End-stage Renal DiseasePhase 4NCT00556933

Improved Induction and Maintenance Immunosuppression in Kidney Transplantation

A Phase 4 study testing rabbit anti-thymocyte globulin - single dose, mycophenolate mofetil and rabbit anti-thymocyte globulin - 4 doses in people with End-stage Renal Disease, run by University of Nebraska 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 65 years
Conditions the study is for: End-stage Renal Disease
What is being tested?: rabbit anti-thymocyte globulin - single dose, mycophenolate mofetil and rabbit anti-thymocyte globulin - 4 doses
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 180 participants
Where: 1 siteUnited States
Study dates: 1 Apr 2004to 1 Jun 2011
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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Primary renal transplant recipient for end-stage renal disease

Who cannot join

Recipient age < 18 years or > 65 years
Previous history of CMV disease
Hepatitis B and C recipients
Primary disease states that require steroids for immunosuppression
Re-transplant with immunological cause of renal or pancreas loss
Non heart beating donors

Show all 14Show fewer

Recipient of pediatric en bloc kidneys
Recipient with a Panel Reactive Antibody (PRA) score >75%
Patients who have received 3 or more prior transplants, excluding pancreas
Patients who are past recipients of other solid organ transplants
Previous history of BK virus
Previous treatment with Thymoglobulin
Allergy to rabbits
Simultaneous Kidney/Pancreas transplantation

Trial locations and contacts

1 site in 1 country.

United States1 site

Unversity of Nebraska Medical Center
Omaha, Nebraska, 68198

Other trials in United States

About this study

Official title: Prospective, Randomized 2 x 2 Factorial Trial of Rabbit Anti-thymocyte Globulin Induction (Single vs. Alternate Day Administration) at Renal Transplantation, With Delayed Calcineurin-inhibitor Withdrawal vs. Minimization

This 2 x 2 sequential factorial study evaluates two potential improvements to the standard immunosuppression regimen used at the investigators' institution to prevent rejection of transplanted kidneys. These two potential improvements are each applied in sequence to half of the study patients, creating 4 study arms; the other half receive the standard treatment. The two potential improvements are:

Administering the immunosuppression induction agent rATG ("rabbit anti-thymocyte globulin") in a single dose at the time of transplantation, instead of in the usual series of 4 smaller doses over 6 days.
After 6 months, modifying the maintenance immunosuppression used to prevent rejection by replacing the drug tacrolimus with mycophenolate mofetil (MMF).

The two interventions, spaced sequentially six months apart, enable independent analysis of the two treatments so long as it can be shown that there is no synergistic interaction between them.

Read the detailed description

The two treatment innovations in this study of immunosuppression in kidney transplantation are aimed at making the transplanted kidney function sooner and last longer than is usual with standard immunosuppression regimens, but without increasing the likelihood of rejection.

The first innovation, delivering the induction agent rATG in a single large dose rather than as a series of smaller doses over 6-8 days, is expected to produce better graft function right away, possibly by reducing some of the injury to the kidney that accompanies the restoration of blood flow during transplantation ("reperfusion injury"). Some evidence has been developed by investigators elsewhere to suggest this will happen.

The second innovation, replacing tacrolimus with MMF after 6 months, is intended to eliminate a well-established major cause of ongoing toxic damage to the kidney. While tacrolimus does a good job of preventing rejection, the cost in continuing toxic injury to the kidney is high, leading inevitably to eventual graft failure, the inability of the transplanted kidney to continue filtering the blood and making adequate volumes of high-quality urine.

Conditions: End-stage Renal Disease
Being tested: rabbit anti-thymocyte globulin - single dose, mycophenolate mofetil, rabbit anti-thymocyte globulin - 4 doses, sirolimus, tacrolimus
Keywords: Induction, rATG, Calcineurin-inhibitor withdrawal
Medical subject headings: Kidney Failure, Chronic

What participants receive

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

rabbit anti-thymocyte globulin - single doseDrug
Also called Thymoglobulin, rATG
A single 6 mg/kg dose of rATG administered intravenously over 24 hours, beginning before kidney transplantation. Administration of the drug is begun as early as practical, usually after general anesthesia has been established but before surgery has started. The rATG is therefore administered for about two hours before blood flow is restored to the kidney undergoing transplantation.
mycophenolate mofetilDrug
Also called CellCept, MMF, mycophenolic acid, Myfortic
Patients are switched approximately 6 months after kidney transplantation from maintenance immunosuppression with tacrolimus and sirolimus to maintenance with mycophenolate mofetil and sirolimus. The drug is administered orally, taken daily, with dose adjusted in proportion to measured blood levels, and is required indefinitely to prevent rejection of the transplanted kidney.
rabbit anti-thymocyte globulin - 4 dosesDrug
Also called Thymoglobulin
6 mg/kg rabbit anti-thymocyte globulin delivered in 4 doses of 1.5 mg/kg each, the first administered at the time of kidney transplantation. Subsequent doses are administered on days 2, 4, and 6.
sirolimusDrug
Also called Rapamune, rapamycin
Oral maintenance immunosuppressant administered daily, dose adjusted according to measured serum trough levels, continued indefinitely to prevent kidney rejection
tacrolimusDrug
Also called FK506, ProGraf
Oral maintenance immunosuppressant, taken daily, dose adjusted to maintain target blood trough levels, required indefinitely to prevent kidney rejection.

Study groups in NCT00556933
Study group	Role	What they receive
Group 1	Experimental	Kidney transplant recipients given a single large dose of rabbit anti-thymocyte globulin (rATG) and maintained on tacrolimus and sirolimus for chronic immunosuppression. Receives: Drug: rabbit anti-thymocyte globulin - single dose; Drug: sirolimus; Drug: tacrolimus
Group 2	Experimental	Kidney transplant recipients given 4 small doses of rabbit anti-thymocyte globulin (rATG) and maintained on tacrolimus and sirolimus for chronic immunosuppression. Receives: Drug: rabbit anti-thymocyte globulin - 4 doses; Drug: sirolimus; Drug: tacrolimus
Group 3	Experimental	Kidney transplant recipients given a single large dose of rabbit anti-thymocyte globulin (rATG) and maintained on tacrolimus and sirolimus for chronic immunosuppression until tacrolimus is replaced with mycophenolate mofetil after about 6 months. Receives: Drug: rabbit anti-thymocyte globulin - single dose; Drug: mycophenolate mofetil; Drug: sirolimus; Drug: tacrolimus
Group 4	Experimental	Kidney transplant recipients given 4 small doses of rabbit anti-thymocyte globulin (rATG) and maintained on tacrolimus and sirolimus for chronic immunosuppression until tacrolimus is replaced with mycophenolate mofetil after about 6 months. Receives: Drug: mycophenolate mofetil; Drug: rabbit anti-thymocyte globulin - 4 doses; Drug: sirolimus; Drug: tacrolimus

What is being measured

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

Chronic Allograft Nephropathy (Cumulative Calcineurin-inhibitor Nephrotoxicity/Transplant Nephropathy) Per Protocol Surveillance Kidney Biopsies (Banff Grading Criteria).
Protocol kidney biopsies collected at approximately 12 and 24 months were scored by a transplant renal pathologist blinded to treatment group assignment for evidence of rejection, BK virus nephropathy, antibody-mediated rejection, recurrent disease, inflammation, and Banff 2005 categories of chronic renal injury. Chronic injury categories were arteriolar hyaline thickening (ah), allograft glomerulopathy (cg), interstitial fibrosis (ci), tubular atrophy (ct), and vascular fibrous intimal thickening (cv). Severity scores within each category could be 0 (<5%; none or minimal), 1 (>5% - <25%; mild), 2 (>25% - <50%, moderate), or 3 (>50%, severe). The proportions of patients in each severity grade (0, 1, 2, and 3) for both the individual categories and a composite were compared using Fisher's exact test.
Measured: Two years
Average of Renal Function
Calculated Glomerular Filtration Rate (GFR) by using the abbreviated MDRD (aMDRD) formula and patient serum creatinine and demographic data; averaged values from months four through 24.
Measured: Two years

Secondary outcomes (10)

