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

Phase 4

Completed

Conditions: Disease Due to BK Polyomavirus
Kidney Transplant Infection

Interventions: Drug: Levofloxacin

Registration Number: NCT01353339

Lead Sponsor: Ottawa Hospital Research Institute

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 154

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
sugar pill	Levofloxacin	-
levofloxacin	Levofloxacin	-

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (11): Capital Health - University of Alberta Hospital
🇨🇦
Edmonton, Alberta, Canada
Winnipeg Health Science Center
🇨🇦
Winnipeg, Manitoba, Canada
Vancouver General Hospital
🇨🇦
Vancouver, British Columbia, Canada
The Ottawa Hospital
🇨🇦
Ottawa, Ontario, Canada
St. Michael's Hospital
🇨🇦
Toronto, Ontario, Canada
University Health Network
🇨🇦
Toronto, Ontario, Canada
St. Joseph's Healthcare
🇨🇦
Hamilton, Ontario, Canada
QEII Health Science Center
🇨🇦
Halifax, Nova Scotia, Canada
St. Paul's Hospital
🇨🇦
Vancouver, British Columbia, Canada
McGill University Health Center
🇨🇦
Montreal, Quebec, Canada
London Health Science Center
🇨🇦
London, Ontario, Canada