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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by Hannover Medical School
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 30, 2012
Last verified: October 2012
  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 Cellular 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: 118
Study Start Date: May 2012
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: May 2016 (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
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. Kidney transplantation > 6 weeks and < 12 months
  3. Proof of an acute cellular tubulointerstitial rejection in kidney transplant according to Banff-criteria (grade IA/B) or Banff Borderline Rejection with simultaneous increase of creatinine (≥ 20% over baseline creatinine) and an infiltrate with CD 20+ lymphocytes (>30 /field of view), that are detected in the course of a protocol biopsy or an indication biopsy.
  4. C4d- and SV40-negativity in the biopsy
  5. Creatinine clearance after 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.
  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01117662

Contacts
Contact: Hermann Haller, Professor, MD +49(0)511 532 ext 6319 nephrologie@mh-hannover.de

Locations
Germany
Hannover Medical School Recruiting
Hannover, Lower Saxony, Germany, 30625
Principal Investigator: Hermann Haller, Prof., MD         
Universitätsklinikum der RWTH Aachen Medizinische Klinik II Recruiting
Aachen, Germany, 52074
Universitätsklinikum Erlangen Nephrologie und Hypertensiologie Not yet recruiting
Erlangen, Germany, 91054
Universitätsklinikum Essen Klinik für Nephrologie Recruiting
Essen, Germany, 45147
Universitätsklinikum Freiburg Medzinische Klinik IV Nephrologie Freiburg Recruiting
Freiburg, Germany, 79106
Nephrologisches Zentrum Niedersachsen 34346 Hannoversch Münden Recruiting
Hannoversch Münden, Germany, 34346
Universitätsklinikum Jena Klinik für Innere Medizin III Recruiting
Jena, Germany, 07747
Universitätsklinikum Schleswig-Holstein Campus Kiel Klinik für Nieren- und Hochdruckkrankheiten Kiel Recruiting
Kiel, Germany, 24105
Universitätsklinikum Köln Medizinische Klinik IV Nephrologie Not yet recruiting
Köln, Germany, 50937
Kliniken der Stadt Köln gGmbH Medizinische Klinik I Recruiting
Köln, Germany, 51109
Medizinische Klinik und Poliklinik I der Ludwig-Maximilians-Uniklinik München Klinikum Großhadern Not yet recruiting
München, Germany, 81377
Universitätsklinikum Münster Innere Medizin / Nephrologie Recruiting
Münster, Germany, 48149
Sponsors and Collaborators
Hannover Medical School
German Federal Ministry of Education and Research
  More Information

No publications provided by Hannover Medical School

Additional 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 30, 2012
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Hannover Medical School:
transplantation
acute rejection
kidney

Additional relevant MeSH terms:
Rituximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on October 19, 2014