Ureteral StonesPhase 4APPEALNCT03692715
Antibiotic Prophylaxis Before Shock Wave Lithotripsy
A Phase 4 study testing Ciprofloxacin in people with Ureteral Stones and Ureteral Calculi, run by Clinical Urology and Epidemiology Working Group at 10 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ureteral Stones, Ureteral Calculi, Nephrolithiasis
- What is being tested?
- Ciprofloxacin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,732 participants
- Where
- 10 sitesin 9 countries
- Study dates
- 27 Sep 2018to 31 Dec 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients older than 18 years presenting for SWL who do not meet one of the pre-defined exclusion criteria.
Who cannot join
- 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
Show all 12Show fewer
- 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 locations and contacts
10 sites in 9 countries.
10 sites in 9 countries
Canada2 sites
Western University Hospital
London, Ontario, N6C 2V5
University of Sherbrooke
Sherbrooke, Quebec, J1H 5H3
About this study
Official title: 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.
Read the 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.
- Conditions
- Ureteral Stones, Ureteral Calculi, Nephrolithiasis
- Being tested
- Ciprofloxacin, Placebo
- Keywords
- ureteral stones; ureteral calculi; shockwave lithotripsy
- Medical subject headings
- Ureteral Calculi, Nephrolithiasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CiprofloxacinDrug
Also called Cipro
Oral or intravenous ciprofloxacin prior to shockwave lithotripsy.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| ciprofloxacin | Experimental | Single dose oral or intravenous ciprofloxacin prior to shockwave lithotripsy Receives: Drug: Ciprofloxacin |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite outcome including positive urine culture, symptoms of cystitis, pyelonephritis or urosepsis
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.
Measured: 7-14 days post-shockwave lithotripsy
Secondary outcomes (6)
Bacteriuria defined as ≥ 100000 Colony Forming Unit/ml
Bacteriuria will be assessed as a dichotomous variable with presence of is ≥100000 Colony Forming Unit/ml will be considered as an event
Measured: 7-14 days post-shockwave lithotripsy
Symptoms of cystitis defined as new onset burning sensation or pain with voiding, frequency, urgency
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
Measured: 7-14 days post-shockwave lithotripsy
Pyelonephritis or urosepsis defined as Hospital admission with fever ≥38.5 Celsius
Pyelonephritis or urosepsis will be assessed as a dichotomous variable with Hospital admission with fever ≥38.5 Celsius will be considered as an event
Measured: 7-14 days post-shockwave lithotripsy
Change in International Prostate Symptom Score (IPSS) total score (0-35, higher score indicates worse outcome)
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
Measured: 14 days post-shockwave lithotripsy
Individual components of International Prostate Symptom Score (0-7 per domain, with higher score indicating worse outcome)
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
Measured: 14 days post-shockwave lithotripsy
Pain scale determined on a range of 0-5 with higher score indicating worse outcome
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
Measured: 14 days post-shockwave lithotripsy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2018
- Study start27 Sep 2018
- Primary completion31 Dec 2024
- Study completion31 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ureteral StonesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,732 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clinical Urology and Epidemiology Working Group
- Sponsor type
- Other government
- Collaborators
- University of Helsinki, Helsinki University Central Hospital, Western University, Canada, Centre de recherche du Centre hospitalier universitaire de Sherbrooke, King Abdulaziz University, Hospital Sao Luiz, St. Petersburg State Pavlov Medical University, University Hospital, Basel, Switzerland, Tallaght University Hospital, Tabriz University of Medical Sciences, Dr Cipto Mangunkusumo General Hospital
- Responsible party
- Principal investigator, Kari Tikkinen, Clinical Urology and Epidemiology Working Group
- Investigators
- Kari AO Tikkinen, MD PhD, Principal investigator, University of HelsinkiPhilippe D Violette, MD CM, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03692715
- Sponsor's protocol ID
- CLUE
- Acronym
- APPEAL
- Status last verified
- Mar 2025
- First submitted
- 21 Aug 2018
- Last updated
- 28 Mar 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Randomized Controlled Trial Assessing the Efficacy of Antimicrobial Prophylaxis for Extracorporeal Shock Wave Lithotripsy on Reducing Urinary Tract Infection
- ClinicalTrials.gov ID
- NCT03692715
- Acronym / sponsor ID
- APPEAL / CLUE
- Conditions
- Ureteral Stones, Ureteral Calculi, Nephrolithiasis
- Keywords
- ureteral stones; ureteral calculi; shockwave lithotripsy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,732 participants (actual)
- Lead sponsor
- Clinical Urology and Epidemiology Working GroupOther government
- Collaborators
- University of Helsinki, Helsinki University Central Hospital, Western University, Canada, Centre de recherche du Centre hospitalier universitaire de Sherbrooke, King Abdulaziz University, Hospital Sao Luiz, St. Petersburg State Pavlov Medical University, University Hospital, Basel, Switzerland, Tallaght University Hospital, Tabriz University of Medical Sciences, Dr Cipto Mangunkusumo General Hospital
- Study start
- 27 Sep 2018 (actual)
- Primary completion
- 31 Dec 2024 (actual)
- Study completion
- 31 Dec 2024 (actual)
- First posted
- 2 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ciprofloxacin | Experimental | Drug: CiprofloxacinSingle dose oral or intravenous ciprofloxacin prior to shockwave lithotripsy |
| Placebo | Placebo comparator | Drug: Placeboidentical oral placebo if oral cipro was used, or intravenous saline alone in a blinded fashion if IV cipro was used prior to shockwave lithotripsy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients older than 18 years presenting for SWL who do not meet one of the pre-defined exclusion criteria.
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CiprofloxacinAlso: CiproOral or intravenous ciprofloxacin prior to shockwave lithotripsy. | Drug | ciprofloxacin |
| Placeboidentical 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 |
Primary outcome
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.
6 secondary outcomes
Bacteriuria defined as ≥ 100000 Colony Forming Unit/ml
Time frame: 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
Pyelonephritis or urosepsis defined as Hospital admission with fever ≥38.5 Celsius
Time frame: 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
Individual components of International Prostate Symptom Score (0-7 per domain, with higher score indicating worse outcome)
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kari AO Tikkinen, MD PhD principal investigator
University of Helsinki
Philippe D Violette, MD CM principal investigator
McMaster University
10 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ciprofloxacin in people with Ureteral Stones and Ureteral Calculi, run by Clinical Urology and Epidemiology Working Group at 10 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Canada, Brazil, Finland, Indonesia, Iran and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite outcome including positive urine culture, symptoms of cystitis, pyelonephritis or urosepsis (time frame: 7-14 days post-shockwave lithotripsy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2025.