## Protocol Section
### Identification Module
**NCT ID:** NCT00866879

**Brief Title:** Randomized Conversion of Calcineurin-Inhibitors in Renal Allograft Recipients

**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

#### Organization Study ID Info
**ID:** STU8308 0773-017
#### Organization
**Class:** OTHER
**Full Name:** Northwestern University
#### Secondary ID Infos
**Domain:** Pfizer (Wyeth)
**ID:** 0468H1-4472
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2019-03

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2019-06-28

**Type:** ACTUAL

**Last Update Submit Date:** 2019-06-18

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2017-12

**Type:** ACTUAL

#### Results First Post Date
**Date:** 2019-05-31

**Type:** ACTUAL

**Results First Submit Date:** 2019-04-09

**Results First Submit QC Date:** 2019-05-08

#### Start Date
**Date:** 2007-06

**Type:** ACTUAL

**Status Verified Date:** 2019-06

#### Study First Post Date
**Date:** 2009-03-23
**Type:** ESTIMATED
**Study First Submit Date:** 2009-03-19
**Study First Submit QC Date:** 2009-03-20
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Wyeth is now a wholly owned subsidiary of Pfizer

#### Lead Sponsor

**Class:** OTHER

**Name:** Northwestern University

#### Responsible Party

**Investigator Affiliation:** Northwestern University

**Investigator Full Name:** Lorenzo Gallon

**Investigator Title:** Associate Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Oversight Has DMC:** False

### Description Module

**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.

**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.

### Conditions Module

**Conditions:**

- Renal Transplant Rejection

**Keywords:**

- Sirolimus

- Rapamune

- Immunosuppression

- Renal allograft function

- Lymphocytes function

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** PREVENTION

#### Enrollment Info

**Count:** 275

**Type:** ACTUAL

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.

**Intervention Names:**

- Other: Demographic Data, Medical History, and Donor Data

- Procedure: Blood Draws for Control Group

- Procedure: Kidney Biopsy

**Label:** Control

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Description:** Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus

**Intervention Names:**

- Drug: Sirolimus

- Other: Demographic Data, Medical History, and Donor Data

- Procedure: Blood Draws for Experimental Group

- Procedure: Kidney Biopsy

**Label:** Transition to Sirolimus Group

**Type:** EXPERIMENTAL

#### Arm Group 3

**Description:** 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.

**Intervention Names:**

- Procedure: Donor Blood Draws

- Other: Donor Information

**Label:** Donors

**Type:** OTHER

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Transition to Sirolimus Group

**Description:** 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.

**Name:** Sirolimus

**Other Names:**

- Rapamune

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Control

- Transition to Sirolimus Group

**Description:** 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.

**Name:** Demographic Data, Medical History, and Donor Data

**Type:** OTHER

#### Intervention 3

**Arm Group Labels:**

- Control

**Description:** 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.

**Name:** Blood Draws for Control Group

**Type:** PROCEDURE

#### Intervention 4

**Arm Group Labels:**

- Transition to Sirolimus Group

**Description:** 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.

**Name:** Blood Draws for Experimental Group

**Type:** PROCEDURE

#### Intervention 5

**Arm Group Labels:**

- Donors

**Description:** 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.

**Name:** Donor Blood Draws

**Type:** PROCEDURE

#### Intervention 6

**Arm Group Labels:**

- Donors

**Description:** Donor age, cadaveric vs. living donor, and histocompatibility and cross match to recipient

**Name:** Donor Information

**Type:** OTHER

#### Intervention 7

**Arm Group Labels:**

- Control

- Transition to Sirolimus Group

**Description:** 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.

**Name:** Kidney Biopsy

**Type:** PROCEDURE

### Outcomes Module

#### Primary Outcomes

**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.

**Measure:** Incidence of Acute Cellular Rejection

**Time Frame:** Assessed at 6 Months, 12 Months, 24 Months, months 24 reported

#### Secondary Outcomes

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

**Measure:** Renal Allograft Function Calculated With e-GFR and Proteinuria

**Time Frame:** Assessed at 6 Months, 12 Months, 24 Months, months 24 reported

**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).

**Measure:** Evaluate if CI Conversion Impacts on Lipid Profile, Incidence of Hypertension, Malignancies, and Opportunistic Infections and Post-transplant DM

**Time Frame:** Assessed at 6 Months, 12 Months, 24 Months, months 24 reported

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

**Measure:** Patient and Graft Survival

**Time Frame:** Assessed at 6 Months, 12 Months, 24 Months, months 24 reported

**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).

**Measure:** Percentage of Regulatory T Cells

**Time Frame:** Assessed at 6 Months, 12 Months, 24 Months, months 24 reported

### Eligibility Module

**Eligibility Criteria:** 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

**Maximum Age:** 70 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Chicago

**Country:** United States

**Facility:** Northwestern Memorial Hospital

**State:** Illinois

**Zip:** 60611

#### Overall Officials

**Official 1:**

**Affiliation:** Northwestern Univesity, Northwestern Memorial Hospital, Northwestern Medical Faculty Foundation

**Name:** Lorenzo Gallon, MD

**Role:** PRINCIPAL_INVESTIGATOR

### References Module

#### References

**Citation:** 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. doi: 10.1056/NEJMoa021744.

**PMID:** 12954741

**Citation:** 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. doi: 10.1093/ndt/17.11.2036. No abstract available.

**PMID:** 12401874

**Citation:** 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. doi: 10.1097/00007890-200112270-00012.

**PMID:** 11773892

**Citation:** 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. doi: 10.1097/00007890-199807150-00010.

**PMID:** 9679823

**Citation:** 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. doi: 10.1097/00007890-199812270-00034.

**PMID:** 9884274

**Citation:** 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. doi: 10.1097/00007890-199703150-00009.

**PMID:** 9075835

**Citation:** 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. doi: 10.1056/NEJM198409133111103.

**PMID:** 6382005

**Citation:** 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. doi: 10.1038/ki.1996.415. No abstract available.

**PMID:** 8887265

**Citation:** Bennett WM. Insights into chronic cyclosporine nephrotoxicity. Int J Clin Pharmacol Ther. 1996 Nov;34(11):515-9.

**PMID:** 8937936

**Citation:** Myers BD. Cyclosporine nephrotoxicity. Kidney Int. 1986 Dec;30(6):964-74. doi: 10.1038/ki.1986.280. No abstract available.

**PMID:** 3546916

**Citation:** Puschett JB, Greenberg A, Holley J, McCauley J. The spectrum of ciclosporin nephrotoxicity. Am J Nephrol. 1990;10(4):296-309. doi: 10.1159/000168123. No abstract available.

**PMID:** 2240057

**Citation:** 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. doi: 10.1038/ki.1994.387.

**PMID:** 7861719

## Document Section

### Large Document Module

#### Large Docs

- Date: 2012-11-01

- Filename: Prot_SAP_000.pdf

- Has ICF: False

- Has Protocol: True

- Has SAP: True

- Label: Study Protocol and Statistical Analysis Plan

- Size: 210385

- Type Abbrev: Prot_SAP

- Upload Date: 2019-04-08T16:17

## Derived Section

### Condition Browse Module - Browse Branches

- Abbrev: Rare

- Name: Rare Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: T170

- Name: Acute Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Ancestors

- ID: D000000900

- Term: Anti-Bacterial Agents

- ID: D000000890

- Term: Anti-Infective Agents

- ID: D000000903

- Term: Antibiotics, Antineoplastic

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000000935

- Term: Antifungal Agents

- ID: D000007166

- Term: Immunosuppressive Agents

- ID: D000007155

- Term: Immunologic Factors

- ID: D000045505

- Term: Physiological Effects of Drugs

### Intervention Browse Module - Browse Branches

- Abbrev: Infl

- Name: Anti-Inflammatory Agents

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Infe

- Name: Anti-Infective Agents

### Intervention Browse Module - Browse Leaves

- ID: M14121

- Name: Prednisone

- Relevance: LOW

- As Found: Unknown

- ID: M16975

- Name: Triamcinolone Acetonide

- Relevance: LOW

- As Found: Unknown

- ID: M16974

- Name: Triamcinolone

- Relevance: LOW

- As Found: Unknown

- ID: M237966

- Name: Triamcinolone hexacetonide

- Relevance: LOW

- As Found: Unknown

- ID: M209573

- Name: Triamcinolone diacetate

- Relevance: LOW

- As Found: Unknown

- ID: M12128

- Name: Mycophenolic Acid

- Relevance: LOW

- As Found: Unknown

- ID: M18950

- Name: Tacrolimus

- Relevance: LOW

- As Found: Unknown

- ID: M21960

- Name: Sirolimus

- Relevance: HIGH

- As Found: Included

- ID: M28916

- Name: Angiotensin Receptor Antagonists

- Relevance: LOW

- As Found: Unknown

- ID: M10212

- Name: Immunosuppressive Agents

- Relevance: LOW

- As Found: Unknown

- ID: M30452

- Name: Calcineurin Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M4134

- Name: Angiotensin-Converting Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M353695

