Quinolone prophylaxis for the prevention of BK virus infection in kidney transplantation: study protocol for a randomized controlled trial

Trials

Greg A Knoll⁴  Tim Ramsay^1,10  Martin Karpinski⁹  Marcelo Cantarovich⁷  Jeff Zaltzman⁵  S Joseph Kim²  Sandra Cockfield⁸  Louise Lebel^1,10  Andrew A House⁶  Dean Fergusson^1,10  Olwyn Johnston³  John Gill¹  Atul Humar⁸ 

[1] Department of Medicine, St Paul’s Hospital, 1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada;Department of Medicine, Toronto General Hospital, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada;Department of Medicine, Vancouver General Hospital, 855 West 12th Avenue, Vancouver, BC V5Z 1M9, Canada;Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, 1967 Riverside Drive, Ottawa, ON K1H 7W9, Canada;Department of Medicine, St Michael’s Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada;Department of Medicine, Western University and London Health Sciences Centre, 339 Windermere Road, London, ON N6A 5A5, Canada;Department of Medicine, McGill University Health Center, 687 Pine Avenue West, Montreal, QC H3A 1A1, Canada;Department of Medicine, Faculty of Medicine & Dentistry, 2J2.00 WC Mackenzie Health Sciences Centre, University of Alberta, Edmonton, AB T6G 2R7, Canada;Department of Medicine, University of Manitoba, 820 Sherbrook Street, Winnipeg, MB R3T 2N2, Canada;Clinical Epidemiology Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada

关键词: Randomized controlled trial;    Levofloxacin;    Quinolone;    Polyomavirus;    BK virus;    Kidney transplantation;   

Others  :  1093632
DOI  :  10.1186/1745-6215-14-185

 received in 2013-04-02, accepted in 2013-06-06,  发布年份 2013

【 摘 要 】

Background

BK virus infection has emerged as a major complication in kidney transplantation leading to a significant reduction in graft survival. There are currently no proven strategies to prevent or treat BK virus infection. Quinolone antibiotics, such as levofloxacin, have demonstrated activity against BK virus. We hypothesize that administration of a quinolone antibiotic, when given early post-transplantation, will prevent the establishment of BK viral replication in the urine and thus prevent systemic BK virus infection.

Methods/design

The aim of this pilot trial is to assess the efficacy, safety and feasibility of a 3-month course of levofloxacin in the kidney transplant population. This is a multicenter, randomized, double-blind, placebo-controlled trial with two parallel arms conducted in 11 Canadian kidney transplant centers. A total of 154 patients with end-stage renal disease undergoing kidney transplantation will be randomized to receive a 3-month course of levofloxacin or placebo starting in the early post-transplant period. Levofloxacin will be administered at 500 mg po daily with dose adjustments based on kidney function. The primary outcome will be the time to occurrence of BK viruria within the first year post-transplantation. Secondary outcomes include BK viremia, measures of safety (adverse events, resistant infections,Clostridium difficile-associated diarrhea), measures of feasibility (proportion of transplanted patients recruited into the trial), proportion of patients adherent to the protocol, patient drop-out and loss to follow-up,and use of quinolone antibiotics outside of the trial protocol.

Discussion

Results from this pilot study will provide vital information to design and conduct a large, multicenter trial to determine if quinolone therapy decreases clinically meaningful outcomes in kidney transplantation. If levofloxacin significantly reduces BK viruria and urine viral loads in kidney transplantation, it will provide important justification to progress to the larger trial. If the full trial shows that levofloxacin significantly reduces BK infection and improves outcomes, its use in kidney transplantation will be strongly endorsed given the lack of proven therapies for this condition.

Trial registration

This trial was funded by the Canadian Institutes of Health Research (grant number:222493) and is registered at ClinicalTrials.gov ( NCT01353339).

【 授权许可】

   
2013 Humar et al.; licensee BioMed Central Ltd.

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