Clinical trial NCT00275509: Induction Therapy Study in Live Donor Kidney Transplant Recipients With a Positive Crossmatch
Official title: Open Label Randomized Study of Thymoglobulin Versus Daclizumab Induction Therapies for the Reduction of Acute Rejection in Live Donor Kidney Transplant Recipients With a Positive Crossmatch
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Kidney Failure, Chronic
Keywords: kidney
transplantation
positive crossmatch
antibody mediated rejection
rejection
induction
therapy
trial
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2006-01-12
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine whether the anti-T cell antibody, Thymoglobulin is a more effective induction medication than the anti-IL-2R inhibitor daclizumab, in kidney transplant recipients who have a positive crossmatch with their live donor.

Detailed description: Kidney transplantation is widely recognized as the optimal therapy for the management of end-stage renal disease. Presently, the deceased donor kidney waiting list has expanded disproportionately with the number of transplant procedures that are performed in the United States. To further compound this problem, as many as 1/3 of the patients on this list are highly sensitized against a broad range of potential donors.

In order to address this problem, we developed an antibody depletion protocol that permits transplantation in patients who have a positive crossmatch with their live donor. The protocol consists of standard immunosuppressant therapy, plasmapheresis, and intravenous immunoglobulin infusion. We have successfully performed transplantation in over 100 such patients with low complication rates.

Because these patients have been exposed to their donor's human leukocyte antigen (HLA) they are at high risk for both acute cellular and acute antibody-mediated rejection. This intent of this prospective, randomized, open-label trial is to determine whether induction therapy (i.e. therapy given at the time of transplantation for prophylaxis) with Thymoglobulin is associated with a lower 6-month incidence of acute cellular and antibody-mediated rejection than with our standard therapy, daclizumab.

Eligibility criteria: Inclusion Criteria:

* Adult (18 years or older)
* End-stage renal disease
* Identified to have positive lymphocytotoxic crossmatch or flow cytometric crossmatch with live donor

Exclusion Criteria:

* Deceased donor recipients
* Pregnancy
* Active infection
* History of cancer within the past two years (with the exception of non-melanomatous skin cancer)
* History of heparin induced thrombocytopenia
* Medical contraindications to transplant procedure

Primary outcomes:
measure: 6-month Acute Cellular-mediated Rejection Rate (CMR)
timeFrame: Up to 6 months
measure: 6-month Acute Antibody-mediated Rejection Rate (AMR)
timeFrame: Up to 6 months
measure: 6-month Cumulative Rejection Incidence (Either CMR, AMR or Both)
timeFrame: Up to 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: The Johns Hopkins University, School of Medicine
state: Maryland
Study officials:
affiliation: Johns Hopkins University , SOM
name: Robert A Montgomery, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University, SOM
name: Christopher E Simpkins, M.D.
role: STUDY_DIRECTOR
References:
citation: Haas M, Sis B, Racusen LC, Solez K, Glotz D, Colvin RB, Castro MC, David DS, David-Neto E, Bagnasco SM, Cendales LC, Cornell LD, Demetris AJ, Drachenberg CB, Farver CF, Farris AB 3rd, Gibson IW, Kraus E, Liapis H, Loupy A, Nickeleit V, Randhawa P, Rodriguez ER, Rush D, Smith RN, Tan CD, Wallace WD, Mengel M; Banff meeting report writing committee. Banff 2013 meeting report: inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant. 2014 Feb;14(2):272-83. doi: 10.1111/ajt.12590.
citation: Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M, Halloran PF, Baldwin W, Banfi G, Collins AB, Cosio F, David DS, Drachenberg C, Einecke G, Fogo AB, Gibson IW, Glotz D, Iskandar SS, Kraus E, Lerut E, Mannon RB, Mihatsch M, Nankivell BJ, Nickeleit V, Papadimitriou JC, Randhawa P, Regele H, Renaudin K, Roberts I, Seron D, Smith RN, Valente M. Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant. 2008 Apr;8(4):753-60. doi: 10.1111/j.1600-6143.2008.02159.x. Epub 2008 Feb 19.