Safety Profile
Number of events: cytomegalovirus (CMV) disease, opportunistic infections (bacteremia, abscess, pneumonia, fungal), Post-transplantation Lymphoproliferative Disorder (PTLD), wound healing problems within 30 days, and lymphoceles.
Measured: Two years
Requirement for Additional Immunosuppression (Such as Corticosteroids, Antimetabolites or Other Immunosuppressive Agents)
Measured: Two years
Acute Rejection Per Kidney Biopsy (Banff Grading Criteria)
Measured: Two years
Acute Tubular Necrosis (ATN) Rate, Defined as the Requirement for Dialysis Within 7 Days Post-transplantation.
Measured: Seven days
Graft Survival
Graft failure = permanent return of patient to dialysis.
Measured: Two years
Patient Survival
Measured: Two years
Lymphoid Cell Sub-type CD3 Absolute Numbers
Measured: One year
New-onset Polyomavirus (BK Virus) Disease Per Kidney Biopsy
Measured: Two years
New-onset Diabetes and Hyperglycemia After Transplantation (NODAT)
Measured: Six months
Ratio of CD4/CD8 Lymphoid Cells
Measured: One year

Timeline

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

1 Apr 20041 Jun 2011

First posted12 Nov 2007 (estimated)
Study start1 Apr 2004
Primary completion1 Apr 2011
Study completion1 Jun 2011

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 (8)Papers the sponsor has linked to this study.
Other trials for End-stage Renal DiseaseStudies of the same condition, open and under way.
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: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: None (open label)
Enrolment: 180 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00556933
Sponsor's protocol ID: 0286-03-FB
Status last verified: Aug 2023
First submitted: 9 Nov 2007
Last updated: 18 Sep 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Miles CD, Skorupa JY, Sandoz JP, Rigley TH, Nielsen KJ, Stevens RB. Albuminuria after renal transplantation: maintenance with sirolimus/low-dose tacrolimus vs. mycophenolate mofetil/high-dose tacrolimus. Clin Transplant. 2011 Nov-Dec;25(6):898-904. doi: 10.1111/j.1399-0012.2010.01353.x. Epub 2010 Nov 16.
PubMed 21077952
Stevens RB. Modern approaches to combining sirolimus with calcineurin inhibitors. Transplant Proc. 2008 Dec;40(10 Suppl):S21-4. doi: 10.1016/j.transproceed.2008.10.012.
PubMed 19100901
Sulanc E, Lane JT, Puumala SE, Groggel GC, Wrenshall LE, Stevens RB. New-onset diabetes after kidney transplantation: an application of 2003 International Guidelines. Transplantation. 2005 Oct 15;80(7):945-52. doi: 10.1097/01.tp.0000176482.63122.03.
PubMed 16249743
Stevens RB, Foster KW, Miles CD, Lane JT, Kalil AC, Florescu DF, Sandoz JP, Rigley TH, Nielsen KJ, Skorupa JY, Kellogg AM, Malik T, Wrenshall LE. A randomized 2x2 factorial trial, part 1: single-dose rabbit antithymocyte globulin induction may improve renal transplantation outcomes. Transplantation. 2015 Jan;99(1):197-209. doi: 10.1097/TP.0000000000000250.
PubMed 25083614
Stevens RB, Lane JT, Boerner BP, Miles CD, Rigley TH, Sandoz JP, Nielsen KJ, Skorupa JY, Skorupa AJ, Kaplan B, Wrenshall LE. Single-dose rATG induction at renal transplantation: superior renal function and glucoregulation with less hypomagnesemia. Clin Transplant. 2012 Jan-Feb;26(1):123-32. doi: 10.1111/j.1399-0012.2011.01425.x. Epub 2011 Mar 14.
PubMed 21401720
Snow MH, Cannella AC, Stevens RB, Mikuls TR. Presumptive serum sickness as a complication of rabbit-derived antithymocyte globulin immunosuppression. Arthritis Rheum. 2009 Sep 15;61(9):1271-4. doi: 10.1002/art.24788. No abstract available.
PubMed 19714613
Stevens RB, Mercer DF, Grant WJ, Freifeld AG, Lane JT, Groggel GC, Rigley TH, Nielsen KJ, Henning ME, Skorupa JY, Skorupa AJ, Christensen KA, Sandoz JP, Kellogg AM, Langnas AN, Wrenshall LE. Randomized trial of single-dose versus divided-dose rabbit anti-thymocyte globulin induction in renal transplantation: an interim report. Transplantation. 2008 May 27;85(10):1391-9. doi: 10.1097/TP.0b013e3181722fad.
PubMed 18497677
Stevens RB, Foster KW, Miles CD, Kalil AC, Florescu DF, Sandoz JP, Rigley TH, Malik T, Wrenshall LE. A Randomized 2x2 Factorial Clinical Trial of Renal Transplantation: Steroid-Free Maintenance Immunosuppression with Calcineurin Inhibitor Withdrawal after Six Months Associates with Improved Renal Function and Reduced Chronic Histopathology. PLoS One. 2015 Oct 14;10(10):e0139247. doi: 10.1371/journal.pone.0139247. eCollection 2015.
PubMed 26465152