- Name: Temsirolimus

- Relevance: LOW

- As Found: Unknown

- ID: M2827

- Name: MTOR Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M4222

- Name: Anti-Bacterial Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4214

- Name: Anti-Infective Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4224

- Name: Antibiotics, Antitubercular

- Relevance: LOW

- As Found: Unknown

- ID: M6252

- Name: Clotrimazole

- Relevance: LOW

- As Found: Unknown

- ID: M11796

- Name: Miconazole

- Relevance: LOW

- As Found: Unknown

- ID: M4254

- Name: Antifungal Agents

- Relevance: LOW

- As Found: Unknown

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000020123

- Term: Sirolimus

### Misc Info Module

- Version Holder: 2024-05-24

## Results Section

### Adverse Events Module

**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

#### Event Groups

**Group ID:** EG000

**Title:** Control

**Deaths Num Affected:** 3

**Deaths Num At Risk:** 90

**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

**ID:** EG000

**Other Num Affected:** 58

**Other Num at Risk:** 90

**Serious Number Affected:** 42

**Serious Number At Risk:** 90

**Title:** Control

**Group ID:** EG001

**Title:** Transition to Sirolimus

**Deaths Num Affected:** 10

**Deaths Num At Risk:** 185

**Description:** Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus. Patients were followed for 24 months post randomization

**ID:** EG001

**Other Num Affected:** 135

**Other Num at Risk:** 185

**Serious Number Affected:** 117

**Serious Number At Risk:** 185

**Title:** Transition to Sirolimus

**Frequency Threshold:** 0

#### Other Events

**Term:** Infections

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** 

**Term:** Hyperlipidemia

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Cardiac disorders

**Source Vocabulary:** 

**Term:** Diabetes

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Endocrine disorders

**Source Vocabulary:** 

**Term:** BK viremia

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Renal and urinary disorders

**Source Vocabulary:** 

**Term:** BK nephropathy

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Renal and urinary disorders

**Source Vocabulary:** 

#### Serious Events

**Term:** Renal allograft loss

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Renal and urinary disorders

##### Stats

**Group ID:** EG000

**Num Affected:** 4

**Num At Risk:** 90

**Num Events:** 4

**Group ID:** EG001

**Num Affected:** 12

**Num At Risk:** 185

**Num Events:** 12

**Term:** Proteinuria

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Renal and urinary disorders

##### Stats

**Group ID:** EG000

**Num Affected:** 12

**Num At Risk:** 90

**Num Events:** 12

**Group ID:** EG001

**Num Affected:** 61

**Num At Risk:** 185

**Num Events:** 61

**Term:** Neutropenia

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Blood and lymphatic system disorders

##### Stats

**Group ID:** EG000

**Num Affected:** 22

**Num At Risk:** 90

**Num Events:** 22

**Group ID:** EG001

**Num Affected:** 35

**Num At Risk:** 185

**Num Events:** 35

**Term:** Malignancies

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps)

##### Stats

**Group ID:** EG000

**Num Affected:** 4

**Num At Risk:** 90

**Num Events:** 4

**Group ID:** EG001

**Num Affected:** 9

**Num At Risk:** 185

**Num Events:** 9

**Time Frame:** 24 months

## Results Section - Baseline Characteristics Module

### Denomination Counts

**Group ID:** BG000

**Value:** 90

**Group ID:** BG001

**Value:** 185

**Group ID:** BG002

**Value:** 275

**Units:** Participants

### Group

**ID:** BG000

**Title:** Control

**Description:** Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.

### Group

**ID:** BG001

**Title:** Transition to Sirolimus Group

**Description:** Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus

### Group

**ID:** BG002

**Title:** Total

**Description:** Total of all reporting groups

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 12.6

**Value:** 39.2

#### Measurement

**Group ID:** BG001

**Spread:** 12.5

**Value:** 38.8

#### Measurement

**Group ID:** BG002

**Spread:** 12.6

**Value:** 38.9

**Class Title:** Age in years

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 55

#### Measurement

**Group ID:** BG001

**Value:** 106

#### Measurement

**Group ID:** BG002

**Value:** 161

**Class Title:** Sex male

#### Measurement

**Group ID:** BG000

**Value:** 35

#### Measurement

**Group ID:** BG001

**Value:** 79

#### Measurement

**Group ID:** BG002

**Value:** 114

**Class Title:** Sex female

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 44

#### Measurement

**Group ID:** BG001

**Value:** 83

#### Measurement

**Group ID:** BG002

**Value:** 127

**Class Title:** white

#### Measurement

**Group ID:** BG000

**Value:** 24

#### Measurement

**Group ID:** BG001

**Value:** 37

#### Measurement

**Group ID:** BG002

**Value:** 61

**Class Title:** AA

#### Measurement

**Group ID:** BG000

**Value:** 17

#### Measurement

**Group ID:** BG001

**Value:** 45

#### Measurement

**Group ID:** BG002

**Value:** 62

**Class Title:** Hispanic

#### Measurement

**Group ID:** BG000

**Value:** 5

#### Measurement

**Group ID:** BG001

**Value:** 20

#### Measurement

**Group ID:** BG002

**Value:** 25

**Class Title:** other

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 90

#### Measurement

**Group ID:** BG001

**Value:** 185

#### Measurement

**Group ID:** BG002

**Value:** 275

**Class Title:** United States

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 1.7

**Value:** 3.9

#### Measurement

**Group ID:** BG001

**Spread:** 1.82

**Value:** 3.61

#### Measurement

**Group ID:** BG002

**Spread:** 1.8

**Value:** 3.8

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 63

#### Measurement

**Group ID:** BG001

**Value:** 130

#### Measurement

**Group ID:** BG002

**Value:** 193

**Category Title:** Living donors

#### Measurement

**Group ID:** BG000

**Value:** 27

#### Measurement

**Group ID:** BG001

**Value:** 55

#### Measurement

**Group ID:** BG002

**Value:** 82

**Category Title:** Cadaveric kidneys

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 14

#### Measurement

**Group ID:** BG001

**Value:** 24

#### Measurement

**Group ID:** BG002

**Value:** 38

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 26

#### Measurement

**Group ID:** BG001

**Value:** 69

#### Measurement

**Group ID:** BG002

**Value:** 95

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 76

#### Measurement

**Group ID:** BG001

**Value:** 158

#### Measurement

**Group ID:** BG002

**Value:** 234

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 10

#### Measurement

**Group ID:** BG001

**Value:** 31

#### Measurement

**Group ID:** BG002

**Value:** 41

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 9

#### Measurement

**Group ID:** BG001

**Value:** 29

#### Measurement

**Group ID:** BG002

**Value:** 38

**Class Title:** 

**Denomination Units Selected:** 

## Results Section - Baseline Characteristics Module

### Measure 1
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Age, Customized
**Unit of Measure:** years
### Measure 2
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Sex/Gender, Customized
**Unit of Measure:** Participants
### Measure 3
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Race/Ethnicity, Customized
**Unit of Measure:** Participants
### Measure 4
**Parameter Type:** NUMBER
**Title:** Region of Enrollment
**Unit of Measure:** participants
### Measure 5
**Description:** The number of human leukocyte antigens (HLAs) found on the cells of a donor organ but not found on the cells of the organ recipient
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** HLA mismatch
**Unit of Measure:** HLA antigens
### Measure 6
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Donor type
**Unit of Measure:** Participants
### Measure 7
**Description:** A panel-reactive antibody (PRA) is a group of antibodies in a test serum that are reactive against any of several known specific antigens in a panel of test cells or purified HLA antigens from cells. A panel-reactive antibody test (PRA test) is an immunologic test routinely performed by clinical laboratories on the blood of people awaiting organ transplantation.

