Quinolone Prophylaxis for the Prevention of BK Virus Infection in Kidney Transplantation: A Pilot Study

Primary Research Questions:

Efficacy, safety and feasibility of a 3-month course of levofloxacin in a pilot study will be assessed.

1. Under efficacy, this pilot will determine whether levofloxacin can decrease the incidence of BK viruria and peak urine BK viral load.
2. Under safety, this pilot will determine the incidence of adverse events with levofloxacin.
3. Under feasibility, this pilot will determine the number of kidney transplant patients randomized over an eight month enrolment period, adherence to the levofloxacin and frequency of patient drop-out and loss to follow-up

Study Overview

• Status: Completed
• Conditions: Kidney Transplant Infection; Disease Due to BK Polyomavirus
• Intervention / Treatment: Drug: Levofloxacin

Detailed Description

BK virus infection has emerged as a major complication in renal 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. The investigators 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. A non-randomized study in kidney transplant recipients found that patients given levofloxacin or ciprofloxacin had a significantly lower incidence of BK viremia compared to those not receiving a quinolone (4% versus 24.5%, P=0.02).

Objective: The primary objective of the full trial will be to determine if the quinolone levofloxacin decreases the occurrence of doubling creatinine, transplant failure or death in kidney transplant recipients. 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.

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

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Capital Health - University of Alberta Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada
      • Winnipeg Health Science Center
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
      • Qeii Health Science Center
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare
    • London, Ontario, Canada, N6A 5A5
      • London Health Science Center
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital
    • Toronto, Ontario, Canada, M5G 2N2
      • University Health Network
    • Toronto, Ontario, Canada
      • St. Michael's Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • McGill University Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• a primary or repeat kidney transplant recipient (deceased or living donor)
• age greater or equal to 18 years

Exclusion Criteria:

• Unable to provide informed consent
• Greater than 5 days post-transplantation
• BK virus nephropathy with a previous transplant
• History of allergic reaction to any quinolone antibiotic
• History of quinolone associated tendonitis or tendon rupture
• Corrected QT interval prolongation on EKG as defined by Al-Khatib
• Concomitant use of medication known to prolong the QT interval such as class IA antiarrhythmic drugs (e.g. quinidine, procainamide, disopyramide), class III antiarrhythmic drugs (e.g. amiodarone, sotalol), azole antifungals (e.g. fluconazole) or macrolide antibiotics (e.g. erythromycin)
• Pregnant or breastfeeding as safety of levofloxacin not established
• Requires quinolone antibiotic for more than 14 days (e.g. for UTI prophylaxis)
• Recipient of a multi-organ transplant (e.g. kidney-pancreas)
• Currently enrolled in another interventional trial
• Previously enrolled in this study
• History of rhabdomyolysis
• Significant allergic reaction to ≥ 3 classes of antibiotics as these patients may have no other option other than quinolones for routine infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: sugar pill	Drug: Levofloxacin; 500mg, PO, once daily for 3 months; Other Names: Apo-levofloxacin; DIN 02284707
Active Comparator: levofloxacin	Drug: Levofloxacin; 500mg, PO, once daily for 3 months; Other Names: Apo-levofloxacin; DIN 02284707

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of BK Viruria	BK viruria was defined as 500 copies/mL or more of BK virus DNA in the urine.	12 months post-transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Incidence and type of all adverse events	12 months
Infections	Incidence of other infections (viral, bacterial and fungal) based on established guidelines	12 months
Mortality		12 months
Adherence	Proportion of randomized participants who are adherent to the protocol.	12 months
Acute Rejection	Incidence of Acute rejection	12 months
Clostridium Difficile Associated Diarrhea	Incidence of microbiologically confirmed clostridium difficile associated diarrhea	12 months
Quinolone Resistance	Incidence of quinolone resistance where a quinolone would have been a therapeutic option	12 months
Allograft Loss	Absence of kidney function in allograft	12 months
Use of Quinolones	Use of quinolones outside of the protocol	12 months
Proportion of Patient Drop-out and Loss to Follow-up		12 months
Quantitative BK Urine Viral Load		12 months
BK Viremia	BK viremia defined as ≥250 copies/mL of BK virus DNA in the plasma	12 months

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Collaborators: University of Manitoba; St. Joseph's Healthcare Hamilton; University Health Network, Toronto; Canadian Institutes of Health Research (CIHR); University of Alberta; McGill University Health Centre/Research Institute of the McGill University Health Centre; Unity Health Toronto; Dalhousie University; London Health Sciences Centre; St. Paul's Hospital, Canada; Vancouver General Hospital
• Investigators: Principal Investigator: Greg Knoll, MD, Ottawa Hospital Research Institute

Publications and helpful links

General Publications

• Knoll GA, Humar A, Fergusson D, Johnston O, House AA, Kim SJ, Ramsay T, Chasse M, Pang X, Zaltzman J, Cockfield S, Cantarovich M, Karpinski M, Lebel L, Gill JS. Levofloxacin for BK virus prophylaxis following kidney transplantation: a randomized clinical trial. JAMA. 2014 Nov 26;312(20):2106-14. doi: 10.1001/jama.2014.14721.
• Humar A, Gill J, Johnston O, Fergusson D, House AA, Lebel L, Cockfield S, Kim SJ, Zaltzman J, Cantarovich M, Karpinski M, Ramsay T, Knoll GA. Quinolone prophylaxis for the prevention of BK virus infection in kidney transplantation: study protocol for a randomized controlled trial. Trials. 2013 Jun 21;14:185. doi: 10.1186/1745-6215-14-185.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2011
• Primary Completion (Actual): February 25, 2014
• Study Completion (Actual): February 25, 2014

Study Registration Dates

• First Submitted: May 11, 2011
• First Submitted That Met QC Criteria: May 12, 2011
• First Posted (Estimated): May 13, 2011

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: October 11, 2023
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Kidney Transplant; BK Polyomavirus Infection
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Virus Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Anti-Infective Agents, Urinary; Levofloxacin; Ofloxacin
• Other Study ID Numbers: CIHR MOP 222493, 2010-292

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No