Clinical trial NCT01353339: Quinolone Prophylaxis for the Prevention of BK Virus Infection in Kidney Transplantation: A Pilot Study
Official title: Quinolone Prophylaxis for the Prevention of BK Virus Infection in Kidney Transplantation: A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Disease Due to BK Polyomavirus
Kidney Transplant Infection
Keywords: Kidney Transplant
BK Polyomavirus Infection
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: St. Paul's Hospital, Canada
name: Vancouver General Hospital
name: University of Alberta
name: University of Manitoba
name: University Health Network, Toronto
name: Unity Health Toronto
name: St. Joseph's Healthcare Hamilton
name: London Health Sciences Centre
name: McGill University Health Centre/Research Institute of the McGill University Health Centre
name: Dalhousie University
First posted: 2011-05-13
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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

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 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.

Primary outcomes:
measure: Occurrence of BK Viruria
timeFrame: 12 months post-transplantation
Secondary outcomes:
measure: Adverse Events
timeFrame: 12 months
measure: Acute Rejection
timeFrame: 12 months
measure: Clostridium Difficile Associated Diarrhea
timeFrame: 12 months
measure: Infections
timeFrame: 12 months
measure: Quinolone Resistance
timeFrame: 12 months
measure: Allograft Loss
timeFrame: 12 months
measure: Mortality
timeFrame: 12 months
measure: Adherence
timeFrame: 12 months
measure: Use of Quinolones
timeFrame: 12 months
measure: Proportion of Patient Drop-out and Loss to Follow-up
timeFrame: 12 months
measure: Quantitative BK Urine Viral Load
timeFrame: 12 months
measure: BK Viremia
timeFrame: 12 months
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: Capital Health - University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: Winnipeg Health Science Center
state: Manitoba
city: Halifax
country: Canada
facility: QEII Health Science Center
state: Nova Scotia
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare
state: Ontario
city: London
country: Canada
facility: London Health Science Center
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Center
state: Quebec
Study officials:
affiliation: Ottawa Hospital Research Institute
name: Greg Knoll, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.