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

This study has been completed.
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
St. Paul's Hospital, Canada
Vancouver General Hospital
University of Alberta
University of Manitoba
University Health Network, Toronto
St. Michael's Hospital, Toronto
St. Joseph's Healthcare Hamilton
London Health Sciences Centre
McGill University Health Center
Dalhousie University
Information provided by (Responsible Party):
Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:
NCT01353339
First received: May 11, 2011
Last updated: October 14, 2014
Last verified: October 2014

May 11, 2011
October 14, 2014
November 2011
April 2014   (final data collection date for primary outcome measure)
Efficacy: The time to occurence of BK viruria [ Time Frame: 12 months post-transplantation ] [ Designated as safety issue: No ]
BK viruria will be defined as ≥1000 copies/mL ok BK virus DNA in the urine.
Same as current
Complete list of historical versions of study NCT01353339 on ClinicalTrials.gov Archive Site
  • Adverse Events [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Incidence and type of all adverse events
  • Acute rejection [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Incidence of Acute rejection
  • Clostridium difficile associated diarrhea [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Incidence of microbiologically confirmed clostridium difficile associated diarrhea
  • Infections [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Incidence of other infections (viral, bacterial and fungal) based on established guidelines
  • Quinolone resistance [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Incidence of quinolone resistance where a quinolone would have been a therapeutic option
  • Effect of levofloxacin on immunosuppressive drug doses and blood levels [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Transplant failure [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Mortality [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Number of patients transplanted [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Number of patients transplanted during the 8 month recruitment period who are randomized into the trial
  • Adherence [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Proportion of randomized participants who are adherent to the protocol.
  • Use of quinolones [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Use of quinolones outside of the protocol
  • Proportion of patient drop-out and loss to follow-up [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Quantitative BK urine viral load [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • BK viremia [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Time to occurence of BK viremia, defined as ≥250 copies/mL of BK virus DNA in the plasma
  • Adverse Events [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Incidence and type of all adverse events
  • Acute rejection [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Incidence of Acute rejection
  • Clostridium difficile associated diarrhea [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Incidence of microbiologically confirmed clostridium difficile associated diarrhea
  • Infections [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Incidence of other infections (viral, bacterial and fungal) based on establised guidelines
  • Quinolone resistance [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Incidence of quinolone resistance where a quinolone would have been a therapeutic option
  • Effect of levofloxacin on immunosuppressive drug doses and blood levels [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Transplant failure [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Mortality [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Number of patients transplanted [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Number of patients transplanted during the 8 month recruitment period who are randomized into the trial
  • Adherence [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Proportion of randomized participants who are adherent to the protocol.
  • Use of quinolones [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Use of quinolones outside of the protocol
  • Proportion of patient drop-out and loss to follow-up [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Quantitative BK urine viral load [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • BK viremia [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Time to occurence of BK viremia, defined as ≥250 copies/mL of BK virus DNA in the plasma
Not Provided
Not Provided
 
Quinolone Prophylaxis for the Prevention of BK Virus Infection in Kidney Transplantation: A Pilot Study
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

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
  • Disease Due to BK Polyomavirus
  • Kidney Transplant Infection
Drug: Levofloxacin
500mg, PO, once daily for 3 months
Other Names:
  • Apo-levofloxacin
  • DIN 02284707
  • Placebo Comparator: sugar pill
    Intervention: Drug: Levofloxacin
  • Active Comparator: levofloxacin
    Intervention: Drug: Levofloxacin
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
154
October 2014
April 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT01353339
CIHR MOP 222493, 2010-292
Yes
Ottawa Hospital Research Institute
Ottawa Hospital Research Institute
  • Canadian Institutes of Health Research (CIHR)
  • St. Paul's Hospital, Canada
  • Vancouver General Hospital
  • University of Alberta
  • University of Manitoba
  • University Health Network, Toronto
  • St. Michael's Hospital, Toronto
  • St. Joseph's Healthcare Hamilton
  • London Health Sciences Centre
  • McGill University Health Center
  • Dalhousie University
Principal Investigator: Greg Knoll, MD Ottawa Hospital Research Institute
Ottawa Hospital Research Institute
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP