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

This study is ongoing, but not recruiting participants.
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: July 3, 2013
Last verified: July 2013
  Purpose

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

Condition Intervention Phase
Disease Due to BK Polyomavirus
Kidney Transplant Infection
Drug: Levofloxacin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Quinolone Prophylaxis for the Prevention of BK Virus Infection in Kidney Transplantation: A Pilot Study

Resource links provided by NLM:


Further study details as provided by Ottawa Hospital Research Institute:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 154
Study Start Date: November 2011
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01353339

Locations
Canada, Alberta
Capital Health - University of Alberta Hospital
Edmonton, Alberta, Canada, T6G 2B7
Canada, British Columbia
St. Paul's Hospital
Vancouver, British Columbia, Canada, V6Z 1Y6
Vancouver General Hospital
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, Manitoba
Winnipeg Health Science Center
Winnipeg, Manitoba, Canada
Canada, Nova Scotia
QEII Health Science Center
Halifax, Nova Scotia, Canada
Canada, Ontario
St. Joseph's Healthcare
Hamilton, Ontario, Canada, L8N 4A6
London Health Science Center
London, Ontario, Canada, N6A 5A5
The Ottawa Hospital
Ottawa, Ontario, Canada, K1H 8L6
University Health Network
Toronto, Ontario, Canada, M5G 2N2
St. Michael's Hospital
Toronto, Ontario, Canada
Canada, Quebec
McGill University Health Center
Montreal, Quebec, Canada, H3A 1A1
Sponsors and Collaborators
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
Investigators
Principal Investigator: Greg Knoll, MD Ottawa Hospital Research Institute
  More Information

No publications provided by Ottawa Hospital Research Institute

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT01353339     History of Changes
Other Study ID Numbers: CIHR MOP 222493, 2010-292
Study First Received: May 11, 2011
Last Updated: July 3, 2013
Health Authority: Canada: Health Canada
Canada: Ethics Review Committee

Keywords provided by Ottawa Hospital Research Institute:
Kidney Transplant
BK Polyomavirus Infection

Additional relevant MeSH terms:
Virus Diseases
Ofloxacin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents, Urinary
Renal Agents

ClinicalTrials.gov processed this record on July 22, 2014