Antibiotic Prophylaxis Before Shock Wave Lithotripsy (APPEAL)

Clinical Urology and Epidemiology Working Group

Status and phase: Completed; Phase 4

Conditions: Ureteral Calculi; Ureteral Stones; Nephrolithiasis

Treatments: Drug: Placebo; Drug: Ciprofloxacin

Study type: Interventional

Funder types: Other

Identifiers

NCT03692715

CLUE

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,732 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,732 participants in 2 patient groups, including a placebo group

ciprofloxacin

Experimental group

Description:

Single dose oral or intravenous ciprofloxacin prior to shockwave lithotripsy

Treatment:

Drug: Ciprofloxacin

Placebo

Placebo Comparator group

Description:

identical oral placebo if oral cipro was used, or intravenous saline alone in a blinded fashion if IV cipro was used prior to shockwave lithotripsy.

Treatment:

Drug: Placebo