Induction Therapy Study in Live Donor Kidney Transplant Recipients With a Positive Crossmatch

Johns Hopkins University

Status and phase: Completed; Phase 3

Conditions: Kidney Failure, Chronic

Treatments: Drug: Daclizumab; Drug: Cytogam; Drug: Tacrolimus; Drug: Prednisone; Drug: Dexamethasone; Drug: Thymoglobulin; Drug: Mycophenolate mofetil; Other: Plasmapheresis

Study type: Interventional

Funder types: Other

Identifiers

NCT00275509

IRB00078055

Details and patient eligibility

About

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.

Full 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.

Enrollment: 56 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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56 participants in 2 patient groups

Thymoglobulin

Experimental group

Description:

Thymoglobulin was administered as 1.5 mg/kg prior to reperfusion followed by 6 post-operative doses on days 1 through 6.

Treatment:

Drug: Prednisone

Drug: Dexamethasone

Drug: Tacrolimus

Drug: Mycophenolate mofetil

Other: Plasmapheresis

Drug: Thymoglobulin

Drug: Cytogam

Daclizumab

Experimental group

Description:

Daclizumab was administered as 2 mg/kg prior to reperfusion followed by 1 mg/kg every other week for 8 weeks post-operatively (4 post-operative doses).

Treatment:

Drug: Prednisone

Drug: Dexamethasone

Drug: Tacrolimus

Drug: Daclizumab

Drug: Mycophenolate mofetil

Other: Plasmapheresis

Drug: Cytogam