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Open Access Study protocol

Rationale and design of the RIACT–study: a multi-center placebo controlled double blind study to test the efficacy of RItuximab in Acute Cellular tubulointerstitial rejection with B-cell infiltrates in renal Transplant patients: study protocol for a randomized controlled trial

Lena Schiffer1*, Mario Schiffer1, Saskia Merkel1, Anke Schwarz1, Michael Mengel3, Christopher Jürgens4, Christoph Schroeder5, Alexander A Zoerner5, Kerstin Püllmann6, Verena Bröcker7, Jan U Becker7, Maximilian E Dämmrich7, Jana Träder7, Anika Großhennig2, Frank Biertz2, Hermann Haller1, Armin Koch2 and Wilfried Gwinner1

Author Affiliations

1 Department of Medicine/Nephrology, Hannover Medical School, Carl Neuberg Str. 1, Hannover, 30625, Germany

2 Department of Biostatistics, Hannover Medical School, Carl Neuberg Str. 1, Hannover, 30625, Germany

3 Alberta Transplant Applied Genomics Centre, University of Alberta, Alberta, Canada

4 Department of Pharmacy, Hannover Medical School, Carl Neuberg Str. 1, Hannover, 30625, Germany

5 Institute for Clinical Pharmacology, Hannover Medical School, Carl Neuberg Str. 1, Hannover, 30625, Germany

6 Department of Hematology and Oncology, Hannover Medical School, Carl Neuberg Str. 1, Hannover, 30625, Germany

7 Department of Pathology, Hannover Medical School, Carl Neuberg Str. 1, Hannover, 30625, Germany

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Trials 2012, 13:199  doi:10.1186/1745-6215-13-199

Published: 26 October 2012

Abstract

Background

Acute kidney allograft rejection is a major cause for declining graft function and has a negative impact on the long-term graft survival. The majority (90%) of acute rejections are T-cell mediated and, therefore, the anti-rejection therapy targets T-cell-mediated mechanisms of the rejection process. However, there is increasing evidence that intragraft B-cells are also important in the T-cell-mediated rejections. First, a significant proportion of patients with acute T-cell-mediated rejection have B-cells present in the infiltrates. Second, the outcome of these patients is inferior, which has been related to an inferior response to the conventional anti-rejection therapy. Third, treatment of these patients with an anti-CD20 antibody (rituximab) improves the allograft outcome as reported in single case observations and in one small study. Despite the promise of these observations, solid evidence is required before incorporating this treatment option into a general treatment recommendation.

Methods/Design

The RIACT study is designed as a randomized, double-blind, placebo-controlled, parallel group multicenter Phase III study. The study examines whether rituximab, in addition to the standard treatment with steroid-boli, leads to an improved one-year kidney allograft function, compared to the standard treatment alone in patients with acute T-cell mediated tubulointerstitial rejection and significant B-cell infiltrates in their biopsies. A total of 180 patients will be recruited.

Discussion

It is important to clarify the relevance of anti-B cell targeting in T-cell mediated rejection and answer the question whether this novel concept should be incorporated in the conventional anti-rejection therapy.

Trial registration

Clinical trials gov. number: NCT01117662

Keywords:
Cellular kidney allograft rejection; B-cells; Rituximab