytes function.; Other: Donor Information; Donor age, cadaveric vs. living donor, and histocompatibility and cross match to recipient

Outcome Measures

Primary Outcome Measures

1. Incidence of Acute Cellular Rejection [Assessed at 6 Months, 12 Months, 24 Months, months 24 reported]

   The primary purpose of this research study is to evaluate whether the use of mycophenolate mofetil/Cellcept ® and either tacrolimus/Prograf ® (Group #1) or mycophenolate mofetil/Cellcept ® and sirolimus/Rapamune® (Group #2) impacts the incidence of acute cellular rejection in post-kidney transplant patients. This study will examine whether switching from tacrolimus to sirolimus will better preserve long-term kidney function.

Secondary Outcome Measures

1. Renal Allograft Function Calculated With e-GFR and Proteinuria [Assessed at 6 Months, 12 Months, 24 Months, months 24 reported]

   Evaluate whether CI conversion (tacrolimus→sirolimus) contributes positively or negatively on the renal allograft function calculated with e-GFR and proteinuria

2. Evaluate if CI Conversion Impacts on Lipid Profile, Incidence of Hypertension, Malignancies, and Opportunistic Infections and Post-transplant DM [Assessed at 6 Months, 12 Months, 24 Months, months 24 reported]

   In addition to monitoring renal allograft function, evaluation will be conducted on the incidence of acute rejection, patient and graft survival, the impact of CI conversion on the lipid profile, the incidence of hypertension, malignancies, opportunistic infections and post-transplant DM (de novo diabetes mellitus).

3. Patient and Graft Survival [Assessed at 6 Months, 12 Months, 24 Months, months 24 reported]

   This study also reviews the impact of the immunosuppressive medications on patient and graft survival.

4. Percentage of Regulatory T Cells [Assessed at 6 Months, 12 Months, 24 Months, months 24 reported]

   Specifically we reported here the percentage of regulatory T cells that were present in the two groups at 24 months post randomization. With peripheral leukocytes taken at baseline (first visit) prior to randomization and at 6, 12 and 24 Months post-randomization, researchers will also review possible modifications of lymphocytes function and of the lymphocytes subpopulations that might have occurred as a consequence of the switch from tacrolimus to sirolimus (randomization).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subjects should be adults ≥ 18- ≤ 70 years of age

2. Subjects can be either gender or of any ethnic background

3. Subjects should be single organ recipients (kidney only)

4. Subjects must be able to understand the protocol and provide informed consent.

Exclusion Criteria:

1. Subjects with end-stage renal disease (ESRD) secondary to primary focal segmental glomerulonephritis (FSGS).

2. Inability to comply with study procedures

3. Inability to sign the informed consent

4. Subjects with a significant or active infection

5. Subjects who are pregnant or nursing females

6. Subjects with a history of severe hyperlipidemia not controlled with statins, patients with at total cholesterol of > 400 mg/dl

7. Subjects with a platelet count <100,000mm3 white blood cell (WBC)< 2,000mm3

8. Subjects with severe proteinuria at the time of randomization (>2gm/day)

9. Subjects with more then 2 episodes of acute cellular rejection post transplantation will be excluded from this study

10. An estimated GFR<40 cc/min

11. A history of malignancy during the post-transplant period (other than treated basal cell cancer and/or squamous cell cancer)

12. Subjects, who, due to the existence of a surgical, medical or psychiatric condition, other than the current transplant, which in the opinion of the investigator, precludes enrollment into this trial

13. A history of albumin-creatinine ratio (ACR) during the most recent previous 3 months prior to randomization

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern Memorial Hospital	Chicago	Illinois	United States	60611

Sponsors and Collaborators

• Northwestern University
• Wyeth is now a wholly owned subsidiary of Pfizer

Investigators

• Principal Investigator: Lorenzo Gallon, MD, Northwestern Univesity, Northwestern Memorial Hospital, Northwestern Medical Faculty Foundation

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 1, 2012

More Information

Publications

• Bennett WM, DeMattos A, Meyer MM, Andoh T, Barry JM. Chronic cyclosporine nephropathy: the Achilles' heel of immunosuppressive therapy. Kidney Int. 1996 Oct;50(4):1089-100. Review.
• Bennett WM. Insights into chronic cyclosporine nephrotoxicity. Int J Clin Pharmacol Ther. 1996 Nov;34(11):515-9. Review.
• Fisher NC, Nightingale PG, Gunson BK, Lipkin GW, Neuberger JM. Chronic renal failure following liver transplantation: a retrospective analysis. Transplantation. 1998 Jul 15;66(1):59-66.
• Goldstein DJ, Zuech N, Sehgal V, Weinberg AD, Drusin R, Cohen D. Cyclosporine-associated end-stage nephropathy after cardiac transplantation: incidence and progression. Transplantation. 1997 Mar 15;63(5):664-8.
• Gonwa TA, Mai ML, Melton LB, Hays SR, Goldstein RM, Levy MF, Klintmalm GB. End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: risk of development and treatment. Transplantation. 2001 Dec 27;72(12):1934-9.
• Hornberger J, Best J, Geppert J, McClellan M. Risks and costs of end-stage renal disease after heart transplantation. Transplantation. 1998 Dec 27;66(12):1763-70.
• Myers BD, Ross J, Newton L, Luetscher J, Perlroth M. Cyclosporine-associated chronic nephropathy. N Engl J Med. 1984 Sep 13;311(11):699-705.
• Myers BD. Cyclosporine nephrotoxicity. Kidney Int. 1986 Dec;30(6):964-74. Review.
• Ojo AO, Held PJ, Port FK, Wolfe RA, Leichtman AB, Young EW, Arndorfer J, Christensen L, Merion RM. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med. 2003 Sep 4;349(10):931-40.
• Puschett JB, Greenberg A, Holley J, McCauley J. The spectrum of ciclosporin nephrotoxicity. Am J Nephrol. 1990;10(4):296-309. Review.
• Stoves J, Lindley EJ, Barnfield MC, Burniston MT, Newstead CG. MDRD equation estimates of glomerular filtration rate in potential living kidney donors and renal transplant recipients with impaired graft function. Nephrol Dial Transplant. 2002 Nov;17(11):2036-7.
• Young EW, Ellis CN, Messana JM, Johnson KJ, Leichtman AB, Mihatsch MJ, Hamilton TA, Groisser DS, Fradin MS, Voorhees JJ. A prospective study of renal structure and function in psoriasis patients treated with cyclosporin. Kidney Int. 1994 Oct;46(4):1216-22.

• Responsible Party: Lorenzo Gallon, Associate Professor, Northwestern University
• ClinicalTrials.gov Identifier: NCT00866879
• Other Study ID Numbers: STU8308 0773-017; 0468H1-4472
• First Posted: Mar 23, 2009
• Last Update Posted: Jun 28, 2019
• Last Verified: Jun 1, 2019

• Keywords provided by Lorenzo Gallon, Associate Professor, Northwestern University: Sirolimus; Rapamune; Immunosuppression; Renal allograft function; Lymphocytes function
• Additional relevant MeSH terms: Sirolimus

Study Results

Participant Flow

Pre-assignment Detail	Donor participants were no part of our outcome analysis because their participation was only on the basis of providing blood for testing the immune system of the recipients. The analysis of the recipients was intention to treat therefore all recipient participants completed the study period

Arm/Group Title	Control	Transition to Sirolimus Group
Arm/Group Description	Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.	Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus
Period Title: Overall Study
STARTED	90	185
COMPLETED	90	185
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Control	Transition to Sirolimus Group	Total
Arm/Group Description	Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.	Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus	Total of all reporting groups
Overall Participants	90	185	275
Age, Customized (years) [Mean (Standard Deviation) ]
Age in years	39.2 (12.6)	38.8 (12.5)	38.9 (12.6)
Sex/Gender, Customized (Count of Participants)
Sex male	55 61.1%	106 57.3%	161 58.5%
Sex female	35 38.9%	79 42.7%	114 41.5%
Race/Ethnicity, Customized (Count of Participants)
white	44 48.9%	83 44.9%	127 46.2%
AA	24 26.7%	37 20%	61 22.2%
Hispanic	17 18.9%	45 24.3%	62 22.5%
other	5 5.6%	20 10.8%	25 9.1%
Region of Enrollment (participants) [Number]
United States	90 100%	185 100%	275 100%
HLA mismatch (HLA antigens) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [HLA antigens]	3.9 (1.7)	3.61 (1.82)	3.8 (1.8)
Donor type (Count of Participants)
Living donors	63 70%	130 70.3%	193 70.2%
Cadaveric kidneys	27 30%	55 29.7%	82 29.8%
PRA >20% (Count of Participants)
Count of Participants [Participants]	14 15.6%	24 13%	38 13.8%
Diabetis mellitus (Count of Participants)
Count of Participants [Participants]	26 28.9%	69 37.3%	95 34.5%
Elevated blood pressure (Count of Participants)
Count of Participants [Participants]	76 84.4%	158 85.4%	234 85.1%
Coronary artery disease (CAD) (Count of Participants)
Count of Participants [Participants]	10 11.1%	31 16.8%	41 14.9%
Smoking (Count of Participants)
Count of Participants [Participants]	9 10%	29 15.7%	38 13.8%

