Phase IV Study to Evaluate Calcineurin Inhibitor Reduced, Steroid Free Immunosuppression After Renal Transplantation

NCT00724022 | Completed Phase 4

• 3 other identifiers: IT1850071EudraCT No. 2007-006516-31DRKS00000452
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 25

Brief Summary

Current practice of immune suppressive standard therapy after renal transplantation in non-risk patients is a triple therapy consisting of steroids, a calcineurin inhibitor and MMF. The aim of this clinical trial is to combine a reduction of CNI using tacrolimus and a concept of not using steroids in order to establish an immunosuppressive regimen in immunologically non-risk patients that is efficient and causes as few side effects as possible.

Conditions

Disorder Related to Renal Transplantation

Keywords

Kidney transplant status; Steroid free; Reduced; Calcineurin; Inhibitor; Immunosuppression

Outcome Measures

Primary Outcomes (1)

• Efficacy of immunosuppression measured in rejection rate confirmed by biopsy according to BANFF 97, modified 2005.

  one year after transplantation

Secondary Outcomes (20)

• Rate of patients with steroid-free immunosuppression

• patient and graft survival rate

• graft function (calculated by the Cock- croft-Gault and MDRD-IV formula respectively calculated creatinine clearance by the Nankivell formula respectively cystatin C measurement)

• Number of steroid-resistant rejections

• blood pressure level and also amount and types of blood pressure medications

Study Arms (3)

A

OTHER

Standard: Advagraf, CellCept, Decortin H + 2x Simulect Day 0 + 4

Drug: Basiliximab, Tacrolimus, MMF, Prednisolon

B

EXPERIMENTAL

Steroidfree: Advagraf, Cellcept, Decortin H until Day 8, 2x Simulect Day 0 + 4

Drug: Basiliximab, Tacrolimus, MMF

C

EXPERIMENTAL

Steroidfree: Advagraf, Cellcept, Decortin H until Day 8, 3 x Thymoglobulin

Drug: Tacrolimus, MMF, rATG

Interventions

Basiliximab, Tacrolimus, MMF, Prednisolon DRUG

Control group. Therapy with Prednisolon.

Also known as: Simulect, Advagraf, CellCept, Decortin

A

Basiliximab, Tacrolimus, MMF DRUG

No Prednisolon after 7 days

Also known as: Simulect, Advagraf, CellCept

B

Tacrolimus, MMF, rATG DRUG

Induction therapy: rATG instead of Basiliximab. No Prednisolon.

Also known as: Advagraf, CellCept, Thymoglobulin

C

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Post mortal kidney donation or living donation
• Primary and secondary renal transplantation, unless the graft was lost due to severe rejection within the first year
• PRA level ≤ 20%.
• Recipient ≥ 18 to 75 years of age
• AB0-compatible
• Negative crosshatch
• Patients with a signed informed consent form
• Women of child-bearing age must agree to an efficient contraception

You may not qualify if:

• Third or multiple transplantation
• Transplantation per a "non-heart beating" donor
• HLA-identical living donation
• Incompatibility to study medication (allergy, intolerance, hypersensitivity)
• Patients with existing malignant underlying disease or tumour anamnesis \< 5 years. Exception: basaloma or squamous cell carcinoma of the skin after successful therapy
• Female patients who do not use a safe method of contraception
• Patients with clinically significant, uncontrolled infectious diseases (incl. HIV) and/or severe diarrhoea, emesis, active malabsorption of the upper gastrointestinal tract or active peptic ulcer
• Patients currently, resp. within the last 30 days, participating in other studies
• Primary focal-sclerosing glomerulonephritis and membranoproliferative glomerulonephritis as an underlying disease
• Autoimmune disease as underlying disease (collagen diseases, colitis, HUS, SLE) which might require chronic cortisone therapy
• Additional disease requiring temporary or chronic cortisone therapy (including inhalation medicine)
• Chronic hepatitis B and hepatitis C infection
• Thrombopenia \< 70.000/mm3 or leukopenia \< 2.500/mm3 or neutropenia \< 1500/ mm3.
• Patients with hepatocirrhosis Child B or C or another severe disease of the liver
• Patients with symptoms of a significant somatic or psychiatric / mental illness. Patients who are not able to realize nature, relevance and consequences of the clinical trial and who are not able to comply, to cooperate and communicate adequately and to follow the instructions of the study or even to give their informed consent (according to § 40 article 4 and § 41 article 2 and 3 AMG).

