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

NCT ID: NCT00275509

Last Updated: 2018-01-18

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

56 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-01-31

Study Completion Date

2010-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Kidney Failure, Chronic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Thymoglobulin

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

Group Type EXPERIMENTAL

Thymoglobulin

Intervention Type DRUG

Plasmapheresis

Intervention Type OTHER

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

Mycophenolate mofetil

Intervention Type DRUG

2 gm/day. Standard of care

Tacrolimus

Intervention Type DRUG

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

Dexamethasone

Intervention Type DRUG

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

Prednisone

Intervention Type DRUG

Taper over three months to 5 mg daily

Cytogam

Intervention Type DRUG

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

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).

Group Type EXPERIMENTAL

Daclizumab

Intervention Type DRUG

Plasmapheresis

Intervention Type OTHER

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

Mycophenolate mofetil

Intervention Type DRUG

2 gm/day. Standard of care

Tacrolimus

Intervention Type DRUG

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

Dexamethasone

Intervention Type DRUG

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

Prednisone

Intervention Type DRUG

Taper over three months to 5 mg daily

Cytogam

Intervention Type DRUG

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

Interventions

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Thymoglobulin

Intervention Type DRUG

Daclizumab

Intervention Type DRUG

Plasmapheresis

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

Intervention Type OTHER

Mycophenolate mofetil

2 gm/day. Standard of care

Intervention Type DRUG

Tacrolimus

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

Intervention Type DRUG

Dexamethasone

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

Intervention Type DRUG

Prednisone

Taper over three months to 5 mg daily

Intervention Type DRUG

Cytogam

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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Johns Hopkins University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Robert A Montgomery, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University , SOM

Christopher E Simpkins, M.D.

Role: STUDY_DIRECTOR

Johns Hopkins University, SOM

Locations

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The Johns Hopkins University, School of Medicine

Baltimore, Maryland, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 24472190 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18294345 (View on PubMed)

Other Identifiers

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IRB00078055

Identifier Type: -

Identifier Source: org_study_id

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