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?

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Study at a glance

From the registry record, last updated by the sponsor on 18 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Prospective, Randomized 2 x 2 Factorial Trial of Rabbit Anti-thymocyte Globulin Induction (Single vs. Alternate Day Administration) at Renal Transplantation, With Delayed Calcineurin-inhibitor Withdrawal vs. Minimization
ClinicalTrials.gov ID: NCT00556933
Acronym / sponsor ID: 0286-03-FB
Conditions: End-stage Renal Disease
Keywords: Induction, rATG, Calcineurin-inhibitor withdrawal
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 180 participants (actual)
Lead sponsor: University of NebraskaUniversity, hospital or other
Collaborators: Genzyme, a Sanofi Company
Study start: 1 Apr 2004 (actual)
Primary completion: 1 Apr 2011 (actual)
Study completion: 1 Jun 2011 (actual)
First posted: 12 Nov 2007 (estimated)
Results: Posted 2 Mar 2015

Clinical summary

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

Administering the immunosuppression induction agent rATG ("rabbit anti-thymocyte globulin") in a single dose at the time of transplantation, instead of in the usual series of 4 smaller doses over 6 days.
After 6 months, modifying the maintenance immunosuppression used to prevent rejection by replacing the drug tacrolimus with mycophenolate mofetil (MMF).

The two interventions, spaced sequentially six months apart, enable independent analysis of the two treatments so long as it can be shown that there is no synergistic interaction between them.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Group 1	Experimental	Drug: rabbit anti-thymocyte globulin - single dose, Drug: sirolimus, Drug: tacrolimusKidney transplant recipients given a single large dose of rabbit anti-thymocyte globulin (rATG) and maintained on tacrolimus and sirolimus for chronic immunosuppression.
Group 2	Experimental	Drug: rabbit anti-thymocyte globulin - 4 doses, Drug: sirolimus, Drug: tacrolimusKidney transplant recipients given 4 small doses of rabbit anti-thymocyte globulin (rATG) and maintained on tacrolimus and sirolimus for chronic immunosuppression.
Group 3	Experimental	Drug: rabbit anti-thymocyte globulin - single dose, Drug: mycophenolate mofetil, Drug: sirolimus, Drug: tacrolimusKidney transplant recipients given a single large dose of rabbit anti-thymocyte globulin (rATG) and maintained on tacrolimus and sirolimus for chronic immunosuppression until tacrolimus is replaced with mycophenolate mofetil after about 6 months.
Group 4	Experimental	Drug: mycophenolate mofetil, Drug: rabbit anti-thymocyte globulin - 4 doses, Drug: sirolimus, Drug: tacrolimusKidney transplant recipients given 4 small doses of rabbit anti-thymocyte globulin (rATG) and maintained on tacrolimus and sirolimus for chronic immunosuppression until tacrolimus is replaced with mycophenolate mofetil after about 6 months.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

Primary renal transplant recipient for end-stage renal disease

Key exclusion criteria (14 listed)

Recipient age < 18 years or > 65 years
Previous history of CMV disease
Hepatitis B and C recipients
Primary disease states that require steroids for immunosuppression
Re-transplant with immunological cause of renal or pancreas loss

