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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

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.

Condition or disease Intervention/treatment Phase
Kidney Failure, Chronic Drug: Thymoglobulin Drug: Daclizumab Other: Plasmapheresis Drug: Mycophenolate mofetil Drug: Tacrolimus Drug: Dexamethasone Drug: Prednisone Drug: Cytogam Phase 3

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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
Actual Study Start Date : January 2007
Actual Primary Completion Date : June 2010
Actual Study Completion Date : June 2010

Resource links provided by the National Library of Medicine

Drug Information available for: Daclizumab

Arm Intervention/treatment
Experimental: Thymoglobulin
Thymoglobulin was administered as 1.5 mg/kg prior to reperfusion followed by 6 post-operative doses on days 1 through 6.
Drug: Thymoglobulin
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: 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).
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




Primary Outcome Measures :
  1. 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).

  2. 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.

  3. 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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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00275509


Locations
United States, Maryland
The Johns Hopkins University, School of Medicine
Baltimore, Maryland, United States, 21205
Sponsors and Collaborators
Johns Hopkins University
Investigators
Principal Investigator: Robert A Montgomery, M.D., Ph.D. Johns Hopkins University , SOM
Study Director: Christopher E Simpkins, M.D. Johns Hopkins University, SOM

Publications:
Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00275509     History of Changes
Other Study ID Numbers: IRB00078055
First Posted: January 12, 2006    Key Record Dates
Results First Posted: December 20, 2017
Last Update Posted: January 18, 2018
Last Verified: December 2017

Keywords provided by Johns Hopkins University:
kidney
transplantation
positive crossmatch
antibody mediated rejection
rejection
induction
therapy
trial

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Failure, Chronic
Kidney Diseases
Urologic Diseases
Renal Insufficiency, Chronic
Dexamethasone
Prednisone
Mycophenolic Acid
Tacrolimus
Thymoglobulin
Antilymphocyte Serum
Daclizumab
Immunoglobulin G
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic