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

Kidney Transplant Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01353339
• Other study ID #: CIHR MOP 222493, 2010-292
• Status: Completed
• Phase: Phase 4
• Start date: December 1, 2011
• Est. completion date: February 25, 2014

Study information

• Verified date: October 2014
• Source: Ottawa Hospital Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 154
• Est. completion date: February 25, 2014
• Est. primary completion date: February 25, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Disease Due to BK Polyomavirus
• Infections
• Kidney Transplant Infection
• Virus Diseases

Intervention

Drug:
• Levofloxacin
500mg, PO, once daily for 3 months

Locations

Country	Name	City	State
Canada	Capital Health - University of Alberta Hospital	Edmonton	Alberta
Canada	QEII Health Science Center	Halifax	Nova Scotia
Canada	St. Joseph's Healthcare	Hamilton	Ontario
Canada	London Health Science Center	London	Ontario
Canada	McGill University Health Center	Montreal	Quebec
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	University Health Network	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Columbia
Canada	Vancouver General Hospital	Vancouver	British Columbia
Canada	Winnipeg Health Science Center	Winnipeg	Manitoba

Sponsors (12)

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

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of BK Viruria	BK viruria was defined as 500 copies/mL or more of BK virus DNA in the urine.	12 months post-transplantation
Secondary	Adverse Events	Incidence and type of all adverse events	12 months
Secondary	Acute Rejection	Incidence of Acute rejection	12 months
Secondary	Clostridium Difficile Associated Diarrhea	Incidence of microbiologically confirmed clostridium difficile associated diarrhea	12 months
Secondary	Infections	Incidence of other infections (viral, bacterial and fungal) based on established guidelines	12 months
Secondary	Quinolone Resistance	Incidence of quinolone resistance where a quinolone would have been a therapeutic option	12 months
Secondary	Allograft Loss	Absence of kidney function in allograft	12 months
Secondary	Mortality		12 months
Secondary	Adherence	Proportion of randomized participants who are adherent to the protocol.	12 months
Secondary	Use of Quinolones	Use of quinolones outside of the protocol	12 months
Secondary	Proportion of Patient Drop-out and Loss to Follow-up		12 months
Secondary	Quantitative BK Urine Viral Load		12 months
Secondary	BK Viremia	BK viremia defined as =250 copies/mL of BK virus DNA in the plasma	12 months