Antibiotic Prophylaxis Before Shock Wave Lithotripsy (APPEAL)

October 8, 2021 updated by: Kari Tikkinen, Clinical Urology and Epidemiology Working Group

A Multicenter Randomized Controlled Trial Assessing the Efficacy of Antimicrobial Prophylaxis for Extracorporeal Shock Wave Lithotripsy on Reducing Urinary Tract Infection

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

1500

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: ciprofloxacin
Single dose oral or intravenous ciprofloxacin prior to shockwave lithotripsy
Drug: Ciprofloxacin
Oral or intravenous ciprofloxacin prior to shockwave lithotripsy.
Other Names:
  • Cipro
PLACEBO_COMPARATOR: Placebo
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.
Drug: Placebo
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite outcome including positive urine culture, symptoms of cystitis, pyelonephritis or urosepsis
Time Frame: 7-14 days post-shockwave lithotripsy
The composite outcome with be assessed as a dichotomous variable. The presence of Positive post-SWL urine culture (≥ 10e5 Colony Forming Unit/ ml), with either one or more of symptoms of cystitis (defined as new onset burning sensation or pain with voiding, frequency, urgency), or pyelonephritis or urosepsis (hospital admission with fever ≥38.5 C) will be considered as an event.
7-14 days post-shockwave lithotripsy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bacteriuria defined as ≥ 100000 Colony Forming Unit/ml
Time Frame: 7-14 days post-shockwave lithotripsy
Bacteriuria will be assessed as a dichotomous variable with presence of is ≥100000 Colony Forming Unit/ml will be considered as an event
7-14 days post-shockwave lithotripsy
Symptoms of cystitis defined as new onset burning sensation or pain with voiding, frequency, urgency
Time Frame: 7-14 days post-shockwave lithotripsy
Symptoms of cystitis will be considered as a dichotomous variable with new onset burning sensation or pain with voiding, frequency, urgency will be considered an event
7-14 days post-shockwave lithotripsy
Pyelonephritis or urosepsis defined as Hospital admission with fever ≥38.5 Celsius
Time Frame: 7-14 days post-shockwave lithotripsy
Pyelonephritis or urosepsis will be assessed as a dichotomous variable with Hospital admission with fever ≥38.5 Celsius will be considered as an event
7-14 days post-shockwave lithotripsy
Change in International Prostate Symptom Score (IPSS) total score (0-35, higher score indicates worse outcome)
Time Frame: 14 days post-shockwave lithotripsy
Change in total value of IPSS score will be assessed as a continuous variable with a range from 0-35 with higher scores indicating more severe symptoms. This score is calculated by summation of individual component scores (0-5) across 7 domains
14 days post-shockwave lithotripsy
Individual components of International Prostate Symptom Score (0-7 per domain, with higher score indicating worse outcome)
Time Frame: 14 days post-shockwave lithotripsy
Individual IPSS domains will be assessed as continuous variables and include incomplete emptying, frequency, intermittency, urgency, weak stream, straining and nocturia. Higher scores as considered as more severe symptoms
14 days post-shockwave lithotripsy
Pain scale determined on a range of 0-5 with higher score indicating worse outcome
Time Frame: 14 days post-shockwave lithotripsy
Pain scale will be assessed as a continuous variable. The scale will be elicited by asking In the past week, how often have you had burning or discomfort with urination? Higher score is considered as more severe symptoms
14 days post-shockwave lithotripsy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Clinical Urology and Epidemiology Working Group

Collaborators

Helsinki University Central Hospital
Centre de recherche du Centre hospitalier universitaire de Sherbrooke
University Hospital, Basel, Switzerland
University of Western Ontario, Canada
University of Helsinki
King Abdulaziz University
St. Petersburg State Pavlov Medical University
Dr Cipto Mangunkusumo General Hospital
Tabriz University of Medical Sciences
Tallaght University Hospital
Hospital Sao Luiz

Investigators

  • Principal Investigator: Kari AO Tikkinen, MD PhD, University of Helsinki
  • Principal Investigator: Philippe D Violette, MD CM, McMaster University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 27, 2018

Primary Completion (ANTICIPATED)

December 31, 2024

Study Completion (ANTICIPATED)

December 31, 2024

Study Registration Dates

First Submitted

August 21, 2018

First Submitted That Met QC Criteria

September 30, 2018

First Posted (ACTUAL)

October 2, 2018

Study Record Updates

Last Update Posted (ACTUAL)

October 18, 2021

Last Update Submitted That Met QC Criteria

October 8, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLUE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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