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

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ClinicalTrials.gov Identifier: NCT00275509
Recruitment Status : Completed
First Posted : January 12, 2006
Results First Posted : December 20, 2017
Last Update Posted : January 18, 2018
Sponsor:
Information provided by (Responsible Party):
Johns Hopkins University

January 10, 2006
January 12, 2006
November 20, 2017
December 20, 2017
January 18, 2018
January 2007
June 2010   (Final data collection date for primary outcome measure)
  • 6-month Acute Cellular-mediated Rejection Rate (CMR) [ Time Frame: Up to 6 months ]
    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).
  • 6-month Acute Antibody-mediated Rejection Rate (AMR) [ Time Frame: Up to 6 months ]
    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.
  • 6-month Cumulative Rejection Incidence (Either CMR, AMR or Both) [ Time Frame: Up to 6 months ]
    Biopsy shows evidence of either AMR or CMR or evidence both.
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Complete list of historical versions of study NCT00275509 on ClinicalTrials.gov Archive Site
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Induction Therapy Study in Live Donor Kidney Transplant Recipients With a Positive Crossmatch
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
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.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Kidney Failure, Chronic
  • Drug: Thymoglobulin
  • Drug: Daclizumab
  • Other: Plasmapheresis
    Following each plasmapheresis session, 100 mg/kg of Cytogam (CMVIg) (Cytogam, CSL Behring, King of Prussia, PA) was administered
  • Drug: Mycophenolate mofetil
    2 gm/day. Standard of care
  • Drug: Tacrolimus
    To achieve serum level of 8-10 ng/ml.
  • Drug: Dexamethasone
    100 mg intra-operatively, and 25 mg every 6h post-operatively for six doses
  • Drug: Prednisone
    Taper over three months to 5 mg daily
  • Drug: Cytogam
    Following each plasmapheresis session, 100 mg/kg of Cytogam (CMVIg) (Cytogam, CSL Behring, King of Prussia, PA) was administered
  • Experimental: Thymoglobulin
    Thymoglobulin was administered as 1.5 mg/kg prior to reperfusion followed by 6 post-operative doses on days 1 through 6.
    Interventions:
    • Drug: Thymoglobulin
    • Other: Plasmapheresis
    • Drug: Mycophenolate mofetil
    • Drug: Tacrolimus
    • Drug: Dexamethasone
    • Drug: Prednisone
    • Drug: Cytogam
  • Experimental: Daclizumab
    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).
    Interventions:
    • Drug: Daclizumab
    • Other: Plasmapheresis
    • Drug: Mycophenolate mofetil
    • Drug: Tacrolimus
    • Drug: Dexamethasone
    • Drug: Prednisone
    • Drug: Cytogam

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
56
110
June 2010
June 2010   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00275509
IRB00078055
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Johns Hopkins University
Johns Hopkins University
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Principal Investigator: Robert A Montgomery, M.D., Ph.D. Johns Hopkins University , SOM
Study Director: Christopher E Simpkins, M.D. Johns Hopkins University, SOM
Johns Hopkins University
December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP