Randomized Conversion of Calcineurin-Inhibitors in Renal Allograft Recipients
This study is currently recruiting participants.
Verified April 2013 by Northwestern University
Sponsor:
Northwestern University
Collaborator:
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
Lorenzo Gallon, Northwestern University
ClinicalTrials.gov Identifier:
NCT00866879
First received: March 19, 2009
Last updated: April 16, 2013
Last verified: April 2013
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Purpose
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 | Intervention | 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 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: 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 |
Resource links provided by NLM:
Further study details as provided by Northwestern University:
Primary Outcome Measures:
- To investigate the impact of CI conversion (tacrolimus→sirolimus) on the incidence of acute cellular rejection. [ Time Frame: 6 Months, 12 Months, 24 Months ] [ Designated as safety issue: Yes ]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:
- Evaluate whether CI conversion (tacrolimus→sirolimus) contributes positively or negatively on the renal allograft function calculated with e-GFR and proteinuria [ Time Frame: 6 Months, 12 Months, and 24 Months ] [ Designated as safety issue: Yes ]Previous chart reviews indicated a prednisone-free regiment (treatment) conversion from calcineurin inhibitors to sirolimus at 1 yr post-transplant did not show an increase in risk for acute rejection or graft loss. A trend towards a better Glomerular filtration rate (GFR) was noted after conversion from calcineurin inhibitors to sirolimus.
- Evaluate if CI conversion impacts on lipid profile, incidence of hypertension, malignancies, and opportunistic infections and post-transplant DM [ Time Frame: 6 Months, 12 Months, 24 Months ] [ Designated as safety issue: Yes ]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).
- Patient and graft survival [ Time Frame: 6 Months, 12 Months, 24 Months ] [ Designated as safety issue: Yes ]This study also reviews the impact of the immunosuppressive medications on patient and graft survival.
- Evaluate possible modifications of lymphocytes function before and after conversion (tacrolimus→sirolimus) [ Time Frame: Baseline pre-randomization labs, at 6, 12 and 24 Months ] [ Designated as safety issue: Yes ]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).
- Assess tubular toxicity by evaluating urinary biomarkers [ Time Frame: 6 Months, 12 Months, 24 Months ] [ Designated as safety issue: Yes ]Urine will be collected to assess tubular toxicity by evaluating urinary biomarkers.
| Estimated Enrollment: | 275 |
| Study Start Date: | June 2007 |
| Estimated Study Completion Date: | December 2015 |
| Estimated Primary Completion Date: | December 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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 ACEI and/or ARB level of renal allograft function-estimated GFR (e-GFR(12) using 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 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 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 Name: 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 ACEI and/or ARB level of renal allograft function-estimated GFR (e-GFR(12) using 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 CI free immunosuppression on gene expression profiles.
|
|
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
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years to 70 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Subjects should be adults ≥ 18- ≤ 70 years of age
- Subjects can be either gender or of any ethnic background
- Subjects should be single organ recipients (kidney only)
- Subjects must be able to understand the protocol and provide informed consent.
Exclusion Criteria:
- Subjects with ESRD secondary to primary FSGS (focal segmental glomerulonephritis).
- Inability to comply with study procedures
- Inability to sign the informed consent
- Subjects with a significant or active infection
- Subjects who are pregnant or nursing females
- Subjects with a history of severe hyperlipidemia not controlled with statins, patients with at total cholesterol of > 400 mg/dl
- Subjects with a platelet count <100,000mm3 WBC< 2,000mm3
- Subjects with severe proteinuria at the time of randomization (>2gm/day)
- Subjects with more then 2 episodes of acute cellular rejection post transplantation will be excluded from this study
- An estimated GFR<40 cc/min
- A history of malignancy during the post-transplant period (other than treated basal cell cancer and/or squamous cell cancer)
- 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
- A history of ACR during the most recent previous 3 months prior to randomization
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00866879
Contacts
| Contact: Farida Siddiqui, CCRP | 312-694-0242 | f-siddiqui@northwestern.edu |
Locations
| United States, Illinois | |
| Northwestern Memorial Hospital | Recruiting |
| 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 |
More Information
Publications:
| Responsible Party: | Lorenzo Gallon, Associate Professor, Northwestern University |
| ClinicalTrials.gov Identifier: | NCT00866879 History of Changes |
| Other Study ID Numbers: | STU8308 0773-017, 0468H1-4472 |
| Study First Received: | March 19, 2009 |
| Last Updated: | April 16, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Northwestern University:
|
Sirolimus Rapamune Immunosuppression Renal allograft function Lymphocytes function |
Additional relevant MeSH terms:
|
Sirolimus Everolimus Tacrolimus Antibiotics, Antineoplastic Antineoplastic Agents Therapeutic Uses Pharmacologic Actions |
Antifungal Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Anti-Bacterial Agents |
ClinicalTrials.gov processed this record on May 16, 2013