Sponsors & Collaborators

• University Hospital Freiburg: lead
• Roche Pharma AG: collaborator
• Astellas Pharma GmbH: collaborator
• Genzyme, a Sanofi Company: collaborator

Study Sites (25)

Universitaetsklinikum Berlin

Berlin, 13353, Germany

Location

Universitaetsklinikum Bonn

Bonn, 53105, Germany

Location

Klinikum Bremen-Mitte

Bremen, 28177, Germany

Location

Universitaetsklinikum Koeln

Cologne, 50924, Germany

Location

Kliniken der Stadt Köln gGmbH - Krankenhaus Köln-Merheim

Cologne, 51109, Germany

Location

Carl Gustav Carus Universitätsklinikum

Dresden, 01307, Germany

Location

Universitaetsklinikum Erlangen

Erlangen, 91054, Germany

Location

Universitaetsklinikum Essen

Essen, 45122, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt am Main, 60590, Germany

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Nephrologisches Zentrum Niedersachsen

Hannoversch Münden, 34346, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Universitätsklinikum Jena

Jena, 07747, Germany

Location

Transplantationszentrum Kaiserslautern

Kaiserslautern, 67655, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

Universitätsklinikum Schleswig-Holstein Campus Lübeck

Lübeck, 23538, Germany

Location

Universitätsklinikum Mainz

Mainz, 55131, Germany

Location

Universitaetsklinikum Mannheim

Mannheim, 68167, Germany

Location

Universitätsklinikum München LMU

München, 81377, Germany

Location

Klinikum rechts der Isar der TU München

München, 81675, Germany

Location

Universitaetsklinikum der WWU Münster

Münster, 48149, Germany

Location

Universitätsklinikum Regensburg

Regensburg, 93053, Germany

Location

Universitätsklinikum Rostock

Rostock, 18057, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

Universitaetsklinikum Würzburg

Würzburg, 97080, Germany

Location

Related Publications (4)

• Wajih Z, Karpe KM, Walters GD. Interventions for BK virus infection in kidney transplant recipients. Cochrane Database Syst Rev. 2024 Oct 9;10(10):CD013344. doi: 10.1002/14651858.CD013344.pub2.

  PMID: 39382091 DERIVED

• Stumpf J, Thomusch O, Opgenoorth M, Wiesener M, Pascher A, Woitas RP, Suwelack B, Rentsch M, Witzke O, Rath T, Banas B, Benck U, Sommerer C, Kurschat C, Lopau K, Weinmann-Menke J, Jaenigen B, Trips E, Hugo C. Excellent efficacy and beneficial safety during observational 5-year follow-up of rapid steroid withdrawal after renal transplantation (Harmony FU study). Nephrol Dial Transplant. 2023 Dec 20;39(1):141-150. doi: 10.1093/ndt/gfad130.

  PMID: 37391381 DERIVED

• Wittenbrink N, Herrmann S, Blazquez-Navarro A, Bauer C, Lindberg E, Wolk K, Sabat R, Reinke P, Sawitzki B, Thomusch O, Hugo C, Babel N, Seitz H, Or-Guil M. A novel approach reveals that HLA class 1 single antigen bead-signatures provide a means of high-accuracy pre-transplant risk assessment of acute cellular rejection in renal transplantation. BMC Immunol. 2019 Apr 27;20(1):11. doi: 10.1186/s12865-019-0291-2.

  PMID: 31029086 DERIVED

• Thomusch O, Wiesener M, Opgenoorth M, Pascher A, Woitas RP, Witzke O, Jaenigen B, Rentsch M, Wolters H, Rath T, Cingoz T, Benck U, Banas B, Hugo C. Rabbit-ATG or basiliximab induction for rapid steroid withdrawal after renal transplantation (Harmony): an open-label, multicentre, randomised controlled trial. Lancet. 2016 Dec 17;388(10063):3006-3016. doi: 10.1016/S0140-6736(16)32187-0. Epub 2016 Nov 19.

  PMID: 27871759 DERIVED

MeSH Terms

Interventions

Basiliximab; Tacrolimus; Mycophenolic Acid; Prednisone; thymoglobulin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Ulrich Hopt, Prof.Dr.Dr.

  University Hospital Freiburg

  STUDY DIRECTOR

• Oliver Thomusch, Prof. Dr.

  University Hospital Freiburg

  PRINCIPAL INVESTIGATOR

• Christian Hugo, Prof. Dr.

  Universitaetsklinikum Erlangen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 25, 2008
• First Posted: July 29, 2008
• Study Start: June 1, 2008
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: October 1, 2014

Record last verified: 2014-09

Locations

DE (25)