Renal Transplant RejectionPhase 4NCT00866879

Randomized Conversion of Calcineurin-Inhibitors in Renal Allograft Recipients

A Phase 4 study testing Sirolimus, Demographic Data, Medical History, and Donor Data and Blood Draws for Experimental Group in people with Renal Transplant Rejection, run by Northwestern University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Renal Transplant Rejection
What is being tested?: Sirolimus, Demographic Data, Medical History, and Donor Data and Blood Draws for Experimental Group
Type of treatment: Pill or oral medicine, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 275 participants
Where: 1 siteUnited States
Study dates: Jun 2007to Mar 2019
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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

Show all 13Show fewer

Subjects with a platelet count <100,000mm3 white blood cell (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 albumin-creatinine ratio (ACR) during the most recent previous 3 months prior to randomization

Trial locations and contacts

1 site in 1 country.

United States1 site

Northwestern Memorial Hospital
Chicago, Illinois, 60611

Other trials in United States

About this study

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

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.

Read the 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: Renal Transplant Rejection
Being tested: Sirolimus, Demographic Data, Medical History, and Donor Data, Blood Draws for Control Group, Blood Draws for Experimental Group, Donor Blood Draws
Keywords: Sirolimus, Rapamune, Immunosuppression, Renal allograft function, Lymphocytes function

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SirolimusDrug
Also called Rapamune
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.
Demographic Data, Medical History, and Donor DataOther
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.
Blood Draws for Control GroupProcedure or surgery
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.
Blood Draws for Experimental GroupProcedure or surgery
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.
Donor Blood DrawsProcedure or surgery
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.
Donor InformationOther
Donor age, cadaveric vs. living donor, and histocompatibility and cross match to recipient
Kidney BiopsyProcedure or surgery
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.

Study groups in NCT00866879
Study group	Role	What they receive
Control	Active comparator	Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus. Receives: Other: Demographic Data, Medical History, and Donor Data; Procedure: Blood Draws for Control Group; Procedure: Kidney Biopsy
Transition to Sirolimus Group	Experimental	Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus Receives: Drug: Sirolimus; Other: Demographic Data, Medical History, and Donor Data; Procedure: Blood Draws for Experimental Group; Procedure: Kidney Biopsy
Donors	Other	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. Receives: Procedure: Donor Blood Draws; Other: Donor Information

What is being measured

The primary outcome is the main question the study is designed to answer.

Incidence of Acute Cellular Rejection
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.
Measured: Assessed at 6 Months, 12 Months, 24 Months, months 24 reported

Secondary outcomes (4)

Renal Allograft Function Calculated With e-GFR and Proteinuria
Evaluate whether CI conversion (tacrolimus→sirolimus) contributes positively or negatively on the renal allograft function calculated with e-GFR and proteinuria
Measured: Assessed at 6 Months, 12 Months, 24 Months, months 24 reported
Evaluate if CI Conversion Impacts on Lipid Profile, Incidence of Hypertension, Malignancies, and Opportunistic Infections and Post-transplant DM
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).
Measured: Assessed at 6 Months, 12 Months, 24 Months, months 24 reported
Patient and Graft Survival
This study also reviews the impact of the immunosuppressive medications on patient and graft survival.
Measured: Assessed at 6 Months, 12 Months, 24 Months, months 24 reported
Percentage of Regulatory T Cells
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).
Measured: Assessed at 6 Months, 12 Months, 24 Months, months 24 reported

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2007Mar 2019

First posted23 Mar 2009 (estimated)
Study startJun 2007
Primary completionDec 2017
Study completionMar 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (12)Papers the sponsor has linked to this study.
Other trials for Renal Transplant RejectionStudies of the same condition, open and under way.
More trials run by Northwestern UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 275 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00866879
Sponsor's protocol ID: STU8308 0773-017
Other IDs: 0468H1-4472
Status last verified: Jun 2019
First submitted: 19 Mar 2009
Last updated: 28 Jun 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 12954741
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.
PubMed 12401874
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.
PubMed 11773892
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.
PubMed 9679823
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.
PubMed 9884274
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.
PubMed 9075835
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.
PubMed 6382005
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.
PubMed 8887265
Bennett WM. Insights into chronic cyclosporine nephrotoxicity. Int J Clin Pharmacol Ther. 1996 Nov;34(11):515-9.
PubMed 8937936
Myers BD. Cyclosporine nephrotoxicity. Kidney Int. 1986 Dec;30(6):964-74. doi: 10.1038/ki.1986.280. No abstract available.
PubMed 3546916
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.
PubMed 2240057
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.
PubMed 7861719

