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Clinical Trial Details — Status: Withdrawn

Administrative data

NCT number NCT02758288
Other study ID # 5150278
Secondary ID
Status Withdrawn
Phase
First received
Last updated
Start date September 2015
Est. completion date July 2022

Study information

Verified date October 2020
Source Loma Linda University
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

The investigator's aim in this study is to evaluate the impact of a new standard of care protocol for the treatment of BK viremia and nephropathy (BKVAN), which includes switching from Tacrolimus to equivalent dose of Cyclosporine in patients who have been diagnosed with BK viremia or BKVAN based on their viral load, overall graft function (estimated glomerular filtration rate), acute rejection, and rate of graft loss due to rejection or BKVAN.


Description:

This study will be a combined retrospective chart review and prospective observational study. This will be a single center project that will take place at Loma Linda University Transplant Institute. All adult kidney recipients who are determined to have BK viremia with a BK PCR viral load over 500 copy post-transplant and meet the inclusion criteria but no exclusion criteria will be enrolled and observed per study protocol.

All kidney transplant recipients are routinely assessed for BK virus nephropathy and viremia post transplant as part of their standard care. Patients with BK viremia or BK virus nephropathy will have adjustments in their immunosuppressive medication based on current guidelines and recommendations which include reduction in immunosuppression, treatment with medications with antiviral activity (Cidofovir, Ciprofloxacin, Leflunomide, IVIG) or switching from a Tacrolimus (Prograf)-based regimen to a Cyclosporine-based regimen. Retrospectively, the investigator will collect data on patients who have been diagnosed with BK viremia or BK virus nephropathy and have had such a management in past 66 months (from 1/1/2010 till 06/30/2015). Prospectively, the investigator will enroll and collect data on patients who will be treated for BK viremia or BK virus nephropathy.

As standard of care, all kidney transplant recipients will be seen routinely on weekly-biweekly basis in post-transplant clinic for up to 3 months then every 3 months for up to a year and yearly thereafter. All kidney transplant recipients will be monitored for BK viremia by having blood PCR tested on a monthly basis at 1, 2, 3, 6, and 12 months after transplant. Also, all patients post-kidney transplant will be tested for BK viremia if there is an acute rise in their creatinine.


Recruitment information / eligibility

Status Withdrawn
Enrollment 0
Est. completion date July 2022
Est. primary completion date July 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria:

- Age = 18 years

- Recipient of kidney or combined kidney and pancreas

- BK viremia confirmed with blood PCR test with viral load over 500

- BK virus nephropathy confirmed by kidney biopsy

Exclusion Criteria:

- Recipient of combined organ transplant except kidney and pancreases

- Patient age < 18 years

- If patient does not consent for kidney biopsy

- Currently on treatment for acute rejection

- Patients with HIV, Hep C or Hep B infection

- Patients who are on other immunosuppression beside our standard regimen which includes Prograf, cellcept / Myfortic and prednisone

Study Design


Intervention

Other:
New Protocol - BK viremia or BK virus nephropathy
Data collected prospectively that will follow new clinical practice guidelines that were developed by Loma Linda Nephrology group with collaboration with Transplant surgeons to improve care of patients complicated with BK viremia or BK virus nephropathy.
Standard Protocol - BK viremia or BK virus nephropathy
Data collected retrospectively that followed standard clinical practice guidelines that were developed by Loma Linda Nephrology group with collaboration with Transplant surgeons to improve care of patients complicated with BK viremia or BK virus nephropathy.

Locations

Country Name City State
United States Loma Linda University Medical Center Loma Linda California

Sponsors (1)

Lead Sponsor Collaborator
Loma Linda University

Country where clinical trial is conducted

United States, 

References & Publications (47)

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Han SB, Cho B, Kang JH. BK virus-associated hemorrhagic cystitis after pediatric stem cell transplantation. Korean J Pediatr. 2014 Dec;57(12):514-9. doi: 10.3345/kjp.2014.57.12.514. Epub 2014 Dec 31. Review. — View Citation

Hariharan S. BK virus nephritis after renal transplantation. Kidney Int. 2006 Feb;69(4):655-62. Review. — View Citation

Hirsch HH, Randhawa P; AST Infectious Diseases Community of Practice. BK virus in solid organ transplant recipients. Am J Transplant. 2009 Dec;9 Suppl 4:S136-46. doi: 10.1111/j.1600-6143.2009.02904.x. — View Citation

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Hirsch HH, Vincenti F, Friman S, Tuncer M, Citterio F, Wiecek A, Scheuermann EH, Klinger M, Russ G, Pescovitz MD, Prestele H. Polyomavirus BK replication in de novo kidney transplant patients receiving tacrolimus or cyclosporine: a prospective, randomized, multicenter study. Am J Transplant. 2013 Jan;13(1):136-45. doi: 10.1111/j.1600-6143.2012.04320.x. Epub 2012 Nov 8. — View Citation

Hoppe-Seyler K, Sauer P, Lohrey C, Hoppe-Seyler F. The inhibitors of nucleotide biosynthesis leflunomide, FK778, and mycophenolic acid activate hepatitis B virus replication in vitro. Hepatology. 2012 Jul;56(1):9-16. doi: 10.1002/hep.25602. Epub 2012 Jun 1. — View Citation

Huang G, Chen LZ, Qiu J, Wang CX, Fei JG, Deng SX, Li J, Chen GD, Zhang L, Fu Q, Zeng WT, Zhao DQ. Prospective study of polyomavirus BK replication and nephropathy in renal transplant recipients in China: a single-center analysis of incidence, reduction in immunosuppression and clinical course. Clin Transplant. 2010 Sep-Oct;24(5):599-609. doi: 10.1111/j.1399-0012.2009.01141.x. — View Citation

Israni AK, Salkowski N, Gustafson S, Snyder JJ, Friedewald JJ, Formica RN, Wang X, Shteyn E, Cherikh W, Stewart D, Samana CJ, Chung A, Hart A, Kasiske BL. New national allocation policy for deceased donor kidneys in the United States and possible effect on patient outcomes. J Am Soc Nephrol. 2014 Aug;25(8):1842-8. doi: 10.1681/ASN.2013070784. Epub 2014 May 15. — View Citation

Johnston TD, Thacker LR, Jeon H, Lucas BA, Ranjan D. Sensitivity of expanded-criteria donor kidneys to cold ischaemia time. Clin Transplant. 2004;18 Suppl 12:28-32. — View Citation

Kadambi PV, Josephson MA, Williams J, Corey L, Jerome KR, Meehan SM, Limaye AP. Treatment of refractory BK virus-associated nephropathy with cidofovir. Am J Transplant. 2003 Feb;3(2):186-91. — View Citation

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Knoll GA, Bell RC. Tacrolimus versus cyclosporin for immunosuppression in renal transplantation: meta-analysis of randomised trials. BMJ. 1999 Apr 24;318(7191):1104-7. — View Citation

Leung AY, Chan MT, Yuen KY, Cheng VC, Chan KH, Wong CL, Liang R, Lie AK, Kwong YL. Ciprofloxacin decreased polyoma BK virus load in patients who underwent allogeneic hematopoietic stem cell transplantation. Clin Infect Dis. 2005 Feb 15;40(4):528-37. Epub 2005 Jan 21. — View Citation

Mateo R, Cho Y, Singh G, Stapfer M, Donovan J, Kahn J, Fong TL, Sher L, Jabbour N, Aswad S, Selby RR, Genyk Y. Risk factors for graft survival after liver transplantation from donation after cardiac death donors: an analysis of OPTN/UNOS data. Am J Transplant. 2006 Apr;6(4):791-6. — View Citation

Matsuoka L, Shah T, Aswad S, Bunnapradist S, Cho Y, Mendez RG, Mendez R, Selby R. Pulsatile perfusion reduces the incidence of delayed graft function in expanded criteria donor kidney transplantation. Am J Transplant. 2006 Jun;6(6):1473-8. — View Citation

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Moscarelli L, Caroti L, Antognoli G, Zanazzi M, Di Maria L, Carta P, Minetti E. Everolimus leads to a lower risk of BKV viremia than mycophenolic acid in de novo renal transplantation patients: a single-center experience. Clin Transplant. 2013 Jul-Aug;27(4):546-54. doi: 10.1111/ctr.12151. Epub 2013 Jun 13. — View Citation

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. Review. — View Citation

Nickeleit V, Klimkait T, Binet IF, Dalquen P, Del Zenero V, Thiel G, Mihatsch MJ, Hirsch HH. Testing for polyomavirus type BK DNA in plasma to identify renal-allograft recipients with viral nephropathy. N Engl J Med. 2000 May 4;342(18):1309-15. — View Citation

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Randhawa P, Ho A, Shapiro R, Vats A, Swalsky P, Finkelstein S, Uhrmacher J, Weck K. Correlates of quantitative measurement of BK polyomavirus (BKV) DNA with clinical course of BKV infection in renal transplant patients. J Clin Microbiol. 2004 Mar;42(3):1176-80. — View Citation

Randhawa PS. Anti-BK virus activity of ciprofloxacin and related antibiotics. Clin Infect Dis. 2005 Nov 1;41(9):1366-7; author reply 1367. — View Citation

Renner FC, Dietrich H, Bulut N, Celik D, Freitag E, Gaertner N, Karoui S, Mark J, Raatz C, Weimer R, Feustel A. The risk of polyomavirus-associated graft nephropathy is increased by a combined suppression of CD8 and CD4 cell-dependent immune effects. Transplant Proc. 2013 May;45(4):1608-10. doi: 10.1016/j.transproceed.2013.01.026. — View Citation

Rinaldo CH, Tylden GD, Sharma BN. The human polyomavirus BK (BKPyV): virological background and clinical implications. APMIS. 2013 Aug;121(8):728-45. doi: 10.1111/apm.12134. Epub 2013 Jun 19. Review. — View Citation

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* Note: There are 47 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Kidney function to compare effectiveness of a new care protocol for the treatment of BK viremia (BK PCR viral load over 500 copy) and BKVAN (confirmed by kidney biopsy) with a similar cohort treated with traditional methods. 12 months
Secondary Rate of BK nephropathy in both treatment groups confirmed by kidney biopsy 24 months
Secondary Rate of acute cellular or humoral rejection in both treatment groups confirmed by kidney biopsy 24 months
Secondary Rate of graft loss in both group as determined by elevated creatinine level and kidney biopsy 24 months
Secondary Estimated glomerular filtration rate (eGFR) at start of the study (0) , 3, 6, 12 and 24 months between two groups 3, 6, 12, 24 months
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