Randomized Conversion of Calcineurin-Inhibitors in Renal Allograft Recipients
NCT00866879
ABOUT THIS STUDY
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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.
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
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Descriptive Information | ||||
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Brief Title ICMJE | Randomized Conversion of Calcineurin-Inhibitors in Renal Allograft Recipients | |||
Official Title ICMJE | 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 | |||
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:
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 Type ICMJE | Interventional | |||
Study Phase ICMJE | Phase 4 | |||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Prevention | |||
Condition ICMJE | Renal Transplant Rejection | |||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. | ||||
Recruitment Information | ||||
Recruitment Status ICMJE | Completed | |||
Actual Enrollment ICMJE | 275 | |||
Original Estimated Enrollment ICMJE | 200 | |||
Actual Study Completion Date ICMJE | March 2019 | |||
Actual Primary Completion Date | December 2017 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 70 Years (Adult, Older Adult) | |||
Accepts Healthy Volunteers ICMJE | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | United States | |||
Removed Location Countries | ||||
Administrative Information | ||||
NCT Number ICMJE | NCT00866879 | |||
Other Study ID Numbers ICMJE | STU8308 0773-017 0468H1-4472 ( Other Identifier: Pfizer (Wyeth) ) | |||
Has Data Monitoring Committee | No | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement ICMJE | Not Provided | |||
Responsible Party | Lorenzo Gallon, Northwestern University | |||
Study Sponsor ICMJE | Northwestern University | |||
Collaborators ICMJE | Wyeth is now a wholly owned subsidiary of Pfizer | |||
Investigators ICMJE |
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PRS Account | Northwestern University | |||
Verification Date | June 2019 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |