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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
56
Following each plasmapheresis session, 100 mg/kg of Cytogam (CMVIg) (Cytogam, CSL Behring, King of Prussia, PA) was administered
The Johns Hopkins University, School of Medicine
Baltimore, Maryland, United States
6-month Acute Cellular-mediated Rejection Rate (CMR)
Per 2007 international Banff Classification Criteria, CMR 1A was diagnosed on biopsies displaying significant interstitial infiltration (\>25% of parenchyma affected, i2 or i3) and foci of moderate tubulitis (t2). CMR IB was diagnosed in cases with significant interstitial infiltration (\>25% of parenchyma affected, i2 or i3) and foci of severe tubulitis (t3). CMR IIA were cases with mild-to-moderate intimal arteritis (v1), while CMR IIB were those with severe intimal arteritis comprising \>25% of the luminal area (v2). CMR III were those cases with transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation (v3).
Time frame: Up to 6 months
6-month Acute Antibody-mediated Rejection Rate (AMR)
A diagnosis of AMR was based on the 2013 international Banff Classification Criteria and is defined as the presence of circulating donor-specific antibody (DSA) and either: 1) peritubular capillary staining of C4d and at least one of the following: peritubular capillaritis (ptc) score\>0, glomerulitis (g) score\>0, acute thrombotic microangiopathy (TMA) in the absence of any other cause, or other features consistent with AMR (endothelial injury, fibrin thrombi, microinfarctions, interstitial hemorrhage), or 2) absence of capillary staining of C4d and the presence of ptc\>0 and g\>0 or ptc\>0 or g\>0 and acute TMA, in the absence of any other cause of TMA.
Time frame: Up to 6 months
6-month Cumulative Rejection Incidence (Either CMR, AMR or Both)
Biopsy shows evidence of either AMR or CMR or evidence both.
Time frame: Up to 6 months
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2 gm/day. Standard of care
To achieve serum level of 8-10 ng/ml.
100 mg intra-operatively, and 25 mg every 6h post-operatively for six doses
Taper over three months to 5 mg daily
Following each plasmapheresis session, 100 mg/kg of Cytogam (CMVIg) (Cytogam, CSL Behring, King of Prussia, PA) was administered