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

NCT00275509 | Completed Phase 3 Results

• 1 other identifier: IRB00078055
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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.

Conditions

Kidney Failure, Chronic

Keywords

kidney; transplantation; positive crossmatch; antibody mediated rejection; rejection; induction; therapy; trial

Outcome Measures

Primary Outcomes (3)

• 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).

  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.

  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.

  Up to 6 months

Study Arms (2)

Thymoglobulin

EXPERIMENTAL

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; Drug: Mycophenolate mofetil; Drug: Tacrolimus; Drug: Dexamethasone; Drug: Prednisone; Drug: Cytogam

Daclizumab

EXPERIMENTAL

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; Drug: Mycophenolate mofetil; Drug: Tacrolimus; Drug: Dexamethasone; Drug: Prednisone; Drug: Cytogam

Interventions

Thymoglobulin DRUG

Thymoglobulin

Daclizumab DRUG

Daclizumab

Plasmapheresis OTHER

Following each plasmapheresis session, 100 mg/kg of Cytogam (CMVIg) (Cytogam, CSL Behring, King of Prussia, PA) was administered

Daclizumab; Thymoglobulin

Mycophenolate mofetil DRUG

2 gm/day. Standard of care

Daclizumab; Thymoglobulin

Tacrolimus DRUG

To achieve serum level of 8-10 ng/ml.

Daclizumab; Thymoglobulin

Dexamethasone DRUG

100 mg intra-operatively, and 25 mg every 6h post-operatively for six doses

Daclizumab; Thymoglobulin

Prednisone DRUG

Taper over three months to 5 mg daily

Daclizumab; Thymoglobulin

Cytogam DRUG

Following each plasmapheresis session, 100 mg/kg of Cytogam (CMVIg) (Cytogam, CSL Behring, King of Prussia, PA) was administered

Daclizumab; Thymoglobulin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

The Johns Hopkins University, School of Medicine

Baltimore, Maryland, 21205, United States

Location

Related Publications (2)

• 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.

  PMID: 24472190 BACKGROUND

• 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.

  PMID: 18294345 BACKGROUND

MeSH Terms

Conditions

Kidney Failure, Chronic; Rejection, Psychology

Interventions

thymoglobulin; Daclizumab; Plasmapheresis; Mycophenolic Acid; Tacrolimus; Dexamethasone; Prednisone; cytomegalovirus-specific hyperimmune globulin

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Blood Component Removal; Therapeutics; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Macrolides; Lactones; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Pregnadienediols

Results Point of Contact

• Title: Robert Montgomery, MD
• Organization: New York University Langone Transplant Institute

Robert.Montgomery@nyumc.org

646-501-2418

Study Officials

• Robert A Montgomery, M.D., Ph.D.

  Johns Hopkins University , SOM

  PRINCIPAL INVESTIGATOR

• Christopher E Simpkins, M.D.

  Johns Hopkins University, SOM

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2006
• First Posted: January 12, 2006
• Study Start: January 1, 2007
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: January 18, 2018
• Results First Posted: December 20, 2017

Record last verified: 2017-12

Locations

US (1)