This result is the number of participants on the study that had PRA \> 20% at the time of Transplantation
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** PRA >20%
**Unit of Measure:** Participants
### Measure 8
**Description:** Number of participants that were diagnosed with Diabetes at the time of Transplantation
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Diabetis mellitus
**Unit of Measure:** Participants
### Measure 9
**Description:** Number of participant with elevated blood pressure at the time of Transplantation
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Elevated blood pressure
**Unit of Measure:** Participants
### Measure 10
**Description:** Coronary artery disease (CAD) occurs when the arteries that supply blood to the heart become hardened and narrowed due to the buildup of cholesterol and other substances, known as plaque
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Coronary artery disease (CAD)
**Unit of Measure:** Participants
### Measure 11
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Smoking
**Unit of Measure:** Participants
**Population 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
## Results Section - More Information Module
### Certain Agreement
### Point of Contact
**Email:** l-gallon@northwestern.edu
**Organization:** Northwestern University
**Phone:** 3126954457
**Title:** Lorenzo Gallon, MD
## Results Section - Outcome Measures Module
### Outcome Measure 1
### Outcome Measure 2
### Outcome Measure 3
### Outcome Measure 4
### Outcome Measure 5
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 7
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 31
**Title:** 
#### Outcome Measure 2
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 20.4
- **Upper Limit:** 
- **Value:** 57.6
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 25.2
- **Upper Limit:** 
- **Value:** 58.4
**Title:** 
#### Outcome Measure 3
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 33
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 83
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 4
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 9
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 12
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 61
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 9
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 19
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 3
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 2
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 15
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 28
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 5
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 22
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 35
**Title:** 
#### Outcome Measure 4
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 4
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 12
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 3
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 10
**Title:** 
#### Outcome Measure 5
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 7.1
- **Upper Limit:** 
- **Value:** 75
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 10.8
- **Upper Limit:** 
- **Value:** 98
**Title:** 
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**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.
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Reporting Status:** POSTED
**Time Frame:** Assessed at 6 Months, 12 Months, 24 Months, months 24 reported
**Title:** Incidence of Acute Cellular Rejection
**Type:** PRIMARY
**Unit of Measure:** Participants
##### Group
**Description:** Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.
**ID:** OG000
**Title:** Control
##### Group
**Description:** Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus
**ID:** OG001
**Title:** Transition to Sirolimus Group
#### Outcome Measure 2
**Description:** Evaluate whether CI conversion (tacrolimus→sirolimus) contributes positively or negatively on the renal allograft function calculated with e-GFR and proteinuria
**Dispersion Type:** Standard Deviation
**Parameter Type:** MEAN
**Reporting Status:** POSTED
**Time Frame:** Assessed at 6 Months, 12 Months, 24 Months, months 24 reported
**Title:** Renal Allograft Function Calculated With e-GFR and Proteinuria
**Type:** SECONDARY
**Unit of Measure:** mL/min
##### Group
**Description:** Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.
**ID:** OG000
**Title:** Control
##### Group
**Description:** Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus
**ID:** OG001
**Title:** Transition to Sirolimus Group
#### Outcome Measure 3
**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).
**Parameter Type:** NUMBER
**Reporting Status:** POSTED
**Time Frame:** Assessed at 6 Months, 12 Months, 24 Months, months 24 reported
**Title:** Evaluate if CI Conversion Impacts on Lipid Profile, Incidence of Hypertension, Malignancies, and Opportunistic Infections and Post-transplant DM
**Type:** SECONDARY
**Unit of Measure:** number of incidents
##### Group
**Description:** Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.
**ID:** OG000
**Title:** Control
##### Group
**Description:** Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus
**ID:** OG001
**Title:** Transition to Sirolimus Group
#### Outcome Measure 4
**Description:** This study also reviews the impact of the immunosuppressive medications on patient and graft survival.
**Parameter Type:** NUMBER
**Reporting Status:** POSTED
**Time Frame:** Assessed at 6 Months, 12 Months, 24 Months, months 24 reported
**Title:** Patient and Graft Survival
**Type:** SECONDARY
**Unit of Measure:** number of incidents
##### Group
**Description:** Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.
**ID:** OG000
**Title:** Control
##### Group
**Description:** Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus
**ID:** OG001
**Title:** Transition to Sirolimus Group
#### Outcome Measure 5
**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).
**Dispersion Type:** Standard Deviation
**Parameter Type:** MEAN
**Reporting Status:** POSTED
**Time Frame:** Assessed at 6 Months, 12 Months, 24 Months, months 24 reported
**Title:** Percentage of Regulatory T Cells
**Type:** SECONDARY
**Unit of Measure:** % of Treg Cells
##### Group
**Description:** Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.
**ID:** OG000
**Title:** Control
##### Group
**Description:** Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus
**ID:** OG001
**Title:** Transition to Sirolimus Group
### Participant Flow Module
#### Group
**Description:** Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.
**ID:** FG000
**Title:** Control
#### Group
**Description:** Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus
**ID:** FG001
**Title:** Transition to Sirolimus Group
#### Period
**Title:** Overall Study
##### Milestone
**Type:** STARTED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 90
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 185
##### Milestone
**Type:** COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 90
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 185
##### Milestone
**Type:** NOT COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 0
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 0
**Pre-Assignment Details:** 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
**Has Results:** True