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

Sponsor

Ottawa Hospital Research Institute (Other)

Overall Status

Completed

CT.gov ID

NCT01353339

Collaborator

Canadian Institutes of Health Research (CIHR) (Other), St. Paul's Hospital, Canada (Other), Vancouver General Hospital (Other), University of Alberta (Other), University of Manitoba (Other), University Health Network, Toronto (Other), Unity Health Toronto (Other), St. Joseph's Healthcare Hamilton (Other), London Health Sciences Centre (Other), McGill University Health Centre/Research Institute of the McGill University Health Centre (Other), Dalhousie University (Other)

154

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary Research Questions:

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

Under efficacy, this pilot will determine whether levofloxacin can decrease the incidence of BK viruria and peak urine BK viral load.
Under safety, this pilot will determine the incidence of adverse events with levofloxacin.
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 or Disease	Intervention/Treatment	Phase
Disease Due to BK Polyomavirus Kidney Transplant Infection	Drug: Levofloxacin	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

154 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

Nov 1, 2011

Actual Primary Completion Date :

Apr 1, 2014

Actual Study Completion Date :

Oct 1, 2014

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Efficacy: The time to occurence of BK viruria [12 months post-transplantation]
BK viruria will be defined as ≥1000 copies/mL ok BK virus DNA in the urine.

Secondary Outcome Measures

Adverse Events [12 months]
Incidence and type of all adverse events
Acute rejection [12 months]
Incidence of Acute rejection
Clostridium difficile associated diarrhea [12 months]
Incidence of microbiologically confirmed clostridium difficile associated diarrhea
Infections [12 months]
Incidence of other infections (viral, bacterial and fungal) based on established guidelines
Quinolone resistance [12 months]
Incidence of quinolone resistance where a quinolone would have been a therapeutic option
Effect of levofloxacin on immunosuppressive drug doses and blood levels [12 months]
Transplant failure [12 months]
Mortality [12 months]
Number of patients transplanted [12 months]
Number of patients transplanted during the 8 month recruitment period who are randomized into the trial
Adherence [12 months]
Proportion of randomized participants who are adherent to the protocol.
Use of quinolones [12 months]
Use of quinolones outside of the protocol
Proportion of patient drop-out and loss to follow-up [12 months]
Quantitative BK urine viral load [12 months]
BK viremia [12 months]
Time to occurence of BK viremia, defined as ≥250 copies/mL of BK virus DNA in the plasma

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Capital Health - University of Alberta Hospital	Edmonton	Alberta	Canada	T6G 2B7
2	Vancouver General Hospital	Vancouver	British Columbia	Canada	V5Z 1M9
3	St. Paul's Hospital	Vancouver	British Columbia	Canada	V6Z 1Y6
4	Winnipeg Health Science Center	Winnipeg	Manitoba	Canada
5	QEII Health Science Center	Halifax	Nova Scotia	Canada
6	St. Joseph's Healthcare	Hamilton	Ontario	Canada	L8N 4A6
7	London Health Science Center	London	Ontario	Canada	N6A 5A5
8	The Ottawa Hospital	Ottawa	Ontario	Canada	K1H 8L6
9	University Health Network	Toronto	Ontario	Canada	M5G 2N2
10	St. Michael's Hospital	Toronto	Ontario	Canada
11	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
Unity Health Toronto
St. Joseph's Healthcare Hamilton
London Health Sciences Centre
McGill University Health Centre/Research Institute of the McGill University Health Centre
Dalhousie University