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Renal Transplant Rejection trials

Study at a glance

From the registry record, last updated by the sponsor on 28 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00866879
Acronym / sponsor ID: STU8308 0773-017
Conditions: Renal Transplant Rejection
Keywords: Sirolimus, Rapamune, Immunosuppression, Renal allograft function, Lymphocytes function
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 275 participants (actual)
Lead sponsor: Northwestern UniversityUniversity, hospital or other
Collaborators: Wyeth is now a wholly owned subsidiary of Pfizer
Study start: Jun 2007 (actual)
Primary completion: Dec 2017 (actual)
Study completion: Mar 2019 (actual)
First posted: 23 Mar 2009 (estimated)
Results: Posted 31 May 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Control	Active comparator	Other: Demographic Data, Medical History, and Donor Data, Procedure: Blood Draws for Control Group, Procedure: Kidney BiopsyGroup 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.
Transition to Sirolimus Group	Experimental	Drug: Sirolimus, Other: Demographic Data, Medical History, and Donor Data, Procedure: Blood Draws for Experimental Group, Procedure: Kidney BiopsyGroup 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus
Donors	Other	Procedure: Donor Blood Draws, Other: Donor InformationData 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.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (13 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SirolimusAlso: RapamuneSirolimus 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.	Drug	Transition to Sirolimus Group
Demographic Data, Medical History, and Donor DataAge 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.	Other	Control, Transition to Sirolimus Group
Blood Draws for Control GroupSubjects 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 or surgery	Control
Blood Draws for Experimental GroupThis 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 or surgery	Transition to Sirolimus Group
Donor Blood DrawsPeripheral 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.	Procedure or surgery	Donors
Donor InformationDonor age, cadaveric vs. living donor, and histocompatibility and cross match to recipient	Other	Donors
Kidney BiopsyKidney 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.	Procedure or surgery	Control, Transition to Sirolimus Group

Primary outcome

Incidence of Acute Cellular Rejection
Time frame: 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.

4 secondary outcomes

Renal Allograft Function Calculated With e-GFR and Proteinuria
Time frame: Assessed at 6 Months, 12 Months, 24 Months, months 24 reported
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
Patient and Graft Survival
Time frame: Assessed at 6 Months, 12 Months, 24 Months, months 24 reported
Percentage of Regulatory T Cells
Time frame: Assessed at 6 Months, 12 Months, 24 Months, months 24 reported

Results and safety

Results posted to the registry on 31 May 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Control	90	90
Transition to Sirolimus Group	185	185

Primary outcome: Incidence of Acute Cellular Rejection

Time frame: Assessed at 6 Months, 12 Months, 24 Months, months 24 reported. Count of participants. Unit: Participants

Measure	Control n = 90	Transition to Sirolimus Group n = 185
Value	7	31

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: 24 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Control	42 of 90 (46.7%)	58 of 90 (64.4%)	3 of 90
Transition to Sirolimus	117 of 185 (63.2%)	135 of 185 (73%)	10 of 185

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 12954741Ojo 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.
Background: PubMed 12401874Stoves 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.
Background: PubMed 11773892Gonwa 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.
Background: PubMed 9679823Fisher 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.
Background: PubMed 9884274Hornberger 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.
Background: PubMed 9075835Goldstein 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.
Background: PubMed 6382005Myers 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.
Background: PubMed 8887265Bennett 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.
Background: PubMed 8937936Bennett WM. Insights into chronic cyclosporine nephrotoxicity. Int J Clin Pharmacol Ther. 1996 Nov;34(11):515-9.
Background: PubMed 3546916Myers BD. Cyclosporine nephrotoxicity. Kidney Int. 1986 Dec;30(6):964-74. doi: 10.1038/ki.1986.280. No abstract available.
Background: PubMed 2240057Puschett 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.
Background: PubMed 7861719Young 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Lorenzo Gallon, MD principal investigator

Northwestern Univesity, Northwestern Memorial Hospital, Northwestern Medical Faculty Foundation

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Acute Cellular Rejection (time frame: Assessed at 6 Months, 12 Months, 24 Months, months 24 reported). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00866879, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2019.