title: 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.
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
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Clinical trials gov. number: NCT01117662.
authors.affiliation: Department of Medicine/Nephrology, Hannover Medical School, Carl Neuberg Str, 1, Hannover, 30625, Germany. schiffer.lena@mh-hannover.de
authors.forename: Lena
authors.initials: L
authors.lastname: Schiffer
authors.forename: Mario
authors.initials: M
authors.lastname: Schiffer
authors.forename: Saskia
authors.initials: S
authors.lastname: Merkel
authors.forename: Anke
authors.initials: A
authors.lastname: Schwarz
authors.forename: Michael
authors.initials: M
authors.lastname: Mengel
authors.forename: Christopher
authors.initials: C
authors.lastname: Jürgens
authors.forename: Christoph
authors.initials: C
authors.lastname: Schroeder
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Zoerner
authors.forename: Kerstin
authors.initials: K
authors.lastname: Püllmann
authors.forename: Verena
authors.initials: V
authors.lastname: Bröcker
authors.forename: Jan U
authors.initials: JU
authors.lastname: Becker
authors.forename: Maximilian E
authors.initials: ME
authors.lastname: Dämmrich
authors.forename: Jana
authors.initials: J
authors.lastname: Träder
authors.forename: Anika
authors.initials: A
authors.lastname: Grosshennig
authors.forename: Frank
authors.initials: F
authors.lastname: Biertz
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.forename: Armin
authors.initials: A
authors.lastname: Koch
authors.forename: Wilfried
authors.initials: W
authors.lastname: Gwinner
mesh_terms: D000208:Acute Disease; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000473:pathology*; D002985:Clinical Protocols; D004311:Double-Blind Method; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects*; D012107:Research Design; D000069283:Rituximab; D018401:Sample Size
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab