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Polyomavirus InfectionsPhase 4NCT00160966

Impact of Immunosuppressive Regimens on Polyomavirus-related Transplant Nephropathy

A Phase 4 study testing Ciclosporin and Mycophenolate-mofetil, Tacrolimus and Mycophenolate-mofetil and Tacrolimus and Mycophenolate-mofetil with change from Mycophenolate-mofetil to Everolimus in people with Polyomavirus Infections, run by University of Giessen at 1 site in Germany.

Completed

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

Official record
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Trial summary

The aim of this study is to characterize and evaluate risk factors of polyomavirus nephropathy (PVN) including the impact of three immunosuppressive regimens. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Polyomavirus Infections
What is being tested?
Ciclosporin and Mycophenolate-mofetil, Tacrolimus and Mycophenolate-mofetil and Tacrolimus and Mycophenolate-mofetil with change from Mycophenolate-mofetil to Everolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
108 participants
Where
1 siteGermany
Study dates
Sep 2004to Mar 2010
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Cadaver kidney and living donor kidney transplant recipients
  • Primary, secondary, and tertiary transplant recipients
  • Pre-immunized and not pre-immunized transplant recipients
  • Age > 18 years

Who cannot join

  • Contraindications against administration of one of the four study drugs
  • History of severe gastrointestinal morbidity
  • Age < 18 years
  • Pregnant or breast feeding women
  • Rejection of effective contraceptive methods with young women
  • Combined kidney and islet cell transplantation

Trial locations and contacts

1 site in 1 country.

Germany1 site
  • Department of Internal Medicine, University of Giessen

    Giessen, 35392

Other trials in Germany

About this study

Official title: Prospective Randomized Study to Characterize Risk Factors of Polyomavirus-related Transplant Nephropathy and the Impact of Three Immunosuppressive Regimens on Nephropathy Incidence

The aim of this study is to characterize and evaluate risk factors of polyomavirus nephropathy (PVN) including the impact of three immunosuppressive regimens.

Read the detailed description

Polyomavirus nephropathy (PVN) is an emerging cause of renal transplant loss. Until now the risk factors of PVN are poorly understood. Tacrolimus (Tacr) and mycophenolate mofetil (MMF) are thought to be associated with a higher risk of developing PVN. However, the way in which Tacr or MMF might enhance the susceptibility for PVN remains largely unknown. In this prospective study we will analyze whether differences in immune-reactivity patterns (Th1, Th2, B cell and monocyte responses, sCD30, immunoregulatory antibodies) of renal transplant patients induced by different immunosuppressive regimens (cyclosporine A [CsA]/MMF, Tacr/MMF, Tacr/MMF with conversion to Tacr/Everolimus [ERL]) or by cytokine promoter gene polymorphisms may account for the different risks of developing PVN.

Comparison(s): renal transplant recipients stratified according to their relative immunological risk (group 1: low risk (primary recipients without pre-immunization [PRA < 5%]); group 2: moderate risk (group 2a: primary recipients with low pre-immunization [PRA 6-20%]; group 2b: re-transplanted patients); group 3: very high risk (re-transplanted patients with a history of vascular rejection or recipients of a first graft with high pre-immunization [PRA > 20%]) randomized to be treated with one of three immunosuppressive regimens (CsA/MMF, Tacr/MMF, Tacr/MMF with subsequent conversion to Tacr/ERL).

Being tested
Ciclosporin and Mycophenolate-mofetil, Tacrolimus and Mycophenolate-mofetil, Tacrolimus and Mycophenolate-mofetil with change from Mycophenolate-mofetil to Everolimus
Keywords
kidney transplantation, polyoma virus associated transplant nephropathy, tacrolimus, mycophenolate mofetil, everolimus, cyclosporin A, BK virus PCR, viruria screening, BK polyomavirus, immunosuppression
Medical subject headings
Polyomavirus Infections

What participants receive

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

  • Ciclosporin and Mycophenolate-mofetilDrug

    according to the Giessen protocol

  • Tacrolimus and Mycophenolate-mofetilDrug

    according to Giessen protocol

  • Tacrolimus and Mycophenolate-mofetil with change from Mycophenolate-mofetil to EverolimusDrug

    according to Giessen protocol

Study groups in NCT00160966
Study groupRoleWhat they receive
1Active comparatorImmunosuppression with Ciclosporin and Mycophenolate-mofetil; Ciclosporin treatment being started at the latest at day 4 after transplantation with 7 mg/kg body weight daily administered every 8 hours until the target trough level of 300 µg/l was reached. Then it was administered twice daily with daily monitoring of trough levels. The target trough level was lowered to 200 µg/l 1 month after transplantation. Thereafter dosage and target trough levels were adjusted at the investigators discretion. Mycophenolate-mofetil was started previous to transplantation procedure with a starting dosage of 3 g/day administered twice daily. Once ciclosporin was entered into the therapy-scheme Mycophenolate-mofetil dosage was reduced to 2 g/daily. The therapy was controlled by measuring of trough levels with a target trough level exceeding 1 µg/ml. The dosage was adjusted at the investigators discretion.
Receives: Drug: Ciclosporin and Mycophenolate-mofetil
2Active comparatorImmunosuppression with Tacrolimus and Mycophenolate-mofetil Mycophenolate-mofetil was started previous to transplantation procedure with a starting dosage of 3 g/day administered twice daily. Once tacrolimus was entered into the therapy-scheme Mycophenolate-mofetil dosage was reduced to 2 g/daily. The therapy was controlled by measuring of trough levels with a target trough level exceeding 1 µg/ml. The dosage was adjusted to clinical signs of overimmunosuppression (infections) or intolerance (mainly gastrointestinal side effects) or rejections.
Receives: Drug: Tacrolimus and Mycophenolate-mofetil
3Active comparatorImmunosuppression with Tacrolimus and Mycophenolate-mofetil with change from Mycophenolate-mofetil to Everolimus after completion of posttransplant wound healing
Receives: Drug: Tacrolimus and Mycophenolate-mofetil with change from Mycophenolate-mofetil to Everolimus

What is being measured

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

  1. incidence of polyomavirus associated transplant nephropathy (PVN)

    Measured: 2 years posttransplant

  2. incidence of polyoma viremia

    Measured: 2 years posttransplant

  3. urine polyomavirus concentration within the first two years post-transplant

    Measured: 2 years posttransplant

Secondary outcomes (6)
  1. patients' and grafts' survival

    Measured: 2 years posttransplant

  2. incidence of acute rejections

    Measured: 2 years posttransplant

  3. transplant function 1 and 2 years post-transplant

    Measured: 2 years posttransplant

  4. comparison of urine cytology and polymerase chain reaction (PCR) quantitative data regarding diagnosis of PVN

    Measured: 2 years posttransplant

  5. predictive value of immune parameters prognostically relevant for acute or chronic rejection

    Measured: 2 years posttransplant

  6. side effects of immunosuppressive drugs

    Measured: 2 years posttransplant

Timeline

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

  1. First posted12 Sep 2005 (estimated)
  2. Study startSep 2004
  3. Primary completionMar 2010
  4. Study completionMar 2010

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
108 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00160966
Sponsor's protocol ID
NTx-PV-002
Status last verified
Jan 2017
First submitted
8 Sep 2005
Last updated
28 Mar 2017
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes: De-identified data of all participants will be made available within 1 year of study completion.

Publications

  • Andrews CA, Shah KV, Daniel RW, Hirsch MS, Rubin RH. A serological investigation of BK virus and JC virus infections in recipients of renal allografts. J Infect Dis. 1988 Jul;158(1):176-81. doi: 10.1093/infdis/158.1.176.

    PubMed 2839580
  • Barri YM, Ahmad I, Ketel BL, Barone GW, Walker PD, Bonsib SM, Abul-Ezz SR. Polyoma viral infection in renal transplantation: the role of immunosuppressive therapy. Clin Transplant. 2001 Aug;15(4):240-6. doi: 10.1034/j.1399-0012.2001.150404.x.

    PubMed 11683817
  • Nickeleit V, Hirsch HH, Zeiler M, Gudat F, Prince O, Thiel G, Mihatsch MJ. BK-virus nephropathy in renal transplants-tubular necrosis, MHC-class II expression and rejection in a puzzling game. Nephrol Dial Transplant. 2000 Mar;15(3):324-32. doi: 10.1093/ndt/15.3.324.

    PubMed 10692517
  • Hirsch HH, Knowles W, Dickenmann M, Passweg J, Klimkait T, Mihatsch MJ, Steiger J. Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients. N Engl J Med. 2002 Aug 15;347(7):488-96. doi: 10.1056/NEJMoa020439.

    PubMed 12181403
  • Hirsch HH. Polyomavirus BK nephropathy: a (re-)emerging complication in renal transplantation. Am J Transplant. 2002 Jan;2(1):25-30. doi: 10.1034/j.1600-6143.2002.020106.x.

    PubMed 12095052
  • Hirsch HH, Mohaupt M, Klimkait T. Prospective monitoring of BK virus load after discontinuing sirolimus treatment in a renal transplant patient with BK virus nephropathy. J Infect Dis. 2001 Dec 1;184(11):1494-5; author reply 1495-6. doi: 10.1086/324425. No abstract available.

    PubMed 11709797
  • Binet I, Nickeleit V, Hirsch HH, Prince O, Dalquen P, Gudat F, Mihatsch MJ, Thiel G. Polyomavirus disease under new immunosuppressive drugs: a cause of renal graft dysfunction and graft loss. Transplantation. 1999 Mar 27;67(6):918-22. doi: 10.1097/00007890-199903270-00022.

    PubMed 10199744
  • Weimer R, Susal C, Yildiz S, Streller S, Pelzl S, Staak A, Renner F, Dietrich H, Daniel V, Feuring E, Kamali-Ernst S, Ernst W, Padberg W, Opelz G. sCD30 and neopterin as risk factors of chronic renal transplant rejection: impact of cyclosporine A, tacrolimus, and mycophenolate mofetil. Transplant Proc. 2005 May;37(4):1776-8. doi: 10.1016/j.transproceed.2005.02.088.

    PubMed 15919463
  • Weimer R, Staak A, Susal C, Streller S, Yildiz S, Pelzl S, Renner F, Dietrich H, Daniel V, Rainer L, Kamali-Ernst S, Ernst W, Padberg W, Opelz G. ATG induction therapy: long-term effects on Th1 but not on Th2 responses. Transpl Int. 2005 Feb;18(2):226-36. doi: 10.1111/j.1432-2277.2004.00047.x.

    PubMed 15691277
  • Weimer R, Mytilineos J, Feustel A, Preiss A, Daniel V, Grimm H, Wiesel M, Opelz G. Mycophenolate mofetil-based immunosuppression and cytokine genotypes: effects on monokine secretion and antigen presentation in long-term renal transplant recipients. Transplantation. 2003 Jun 27;75(12):2090-9. doi: 10.1097/01.TP.0000058808.37349.23.

    PubMed 12829918
  • Weimer R, Streller S, Staak A, Heilke M, Li D, Dietrich H, Daniel V, Feustel A, Rainer L, Zinn S, Friemann S, Ernst W, Grimm H, Padberg W, Zimmermann T, Opelz G. Effects of three immunosuppressive regimens on CD4 helper function, B cell monocyte and cytokine responses in renal transplant recipients: 4-month follow-up of a prospective randomized study. Transplant Proc. 2002 Sep;34(6):2377-8. doi: 10.1016/s0041-1345(02)03278-5. No abstract available.

    PubMed 12270445
  • Weimer R, Melk A, Daniel V, Friemann S, Padberg W, Opelz G. Switch from cyclosporine A to tacrolimus in renal transplant recipients: impact on Th1, Th2, and monokine responses. Hum Immunol. 2000 Sep;61(9):884-97. doi: 10.1016/s0198-8859(00)00152-x.

    PubMed 11053632
  • Daniel V, Arzberger J, Melk A, Weimer R, Ruhenstroth A, Carl S, Wiesel M, Opelz G. Predictive indicators of rejection or infection in renal transplant patients. Transplant Proc. 1999 Feb-Mar;31(1-2):1364-5. doi: 10.1016/s0041-1345(98)02030-2. No abstract available.

    PubMed 10083605
  • Weimer R, Zipperle S, Daniel V, Carl S, Staehler G, Opelz G. Pretransplant CD4 helper function and interleukin 10 response predict risk of acute kidney graft rejection. Transplantation. 1996 Dec 15;62(11):1606-14. doi: 10.1097/00007890-199612150-00014.

    PubMed 8970616
  • Daniel V, Pasker S, Wiesel M, Carl S, Pomer S, Staehler G, Schnobel R, Weimer R, Opelz G. Cytokine monitoring of infection and rejection in renal transplant recipients. Transplant Proc. 1995 Feb;27(1):884-6. No abstract available.

    PubMed 7879219

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Ciclosporin and Mycophenolate-mofetil, Tacrolimus and Mycophenolate-mofetil and Tacrolimus and Mycophenolate-mofetil with change from Mycophenolate-mofetil to Everolimus in people with Polyomavirus Infections, run by University of Giessen at 1 site 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 4 inclusion and 6 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 28 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

incidence of polyomavirus associated transplant nephropathy (PVN) (time frame: 2 years posttransplant). The study lists 3 primary outcomes in all. 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 NCT00160966, which also lists 23 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 28 Mar 2017.

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