Outcome Measures

1. Primary Outcome

Title	Incidence of Acute Cellular Rejection
Description	The primary purpose of this research study is to evaluate whether the use of mycophenolate mofetil/Cellcept ® and either tacrolimus/Prograf ® (Group #1) or mycophenolate mofetil/Cellcept ® and sirolimus/Rapamune® (Group #2) impacts the incidence of acute cellular rejection in post-kidney transplant patients. This study will examine whether switching from tacrolimus to sirolimus will better preserve long-term kidney function.
Time Frame	Assessed at 6 Months, 12 Months, 24 Months, months 24 reported

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Transition to Sirolimus Group
Arm/Group Description	Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.	Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus
Measure Participants	90	185
Count of Participants [Participants]	7 7.8%	31 16.8%

2. Secondary Outcome

Title	Renal Allograft Function Calculated With e-GFR and Proteinuria
Description	Evaluate whether CI conversion (tacrolimus→sirolimus) contributes positively or negatively on the renal allograft function calculated with e-GFR and proteinuria
Time Frame	Assessed at 6 Months, 12 Months, 24 Months, months 24 reported

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Transition to Sirolimus Group
Arm/Group Description	Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.	Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus
Measure Participants	90	185
Mean (Standard Deviation) [mL/min]	57.6 (20.4)	58.4 (25.2)

3. Secondary Outcome

Title	Evaluate if CI Conversion Impacts on Lipid Profile, Incidence of Hypertension, Malignancies, and Opportunistic Infections and Post-transplant DM
Description	In addition to monitoring renal allograft function, evaluation will be conducted on the incidence of acute rejection, patient and graft survival, the impact of CI conversion on the lipid profile, the incidence of hypertension, malignancies, opportunistic infections and post-transplant DM (de novo diabetes mellitus).
Time Frame	Assessed at 6 Months, 12 Months, 24 Months, months 24 reported

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Transition to Sirolimus Group
Arm/Group Description	Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.	Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus
Measure Participants	90	185
Infections	33	83
Malignancies	4	9
Proteinura	12	61
Hyperlipidemia	9	19
NODAT	3	2
BK viremia	15	28
BK nephropathy	1	5
Neutropenia	22	35

4. Secondary Outcome

Title	Patient and Graft Survival
Description	This study also reviews the impact of the immunosuppressive medications on patient and graft survival.
Time Frame	Assessed at 6 Months, 12 Months, 24 Months, months 24 reported

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Transition to Sirolimus Group
Arm/Group Description	Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.	Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus
Measure Participants	90	185
Kidney transplant loss	4	12
Patient death	3	10

5. Secondary Outcome

Title	Percentage of Regulatory T Cells
Description	Specifically we reported here the percentage of regulatory T cells that were present in the two groups at 24 months post randomization. With peripheral leukocytes taken at baseline (first visit) prior to randomization and at 6, 12 and 24 Months post-randomization, researchers will also review possible modifications of lymphocytes function and of the lymphocytes subpopulations that might have occurred as a consequence of the switch from tacrolimus to sirolimus (randomization).
Time Frame	Assessed at 6 Months, 12 Months, 24 Months, months 24 reported

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Transition to Sirolimus Group
Arm/Group Description	Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.	Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus
Measure Participants	90	185
Mean (Standard Deviation) [% of Treg Cells]	75 (7.1)	98 (10.8)

Adverse Events

Time Frame	24 months
Adverse Event Reporting Description	Donor participants were no part of our outcome analysis because their participation was only on the basis of providing blood for testing the immune system of the recipients. The analysis of the recipients was intention to treat therefore all recipient participants completed the study period
Arm/Group Title	Control		Transition to Sirolimus
Arm/Group Description	Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus. Patients were followed for 24 months post randomization		Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus. Patients were followed for 24 months post randomization
All Cause Mortality
	Control		Transition to Sirolimus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/90 (3.3%)		10/185 (5.4%)
Serious Adverse Events
	Control		Transition to Sirolimus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/90 (46.7%)		117/185 (63.2%)
Blood and lymphatic system disorders
Neutropenia	22/90 (24.4%)	22	35/185 (18.9%)	35
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignancies	4/90 (4.4%)	4	9/185 (4.9%)	9
Renal and urinary disorders
Renal allograft loss	4/90 (4.4%)	4	12/185 (6.5%)	12
Proteinuria	12/90 (13.3%)	12	61/185 (33%)	61
Other (Not Including Serious) Adverse Events
	Control		Transition to Sirolimus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	58/90 (64.4%)		135/185 (73%)
Cardiac disorders
Hyperlipidemia	9/90 (10%)	9	19/185 (10.3%)	19
Endocrine disorders
Diabetes	3/90 (3.3%)	3	2/185 (1.1%)	3
Infections and infestations
Infections	33/90 (36.7%)	33	83/185 (44.9%)	83
Renal and urinary disorders
BK viremia	15/90 (16.7%)	15	28/185 (15.1%)	28
BK nephropathy	1/90 (1.1%)	1	5/185 (2.7%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.