Efficacy of Rituximab in Acute Cellular Rejection in Renal Transplant Patients (RIACT)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
German Federal Ministry of Education and Research
Information provided by (Responsible Party):
Hannover Medical School
ClinicalTrials.gov Identifier:
NCT01117662
First received: April 28, 2010
Last updated: October 1, 2015
Last verified: October 2015
  Purpose

Acute kidney allograft rejection is the major cause for a loss of graft function and has a negative impact on long-term graft survival. Anti-rejection therapy traditionally focuses on T cell-mediated mechanisms of renal allograft rejection. However, available agents that affect T-cell pathways have only little impact on long-term graft survival. There is increasing evidence that B-cells play an important role in acute transplant rejections. CD20+ B cell infiltrates in acute T-cell mediated rejections are frequent and correlate with a worse response to conventional anti-rejection treatment and an increased risk of graft loss. In one pilot study, supported by several case reports, a beneficial effect of Rituximab for the treatment of acute rejection episodes with intrarenal B-cell infiltrates was shown. However, despite the promise of these observations solid evidence is required before incorporating this treatment option into a general treatment recommendation.

In a multicenter randomized placebo controlled double blind phase III trial the investigators want to demonstrate that Rituximab in addition to standard treatment with steroid-boli is superior to the standard treatment alone regarding long-term kidney function. If the proposed study proves that Rituximab treatment of acute rejections is beneficial for the long-term allograft function, the conventional rejection therapy needs to be revised to this novel concept of B- cell targeting


Condition Intervention Phase
Acute Rejection
Drug: Rituximab
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Efficacy of Rituximab in Acute Cellular Rejection With B-cell Infiltrates in Renal Transplant Patients - Randomized Placebo Controlled Double Blind Trial

Resource links provided by NLM:


Further study details as provided by Hannover Medical School:

Primary Outcome Measures:
  • Change of the GFR (glomerular filtration rate) one year after intervention compared to the baseline GFR before the rejection, which is calculated by a defined algorithm [ Time Frame: Baseline, 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression of interstitial fibrosis and tubular atrophy between the biopsy that led to enrolment in the study and a scheduled protocol biopsy one year after intervention ("∆IFTA-Score") [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 180
Study Start Date: May 2012
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rituximab
Intravenous application of Rituximab 375mg/m² body surface in 250 ml NaCl 0,9 % over 4 hours
Drug: Rituximab
Intravenous application of Rituximab 375mg/m² body surface in 250 ml NaCl 0,9 % over 4 hours
Other Name: MabThera
Placebo Comparator: Control
Intravenous application of placebo (NaCl 0,9 %) matching active treatment
Drug: Placebo
Intravenous application of placebo (NaCl 0,9 %) matching active treatment

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. male or female patients age ≥ 18 at the time of the inclusion in the study
  2. male or female patients after kidney transplantation if medically justifiable (cave: previous immunosuppression, particularly prior induction therapies or biologicals).
  3. Proof of an acute rejection in kidney transplant according to Banff-criteria: T-cell-mediated rejection as borderline, grade IA/B, IIA/B (no v-only), if one or more results are available as significant B-cell infiltrates CD20≥20 / high power field, glomerulitis, peritubular capillaritis or C4d positivity (with the exception of ABO-incompatible transplantations) as well as patients who have no T-cell-mediated acute rejection, but signs of acute humoral rejection (as listed above according to the criteria glomerulitis, peritubular capillaritis, C4d positivity) who have to be treated according to medical opinion of the physician with steroid therapy. The evidence of rejection can be performed by a protocol or indication biopsy.
  4. SV40-negativity in the biopsy
  5. GFR calculated using the MDRD-Formula > 25 ml/min/1,73 m² in the time period before the noticed rejection.
  6. Presence of a negative pregnancy test and consent to a highly effective contraceptive method (i.e. failure rate less than 1% per year, which are implants, injectable contraceptives, combined oral contraceptives, intrauterine devices (only hormone spirals), sexual abstinence or vasectomy of the partner) in patients of child-bearing age. This is not required when bilateral sterilization or ovariectomy of the patient and in patients that have exclusively female sex partners. Presence of consent to a highly effective contraceptive method for male patient.
  7. Informed consent

Exclusion criteria:

  1. Known contraindications, resp. incompatibility for Rituximab and/or for the concomitant medication
  2. Administration of Rituximab within the last 12 months before inclusion
  3. Simultaneous participation in an other clinical study or participation in an other clinical study within the last 30 days
  4. Breastfeeding women or pregnant women
  5. Persons who fail to assess essence, meaning and significance of the clinical study and act along these lines (according to § 40 Abs. 4 and § 41 Abs. 2 and Abs. 3 AMG)
  6. Existence of an active CMV-infection, existence of a HIV-infection, existence of a replicative hepatitis B or C, existence of other grave infections
  7. Cardiac insufficiency in phase NYHA III-IV
  8. High grade cardiac arrhythmias
  9. Unstable coronary heart disease
  10. Poorly adjusted diabetes mellitus (HbA1c > 10 %) at the time of the inclusion in the study.
  11. State after splenectomy
  12. Contra-indication referring to a renewed transplant biopsy (e.g. coagulopathy, anticoagulation)
  13. Other exclusion criteria according to the estimate of the attending doctor (e.g. aggravation of the general health condition, occurrence of a malignant disease)
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01117662

Locations
Germany
Hannover Medical School
Hannover, Lower Saxony, Germany, 30625
Universitätsklinikum der RWTH Aachen Medizinische Klinik II
Aachen, Germany, 52074
Charité Campus Mitte Universitätsmedizin Berlin
Berlin, Germany, 10117
Universitätsklinikum Düsseldorf Klinik für Nephrologie
Düsseldorf, Germany, 40225
Universitätsklinikum Erlangen Nephrologie und Hypertensiologie
Erlangen, Germany, 91054
Universitätsklinikum Essen Klinik für Nephrologie
Essen, Germany, 45147
Universitätsklinikum Freiburg Medzinische Klinik IV Nephrologie Freiburg
Freiburg, Germany, 79106
Nephrologisches Zentrum Niedersachsen 34346 Hannoversch Münden
Hannoversch Münden, Germany, 34346
Universitätsklinikum Jena Klinik für Innere Medizin III
Jena, Germany, 07747
Universitätsklinikum Schleswig-Holstein Campus Kiel Klinik für Nieren- und Hochdruckkrankheiten Kiel
Kiel, Germany, 24105
Universitätsklinikum Köln Medizinische Klinik IV Nephrologie
Köln, Germany, 50937
Kliniken der Stadt Köln gGmbH Medizinische Klinik I
Köln, Germany, 51109
Medizinische Klinik und Poliklinik I der Ludwig-Maximilians-Uniklinik München Klinikum Großhadern
München, Germany, 81377
Universitätsklinikum Münster Innere Medizin / Nephrologie
Münster, Germany, 48149
Sponsors and Collaborators
Hannover Medical School
German Federal Ministry of Education and Research
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hannover Medical School
ClinicalTrials.gov Identifier: NCT01117662     History of Changes
Other Study ID Numbers: 200710602 
Study First Received: April 28, 2010
Last Updated: October 1, 2015
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Hannover Medical School:
transplantation
acute rejection
kidney

Additional relevant MeSH terms:
Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 21, 2016