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Disorder Related to Renal TransplantationPhase 4HarmonyNCT00724022

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

A Phase 4 study testing Basiliximab, Tacrolimus, MMF, Prednisolon, Basiliximab, Tacrolimus, MMF and Tacrolimus, MMF, rATG in people with Disorder Related to Renal Transplantation, run by University Hospital Freiburg at 25 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Basiliximab, Tacrolimus, MMF, Prednisolon, Basiliximab, Tacrolimus, MMF and Tacrolimus, MMF, rATG
Could I receive a placebo?
No, everyone receives an active treatment
How many people
600 participants
Where
25 sitesGermany
Study dates
Jun 2008to Jul 2014
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 20Show fewer
  • 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

Trial locations and contacts

25 sites in 1 country.

25 sites in 1 country

Germany25 sites

  • Universitaetsklinikum Berlin

    Berlin, 13353

  • Universitaetsklinikum Bonn

    Bonn, 53105

  • Klinikum Bremen-Mitte

    Bremen, 28177

  • Universitaetsklinikum Koeln

    Cologne, 50924

  • Kliniken der Stadt Köln gGmbH - Krankenhaus Köln-Merheim

    Cologne, 51109

  • Carl Gustav Carus Universitätsklinikum

    Dresden, 01307

  • Universitaetsklinikum Erlangen

    Erlangen, 91054

  • Universitaetsklinikum Essen

    Essen, 45122

  • Universitätsklinikum Frankfurt

    Frankfurt am Main, 60590

  • Universitaetsklinikum Freiburg

    Freiburg im Breisgau, 79106

  • Nephrologisches Zentrum Niedersachsen

    Hannoversch Münden, 34346

  • Universitätsklinikum Heidelberg

    Heidelberg, 69120

  • Universitätsklinikum Jena

    Jena, 07747

  • Transplantationszentrum Kaiserslautern

    Kaiserslautern, 67655

  • Universitätsklinikum Leipzig

    Leipzig, 04103

  • Universitätsklinikum Schleswig-Holstein Campus Lübeck

    Lübeck, 23538

  • Universitätsklinikum Mainz

    Mainz, 55131

  • Universitaetsklinikum Mannheim

    Mannheim, 68167

  • Universitätsklinikum München LMU

    München, 81377

  • Klinikum rechts der Isar der TU München

    München, 81675

  • Universitaetsklinikum der WWU Münster

    Münster, 48149

  • Universitätsklinikum Regensburg

    Regensburg, 93053

  • Universitätsklinikum Rostock

    Rostock, 18057

  • Universitätsklinikum Tübingen

    Tübingen, 72076

  • Universitaetsklinikum Würzburg

    Würzburg, 97080

Other trials in Germany

About this study

Official title: Triple Arm, Prospectively Randomized Multi Centre Study Phase IV to Evaluate Calcineurin Inhibitor Reduced, Steroid Free Immunosuppression After Renal Transplantation in Non-risk Patients

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.

Read the 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).

Being tested
Basiliximab, Tacrolimus, MMF, Prednisolon, Basiliximab, Tacrolimus, MMF, Tacrolimus, MMF, rATG
Keywords
Kidney transplant status, Steroid free, Reduced, Calcineurin, Inhibitor, Immunosuppression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Basiliximab, Tacrolimus, MMF, PrednisolonDrug

    Also called Simulect, Advagraf, CellCept, Decortin

    Control group. Therapy with Prednisolon.

  • Basiliximab, Tacrolimus, MMFDrug

    Also called Simulect, Advagraf, CellCept

    No Prednisolon after 7 days

  • Tacrolimus, MMF, rATGDrug

    Also called Advagraf, CellCept, Thymoglobulin

    Induction therapy: rATG instead of Basiliximab. No Prednisolon.

Study groups in NCT00724022
Study groupRoleWhat they receive
AOtherStandard: Advagraf, CellCept, Decortin H + 2x Simulect Day 0 + 4
Receives: Drug: Basiliximab, Tacrolimus, MMF, Prednisolon
BExperimentalSteroidfree: Advagraf, Cellcept, Decortin H until Day 8, 2x Simulect Day 0 + 4
Receives: Drug: Basiliximab, Tacrolimus, MMF
CExperimentalSteroidfree: Advagraf, Cellcept, Decortin H until Day 8, 3 x Thymoglobulin
Receives: Drug: Tacrolimus, MMF, rATG

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: one year after transplantation

Secondary outcomes (20)

  1. Rate of patients with steroid-free immunosuppression

    Rate of patients with steroid-free immunosuppression

  2. patient and graft survival rate

    patient and graft survival rate

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

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

  4. Number of steroid-resistant rejections

    Number of steroid-resistant rejections

  5. blood pressure level and also amount and types of blood pressure medications

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

  6. Lipid levels and also amount and types of lipid-lowering medications

    Lipid levels and also amount and types of lipid-lowering medications

  7. body weight, relative weight gain [kg], BMI

    body weight, relative weight gain [kg], BMI

  8. infection rate, infection type and infection severity

    infection rate, infection type and infection severity

  9. anemia requiring erythropoietin treatment

    anemia requiring erythropoietin treatment

  10. PTLD incidence

    PTLD incidence

  11. tumor incidence

    tumor incidence

  12. incidence of diabetes mellitus nd incidence of abnormal fasting blood sugar levels respectively incidence of impaired glucose tolerance, incidence of de novo insulin-requiring or oral-antidiabetic-requiring treatment over ≥30 days

    incidence of diabetes mellitus (ADA criteria, venous blood glucose concentration on an empty stomach ≥7.0 mmol/l, pathologic OGTT) and incidence of abnormal fasting blood sugar levels respectively incidence of impaired glucose tolerance, incidence of de novo insulin-requiring or oral-antidiabetic-requiring treatment over ≥30 days

    Measured: 30 days

  13. incidence of cataracts

    incidence of cataracts

  14. incidence of avascular necrosis

    incidence of avascular necrosis

  15. incidence of osteoporosis

    incidence of osteoporosis (assessment of fracture rate, osteodensitometry)

  16. Wound healing disorders

    Wound healing disorders

  17. incidence of chronic allograft nephropathy (CAN) (12-month histology)

    incidence of chronic allograft nephropathy (CAN) (12-month histology)

  18. incidence of CMV disease (qPCR >1000 copies/μL)

    incidence of CMV disease (qPCR >1000 copies/μL)

  19. incidence of BKV disease (qPCR >1000 copies/μL)

    incidence of BKV disease (qPCR >1000 copies/μL)

  20. incidence of EBV disease (qPCR >1000 copies/μL)

    incidence of EBV disease (qPCR >1000 copies/μL)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jul 2008 (estimated)
  2. Study startJun 2008
  3. Primary completionJul 2014
  4. Study completionJul 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
600 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00724022
Sponsor's protocol ID
IT1850071
Other IDs
EudraCT No. 2007-006516-31, DRKS00000452
Acronym
Harmony
Status last verified
Sep 2014
First submitted
25 Jul 2008
Last updated
1 Oct 2014
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 39382091

  • 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.

    PubMed 37391381

  • 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.

    PubMed 31029086

  • 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.

    PubMed 27871759

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Basiliximab, Tacrolimus, MMF, Prednisolon, Basiliximab, Tacrolimus, MMF and Tacrolimus, MMF, rATG in people with Disorder Related to Renal Transplantation, run by University Hospital Freiburg at 25 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy of immunosuppression measured in rejection rate confirmed by biopsy according to BANFF 97, modified 2005. (time frame: one year after transplantation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00724022, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2014.

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