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

NCT ID: NCT00724022

Last Updated: 2014-10-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 600 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2014-07-31

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.

Detailed Description

In this triple arm, prospectively randomized multi centre phase IV study 200 patients per study arm will be investigated for 12 months.

Based on the results of the Symphony study the low dose tacrolimus study arm will be modified to further improve efficacy (prevention of BPAR, best possible renal function) and safety (adverse event profile regarding infections, cardiovascular risk factors, malignant tumours) of immunosuppression. For this, CNI will be reduced and in addition the rate of steroid free patients after 1 week will be maximized to achieve a long lasting improved post surgical cardiovascular risk profile (in particular concerning de novo induction of diabetes mellitus and other adverse events caused by steroids). Safety should be increased without loss of efficacy of immunosuppression (measured in rejection rate and allograft loss rate) as compared to an immune suppressive therapy comprising steroids. Therefore, following the successful study arm of the Symphony study, immunosuppression in the first of the three study arms comprises a steroid in combination with Advagraf and CellCept in addition to a two dose induction therapy with Simulect (group A). The regimen of the second study arm is similar but discontinues steroids on day seven after transplantation (group B). Therapy of group three is similar to group B but Simulect is replaced by T-cell depleting polyclonal antibodies (Thymoglobulin) (group C).

Conditions

Disorder Related to Renal Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

A

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

Group Type: OTHER

Basiliximab, Tacrolimus, MMF, Prednisolon

Intervention Type: DRUG

Control group. Therapy with Prednisolon.

B

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

Group Type: EXPERIMENTAL

Basiliximab, Tacrolimus, MMF

Intervention Type: DRUG

No Prednisolon after 7 days

C

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

Group Type: EXPERIMENTAL

Tacrolimus, MMF, rATG

Intervention Type: DRUG

Induction therapy: rATG instead of Basiliximab. No Prednisolon.

Interventions

Basiliximab, Tacrolimus, MMF, Prednisolon

Control group. Therapy with Prednisolon.

Intervention Type: DRUG

Basiliximab, Tacrolimus, MMF

No Prednisolon after 7 days

Intervention Type: DRUG

Tacrolimus, MMF, rATG

Induction therapy: rATG instead of Basiliximab. No Prednisolon.

Intervention Type: DRUG

Other Intervention Names

Simulect; Advagraf; CellCept; Decortin; Simulect; Advagraf; CellCept; Advagraf; CellCept; Thymoglobulin

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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).
• Patients who possibly depend on the sponsor or the trial physician
• Patients with signs of drug abuse or alcohol abuse
• Patients taking additional medicines with known interactions with the immune suppressive substances (MMF and tacrolimus) that preclude an adequate control of the immunosuppression
• Cold ischemia time of donor kidney > 30 hours
• Pregnant or nursing patients

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roche Pharma AG

INDUSTRY

Sponsor Role: collaborator

Astellas Pharma GmbH

INDUSTRY

Sponsor Role: collaborator

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: collaborator

University Hospital Freiburg

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr.med. Oliver Thomusch

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ulrich Hopt, Prof.Dr.Dr.

Role: STUDY_DIRECTOR

University Hospital Freiburg

Oliver Thomusch, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Freiburg

Christian Hugo, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Universitaetsklinikum Erlangen

Locations

Universitaetsklinikum Würzburg

Würzburg, , Germany

Universitaetsklinikum der WWU Münster

Münster, , Germany

Universitätsklinikum Regensburg

Regensburg, , Germany

Universitätsklinikum Rostock

Rostock, , Germany

Universitätsklinikum Tübingen

Tübingen, , Germany

Klinikum rechts der Isar der TU München

München, , Germany

Universitaetsklinikum Berlin

Berlin, , Germany

Universitaetsklinikum Bonn

Bonn, , Germany

Klinikum Bremen-Mitte

Bremen, , Germany

Universitaetsklinikum Koeln

Cologne, , Germany

Kliniken der Stadt Köln gGmbH - Krankenhaus Köln-Merheim

Cologne, , Germany

Carl Gustav Carus Universitätsklinikum

Dresden, , Germany

Universitaetsklinikum Erlangen

Erlangen, , Germany

Universitaetsklinikum Essen

Essen, , Germany

Universitätsklinikum Frankfurt

Frankfurt am Main, , Germany

Universitaetsklinikum Freiburg

Freiburg im Breisgau, , Germany

Nephrologisches Zentrum Niedersachsen

Hannoversch Münden, , Germany

Universitätsklinikum Heidelberg

Heidelberg, , Germany

Universitätsklinikum Jena

Jena, , Germany

Transplantationszentrum Kaiserslautern

Kaiserslautern, , Germany

Universitätsklinikum Leipzig

Leipzig, , Germany

Universitätsklinikum Schleswig-Holstein Campus Lübeck

Lübeck, , Germany

Universitätsklinikum Mainz

Mainz, , Germany

Universitaetsklinikum Mannheim

Mannheim, , Germany

Universitätsklinikum München LMU

München, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 39382091 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37391381 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31029086 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27871759 (View on PubMed)

Other Identifiers

EudraCT No. 2007-006516-31

Identifier Type: -

Identifier Source: secondary_id

DRKS00000452

Identifier Type: REGISTRY

Identifier Source: secondary_id

IT1850071

Identifier Type: -

Identifier Source: org_study_id