Phase 4 N=180 Randomized Treatment

Improved Induction and Maintenance Immunosuppression in Kidney Transplantation

End-stage Renal Disease

Bottom Line

View on ClinicalTrials.gov: NCT00556933 ↗

Enrolled (actual)

180

Serious AEs

35.4%

Results posted

Mar 2015

Primary outcome: Primary: Chronic Allograft Nephropathy (Cumulative Calcineurin-inhibitor Nephrotoxicity/Transplant Nephropathy) Per Protocol Surveillance Kidney Biopsies (Banff Grading Criteria). — 43; 40; 53; 51 percentage of participants — p=0.0004

Study Design & Population

Study type: Interventional
Phase: Phase 4
Interventions: rabbit anti-thymocyte globulin - single dose (Drug); mycophenolate mofetil (Drug); rabbit anti-thymocyte globulin - 4 doses (Drug); sirolimus (Drug); tacrolimus (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: University of Nebraska
Primary completion: Apr 2011

Outcome Measures

Outcome	Result	p-value
PRIMARY Chronic Allograft Nephropathy (Cumulative Calcineurin-inhibitor Nephrotoxicity/Transplant Nephropathy) Per Protocol Surveillance Kidney Biopsies (Banff Grading Criteria).	43; 40; 53; 51; 37; 46	0.0004 sig
PRIMARY Average of Renal Function	50.4; 50.1; 53.6; 50.4; 57.3; 57.3	0.45
SECONDARY Safety Profile	11; 14; 10; 17	0.53
SECONDARY Requirement for Additional Immunosuppression (Such as Corticosteroids, Antimetabolites or Other Immunosuppressive Agents)	7; 5; 6; 11	0.463
SECONDARY Acute Rejection Per Kidney Biopsy (Banff Grading Criteria)	7; 4; 8; 9	0.67
SECONDARY Acute Tubular Necrosis (ATN) Rate, Defined as the Requirement for Dialysis Within 7 Days Post-transplantation.	3; 1; 6; 2	0.193
SECONDARY Graft Survival	0; 1; 2; 0	0.422
SECONDARY Patient Survival	0; 1; 0; 1	0.871
SECONDARY Lymphoid Cell Sub-type CD3 Absolute Numbers	446; 375; 392; 266	0.068
SECONDARY New-onset Polyomavirus (BK Virus) Disease Per Kidney Biopsy	1; 2; 0; 2	0.67
SECONDARY New-onset Diabetes and Hyperglycemia After Transplantation (NODAT)	10; 7; 5; 12	0.21
SECONDARY Ratio of CD4/CD8 Lymphoid Cells	0.84; 0.84; 0.98; 1.01	0.40

Summary

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: 1. 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. 2. 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.

Eligibility Criteria

Inclusion Criteria

Primary renal transplant recipient for end-stage renal disease

Exclusion Criteria

Recipient age 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
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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00556933). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.