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
rabbit anti-thymocyte globulin - single doseAlso: Thymoglobulin, rATGA single 6 mg/kg dose of rATG administered intravenously over 24 hours, beginning before kidney transplantation. Administration of the drug is begun as early as practical, usually after general anesthesia has been established but before surgery has started. The rATG is therefore administered for about two hours before blood flow is restored to the kidney undergoing transplantation.	Drug	Group 1, Group 3
mycophenolate mofetilAlso: CellCept, MMF, mycophenolic acid, MyforticPatients are switched approximately 6 months after kidney transplantation from maintenance immunosuppression with tacrolimus and sirolimus to maintenance with mycophenolate mofetil and sirolimus. The drug is administered orally, taken daily, with dose adjusted in proportion to measured blood levels, and is required indefinitely to prevent rejection of the transplanted kidney.	Drug	Group 3, Group 4
rabbit anti-thymocyte globulin - 4 dosesAlso: Thymoglobulin6 mg/kg rabbit anti-thymocyte globulin delivered in 4 doses of 1.5 mg/kg each, the first administered at the time of kidney transplantation. Subsequent doses are administered on days 2, 4, and 6.	Drug	Group 2, Group 4
sirolimusAlso: Rapamune, rapamycinOral maintenance immunosuppressant administered daily, dose adjusted according to measured serum trough levels, continued indefinitely to prevent kidney rejection	Drug	Group 1, Group 2, Group 3, Group 4
tacrolimusAlso: FK506, ProGrafOral maintenance immunosuppressant, taken daily, dose adjusted to maintain target blood trough levels, required indefinitely to prevent kidney rejection.	Drug	Group 1, Group 2, Group 3, Group 4

Primary outcome

Chronic Allograft Nephropathy (Cumulative Calcineurin-inhibitor Nephrotoxicity/Transplant Nephropathy) Per Protocol Surveillance Kidney Biopsies (Banff Grading Criteria).
Time frame: Two years
Protocol kidney biopsies collected at approximately 12 and 24 months were scored by a transplant renal pathologist blinded to treatment group assignment for evidence of rejection, BK virus nephropathy, antibody-mediated rejection, recurrent disease, inflammation, and Banff 2005 categories of chronic renal injury. Chronic injury categories were arteriolar hyaline thickening (ah), allograft glomerulopathy (cg), interstitial fibrosis (ci), tubular atrophy (ct), and vascular fibrous intimal thickening (cv). Severity scores within each category could be 0 (<5%; none or minimal), 1 (>5% - <25%; mild), 2 (>25% - <50%, moderate), or 3 (>50%, severe). The proportions of patients in each severity grade (0, 1, 2, and 3) for both the individual categories and a composite were compared using Fisher's exact test.
Average of Renal Function
Time frame: Two years
Calculated Glomerular Filtration Rate (GFR) by using the abbreviated MDRD (aMDRD) formula and patient serum creatinine and demographic data; averaged values from months four through 24.

10 secondary outcomes

Safety Profile
Time frame: Two years
Requirement for Additional Immunosuppression (Such as Corticosteroids, Antimetabolites or Other Immunosuppressive Agents)
Time frame: Two years
Acute Rejection Per Kidney Biopsy (Banff Grading Criteria)
Time frame: Two years
Acute Tubular Necrosis (ATN) Rate, Defined as the Requirement for Dialysis Within 7 Days Post-transplantation.
Time frame: Seven days
Graft Survival
Time frame: Two years
Patient Survival
Time frame: Two years
Lymphoid Cell Sub-type CD3 Absolute Numbers
Time frame: One year
New-onset Polyomavirus (BK Virus) Disease Per Kidney Biopsy
Time frame: Two years
New-onset Diabetes and Hyperglycemia After Transplantation (NODAT)
Time frame: Six months
Ratio of CD4/CD8 Lymphoid Cells
Time frame: One year

Results and safety

Results posted to the registry on 2 Mar 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Single Dose rATG (6 mg/kg x 1) and Tacrolimus/Sirolimus	45	43
Divided-dose rATG (1.5mg/kg x 4) and Tacrolimus/Sirolimus	45	37
Single-dose rATG (6mg/kg ) and Sirolimus/Mycophenolate Mofetil	45	39
Divided-dose rATG (1.5mg/kgx4),Sirolimus/Mycophenolate Mofetil	45	43

Primary outcome: Chronic Allograft Nephropathy (Cumulative Calcineurin-inhibitor Nephrotoxicity/Transplant Nephropathy) Per Protocol Surveillance Kidney Biopsies (Banff Grading Criteria).

Time frame: Two years. Number. Unit: percentage of participants

Measure	Single Dose rATG (6 mg/kg x 1) and Tacrolimus/Sirolimus n = 36	Divided-dose rATG (1.5mg/kg x 4) and Tacrolimus/Sirolimus n = 29	Single-dose rATG (6mg/kg ) and Sirolimus/Mycophenolate Mofetil n = 28	Divided-dose rATG(6mg/kg ) and Sirolimus/Mycophenolate Mofetil n = 29
Banff histopathology cumulative grade = 0	43	40	53	51
Banff histopathology cumulative grade = 1	37	46	45	41
Banff histopathology cumulative grade = 2	16	9	2	7
Banff histopathology cumulative grade = 3	4	6	0	1

Single Dose rATG (6 mg/kg x 1) and Tacrolimus/Sirolimus vs Divided-dose rATG (1.5mg/kg x 4) and Tacrolimus/Sirolimus vs Single-dose rATG (6mg/kg ) and Sirolimus/Mycophenolate Mofetil vs Divided-dose rATG(6mg/kg ) and Sirolimus/Mycophenolate Mofetil: p = 0.0004, Chi-squared

Primary outcome: Average of Renal Function

Time frame: Two years. Mean (Standard Deviation). Unit: ml/min/1.73m2

Measure	Single Dose rATG (6 mg/kg x 1) and Tacrolimus/Sirolimus n = 43	Divided-dose rATG (1.5mg/kg x 4) and Tacrolimus/Sirolimus n = 38	Single-dose rATG (6mg/kg ) and Sirolimus/Mycophenolate Mofetil n = 42	Divided-dose rATG(6mg/kg ) and Sirolimus/Mycophenolate Mofetil n = 44
Average GFR, months 1-3	50.4 (16.0)	50.1 (12.5)	53.6 (14.4)	50.4 (17.0)
Average GFR, months 4-6	57.3 (17.6)	57.3 (12.5)	60.2 (15.6)	54.8 (13.2)
Average GFR, months 7-9	54.8 (16.5)	55.0 (11.8)	61.0 (15.8)	55.8 (13.2)
Average GFR, months 10-12	55.8 (16.6)	55.6 (12.1)	57.4 (16.7)	56.6 (14.4)
Average GFR, months 13-15	56.8 (19.2)	57.3 (14.3)	61.8 (15.4)	58.5 (16.6)
Average GFR, months 16-18	57.6 (20.9)	56.3 (14.8)	62.3 (17.6)	56.6 (18.4)
Average GFR, months 19-21	56.6 (20.0)	54.8 (17.3)	60.2 (14.7)	56.8 (18.9)
Average GFR, months 22-24	56.9 (21.9)	57.0 (16.2)	62.9 (18.6)	57.6 (17.7)

Single Dose rATG (6 mg/kg x 1) and Tacrolimus/Sirolimus vs Divided-dose rATG (1.5mg/kg x 4) and Tacrolimus/Sirolimus vs Single-dose rATG (6mg/kg ) and Sirolimus/Mycophenolate Mofetil vs Divided-dose rATG(6mg/kg ) and Sirolimus/Mycophenolate Mofetil: p = 0.45, General Linear Model

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to two years.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group 1	9 of 44 (20.5%)	12 of 44 (27.3%)	Not reported
Group 2	15 of 44 (34.1%)	12 of 44 (27.3%)	Not reported
Group 3	18 of 45 (40%)	11 of 45 (24.4%)	Not reported
Group 4	21 of 45 (46.7%)	8 of 45 (17.8%)	Not reported

Limitations and caveats (from the sponsor): The trial is designed for analysis as 1st, rATG dosing, and 2nd, CNI withdrawal status. Results published as analysis of 2 induction protocols followed by analysis of 2 CNI maintenance regimens. Potential limitations = single-center \& non-blinded.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 21077952Miles CD, Skorupa JY, Sandoz JP, Rigley TH, Nielsen KJ, Stevens RB. Albuminuria after renal transplantation: maintenance with sirolimus/low-dose tacrolimus vs. mycophenolate mofetil/high-dose tacrolimus. Clin Transplant. 2011 Nov-Dec;25(6):898-904. doi: 10.1111/j.1399-0012.2010.01353.x. Epub 2010 Nov 16.
Background: PubMed 19100901Stevens RB. Modern approaches to combining sirolimus with calcineurin inhibitors. Transplant Proc. 2008 Dec;40(10 Suppl):S21-4. doi: 10.1016/j.transproceed.2008.10.012.
Background: PubMed 16249743Sulanc E, Lane JT, Puumala SE, Groggel GC, Wrenshall LE, Stevens RB. New-onset diabetes after kidney transplantation: an application of 2003 International Guidelines. Transplantation. 2005 Oct 15;80(7):945-52. doi: 10.1097/01.tp.0000176482.63122.03.
Results publication: PubMed 25083614Stevens RB, Foster KW, Miles CD, Lane JT, Kalil AC, Florescu DF, Sandoz JP, Rigley TH, Nielsen KJ, Skorupa JY, Kellogg AM, Malik T, Wrenshall LE. A randomized 2x2 factorial trial, part 1: single-dose rabbit antithymocyte globulin induction may improve renal transplantation outcomes. Transplantation. 2015 Jan;99(1):197-209. doi: 10.1097/TP.0000000000000250.
Results publication: PubMed 21401720Stevens RB, Lane JT, Boerner BP, Miles CD, Rigley TH, Sandoz JP, Nielsen KJ, Skorupa JY, Skorupa AJ, Kaplan B, Wrenshall LE. Single-dose rATG induction at renal transplantation: superior renal function and glucoregulation with less hypomagnesemia. Clin Transplant. 2012 Jan-Feb;26(1):123-32. doi: 10.1111/j.1399-0012.2011.01425.x. Epub 2011 Mar 14.
Results publication: PubMed 19714613Snow MH, Cannella AC, Stevens RB, Mikuls TR. Presumptive serum sickness as a complication of rabbit-derived antithymocyte globulin immunosuppression. Arthritis Rheum. 2009 Sep 15;61(9):1271-4. doi: 10.1002/art.24788. No abstract available.
Results publication: PubMed 18497677Stevens RB, Mercer DF, Grant WJ, Freifeld AG, Lane JT, Groggel GC, Rigley TH, Nielsen KJ, Henning ME, Skorupa JY, Skorupa AJ, Christensen KA, Sandoz JP, Kellogg AM, Langnas AN, Wrenshall LE. Randomized trial of single-dose versus divided-dose rabbit anti-thymocyte globulin induction in renal transplantation: an interim report. Transplantation. 2008 May 27;85(10):1391-9. doi: 10.1097/TP.0b013e3181722fad.
Derived from this study: PubMed 26465152Stevens RB, Foster KW, Miles CD, Kalil AC, Florescu DF, Sandoz JP, Rigley TH, Malik T, Wrenshall LE. A Randomized 2x2 Factorial Clinical Trial of Renal Transplantation: Steroid-Free Maintenance Immunosuppression with Calcineurin Inhibitor Withdrawal after Six Months Associates with Improved Renal Function and Reduced Chronic Histopathology. PLoS One. 2015 Oct 14;10(10):e0139247. doi: 10.1371/journal.pone.0139247. eCollection 2015.

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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.

R. Brian Stevens, MD, PhD study director

Wright State University Boonshoft School of Medicine, Dayton, OH

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 1 inclusion and 14 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 18 Sep 2023. 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 2 Mar 2015). 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?

Chronic Allograft Nephropathy (Cumulative Calcineurin-inhibitor Nephrotoxicity/Transplant Nephropathy) Per Protocol Surveillance Kidney Biopsies (Banff Grading Criteria). (time frame: Two years). The study lists 2 primary outcomes in all. 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 NCT00556933, which also lists 8 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 18 Sep 2023.