Clinical trial NCT03692715: Antibiotic Prophylaxis Before Shock Wave Lithotripsy
Official title: A Multicenter Randomized Controlled Trial Assessing the Efficacy of Antimicrobial Prophylaxis for Extracorporeal Shock Wave Lithotripsy on Reducing Urinary Tract Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Ureteral Stones
Ureteral Calculi
Nephrolithiasis
Keywords: ureteral stones; ureteral calculi; shockwave lithotripsy
Lead sponsor: Clinical Urology and Epidemiology Working Group
Sponsor class: OTHER_GOV
Collaborators: name: University of Helsinki
name: Helsinki University Central Hospital
name: Western University, Canada
name: Centre de recherche du Centre hospitalier universitaire de Sherbrooke
name: King Abdulaziz University
name: Hospital Sao Luiz
name: St. Petersburg State Pavlov Medical University
name: University Hospital, Basel, Switzerland
name: Tallaght University Hospital
name: Tabriz University of Medical Sciences
name: Dr Cipto Mangunkusumo General Hospital
First posted: 2018-10-02
Enrollment: 1732
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: This is a two arm, double blind RCT comparing the use of a single dose ciprofloxacin prior to SWL to saline alone. The multicenter trial will be conducted with a pragmatic emphasis including both high volume and low volume sites internationally.

Detailed description: This is a two arm, double blind randomized controlled trial (RCT) comparing the use of a single dose ciprofloxacin prior to shock wave lithotripsy (SWL) to placebo. The multicenter trial will be conducted with a pragmatic emphasis including both high volume and low volume sites internationally.

Eligibility criteria include patients older than 18 years presenting for SWL who do not meet one of the pre-defined exclusion criteria (outlined below).

Eligible patients will provide written informed consent. Patients will undergo central randomization, which will be accessed by phone or internet. Un-blinding will occur only once statistical analysis is complete.

Patients will undergo SWL using standard procedures at the participating center. Participants will asked to provide a pre-procedure study questionnaire, a modified International Prostate Symptom Score (IPSS) questionnaire and a urine sample for analysis prior to SWL and follow-up. Follow-up questionnaires and a requisition for urine culture will be provided in a pre-stamped, self-addressed envelope along with instructions to return both culture and questionnaires to their participating center at 7-14 days post-SWL. If the follow-up questionnaire has not been received by post-operative day 10 patients will receive a reminder phone call. A second envelope will be sent containing a requisition for urine culture and follow-up questionnaire when necessary.

Alternatively, if a 2 week follow-up is conducted at the participating site then data-forms can be completed and collected at that time. In the event that a urine culture was not submitted 7 days post-operatively, one can be collected up to 14 days post-op. Additional clinical parameters such as presence of double J, stone characteristics and renal insufficiency will be recorded at the time of SWL by the dedicated research staff at the participating center. Data acquisition and occurrence of outcomes will be monitored continuously with scheduled audits.

Primary and secondary outcomes are outlined below.

The power calculation for this protocol was performed using Stata v.10.1 (StataCorp, College Station, TX). The investigators used the American Urological Association Best Practice Statement on antibiotic prophylaxis to estimate a 60% relative risk reduction with treatment arm. Therefore to achieve a power of 90% with a significance level of p\<0.05, 661 patients will need to be recruited in each arm for a total of 1,322 patients. Accounting for 10% loss to follow-up, the total required will be 1454, or approximately 1500 patients. Assuming that 25% of patients screened will either refuse to be randomized or will meet one of the pre-defined exclusion criteria, a minimum of 2000 patients will need to be screened in order to randomize 1500 patients.

Eligibility criteria: Inclusion Criteria:

Patients older than 18 years presenting for SWL who do not meet one of the pre-defined exclusion criteria.

Exclusion Criteria:

* Pre-SWL urine analysis positive for nitrites
* Pre-SWL urine culture reveals \>10e5 Colony Forming Unit/ml of bacteria (positive urine culture)
* Taking antibiotics for Urinary Tract Infection (UTI) or other cause
* Suspected struvite stone (based on previous stone analysis, or partial staghorn)
* Presence of nephrostomy tube
* Requiring cystoscopy and ureteral stent insertion on the day of SWL
* Presence of Foley catheter or patient on regular clean intermittent catheterization (CIC)
* Presence of urinary diversion (ie: ileal conduit)
* History of urosepsis prior to SWL
* Known allergic reaction to trial antibiotic
* Previous randomization in this trial
* In the opinion of the independent treating urologist, it is not in the patient's best interest to participate

Primary outcomes:
measure: Composite outcome including positive urine culture, symptoms of cystitis, pyelonephritis or urosepsis
timeFrame: 7-14 days post-shockwave lithotripsy
Secondary outcomes:
measure: Bacteriuria defined as ≥ 100000 Colony Forming Unit/ml
timeFrame: 7-14 days post-shockwave lithotripsy
measure: Symptoms of cystitis defined as new onset burning sensation or pain with voiding, frequency, urgency
timeFrame: 7-14 days post-shockwave lithotripsy
measure: Pyelonephritis or urosepsis defined as Hospital admission with fever ≥38.5 Celsius
timeFrame: 7-14 days post-shockwave lithotripsy
measure: Change in International Prostate Symptom Score (IPSS) total score (0-35, higher score indicates worse outcome)
timeFrame: 14 days post-shockwave lithotripsy
measure: Individual components of International Prostate Symptom Score (0-7 per domain, with higher score indicating worse outcome)
timeFrame: 14 days post-shockwave lithotripsy
measure: Pain scale determined on a range of 0-5 with higher score indicating worse outcome
timeFrame: 14 days post-shockwave lithotripsy
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Hospital Sao Luiz
city: London
country: Canada
facility: Western University Hospital
state: Ontario
city: Sherbrooke
country: Canada
facility: University of Sherbrooke
state: Quebec
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Jakarta
country: Indonesia
facility: Universitas Indonesia - Cipto Mangunkusumo Hospital
city: Tabriz
country: Iran, Islamic Republic of
facility: Tabriz University of Medical Science
city: Dublin
country: Ireland
facility: Tallaght University Hospital
city: Saint Petersburg
country: Russian Federation
facility: St Petersburg State Pavlov Medical University
city: Jeddah
country: Saudi Arabia
facility: King Abdulaziz University
city: Basel
country: Switzerland
facility: Department of Urology, University Hospital Basel
Study officials:
affiliation: University of Helsinki
name: Kari AO Tikkinen, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: McMaster University
name: Philippe D Violette, MD CM
role: PRINCIPAL_INVESTIGATOR
References: