Retrospective Analysis of Ialuril vs. Standard of Care in Recurrent Urinary Tract Infections (RAISC-RUTI)

INTRAVESICAL ADMINISTRATION OF COMBINED HYALURONIC ACID (HA) AND CHONDROITIN SULPHATE (CS) vs. STANDARD OF CARE FOR THE TREATMENT OF RECURRENT URINARY TRACT INFECTIONS (RUTIs)

The purpose of this study is to assess the effectiveness and costs associated with the intravesical administration of combined hyaluronic acid (HA) and chondroitin sulphate (CS) compared to the current standard management of recurrent urinary tract infections in adult women diagnosed with recurrent urinary tract infections (RUTI).

Study Overview

• Status: Unknown
• Conditions: Recurrent Urinary Tract Infections
• Intervention / Treatment: Device: Ialuril

Detailed Description

RUTI is defined as at least three episodes of uncomplicated urinary tract infections accompanied by clinical symptoms and documented by urine culture with the isolation of >103 colony forming units (CFU)/ml of an identified pathogen in the last year (M. Grabe, T.E. Bjerklund-Johansen, H. Botto, B. Wullt, M. Çek, K.G. Naber, R.S. Pickard, P. Tenke, F. Wagenlehner. Guidelines on Urological Infections. European Association of Urology 2012).

In order to do so, we will perform a retrospective analysis on prospectively collected patient data in nine European centres.

The treatment schedule for the intravesical administration of combined hyaluronic acid (HA) 1.6% and chondroitin sulphate (CS) 2.0% is one instillation per week for the first month, followed by one instillation every two weeks for the second month and one instillation per month until stable remission of the symptoms.

The current standard management of RUTI in Europe is represented by the antimicrobial prophylaxis (continuous or postcoital), as described in the Guidelines on Urological Infections of the European Association of Urology or Immunoactive prophylaxis or Prophylaxis with probiotics or Prophylaxis with cranberry, or combination of these.

We will collect patient characteristics as age, BMI, sexual activity, employment status, severity of the disease, comorbidities.

Our primary clinical outcome will be the occurrence of objective (bacteriologically confirmed) recurrence within 12 months after the start of the treatment. Other outcomes will be the occurrence of clinical or symptoms based recurrence; the time to objective or symptoms based recurrence, evaluated from the start of the treatment until the first occurrence of an objective or symptoms based urinary tract infection, and the overall number of objective or symptoms based urinary tract infections experienced within 12 months after treatment initiation for RUTI.

Information about health related quality of life at baseline and 12 months will be recorded if available.

In terms of resource utilization, we will record the number of medical visits, number and types of laboratory, imaging and instrumental exams, hospitalization, consumption of pharmaceuticals or instrumental therapies (other than intervention and comparator) used within 12 months since treatment initiation. Number of days absent from work due to RUTI will be recorded when available. Costs will be attributed according to the perspective of the National Healthcare System searching for relevant data sources in each country.

Standard descriptive statistics, such as mean, median, range, and proportions, will be used to summarize patient characteristics and other collected variables. The Chi-Square test will be used to compare differences in proportions and the Mann-Whitney U test to compare continuous variables, with or without logarithmic transformation. The Kaplan-Meier method will be used to estimate time to recurrence outcomes.

• Study Type: Observational
• Enrollment (Anticipated): 500

Contacts and Locations

Study Locations

• Italy
  • Perugia, Italy, 06156
    • Recruiting
    • Ospedale S. Maria Della Misericordia
    • Contact: Massimo Lazzeri, PhD; Phone Number: +393391072211; Email: lazzeri.maximus@gmail.com
    • Principal Investigator: Elisabetta Costantini, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

The study will consider women with recurrent urinary tract infections who started their treatments at the Urology Departments at the enrolling centres.

Description

Inclusion Criteria:

• Women aged 18-75 years old.
• Women diagnosed with recurrent urinary tract infections, defined as at least three episodes of uncomplicated urinary tract infections accompanied by clinical symptoms and documented by urine culture with the isolation of >103 CFU/ml of an identified pathogen in the last year. Uncomplicated or 'simple' UTI is defined as an infection in a person with normal urinary tract and function.

Exclusion criteria:

- Women with complicated urinary tract infections. Complicated urinary tract infection occurs in individuals with functional or structural abnormalities of the genitourinary tract.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ialuril; Intravesical administration of combined hyaluronic acid (HA) 1.6% and chondroitin sulphate (CS) 2.0% once per week for the first month, followed by one instillation every two weeks for the second month and one instillation per month until stable remission of the symptoms.	Device: Ialuril; The treatment is an intravesical administration of combined hyaluronic acid (HA) 1.6% and chondroitin sulphate (CS) 2.0% once per week for the first month, followed by one instillation every two weeks for the second month and one instillation per month until stable remission of the symptoms.
Standard of care; Antimicrobial prophylaxis (continuous or postcoital), as described in the Guidelines on Urological Infections of the European Association of Urology or Immunoactive prophylaxis or Prophylaxis with probiotics or Prophylaxis with cranberry, or combination of these.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Urinary tract infection recurrence	At least one bacteriologically confirmed urinary tract infection experienced within 12 months after the treatment initiation.	within 12 months after treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of symptomatic urinary tract infection recurrence	At least one symptoms based urinary tract infection experienced within 12 months after the treatment initiation.	within 12 months after treatment initiation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean direct overall costs	Mean overall costs, expressed in euros, comprehensive of costs of each treatment options and other direct medical costs (i.e. visits, additional medical therapies required because of recurrences or adverse events, hospitalization) measured over 12 months after treatment initiation for each cohort of patients.	within 12 months after treatment initiation
Number of days absent from work	Number of days of absence from work due to the recurrent urinary tract infections within 12 months since the start of the treatment.	within 12 months after treatment initiation
Time-to-recurrence	Time from the start of the treatment until the first occurrence of an objective or symptoms based urinary tract infection	12 months after treatment initiation

Collaborators and Investigators

• Sponsor: Study Group for Urogenital Diseases, Italy
• Investigators: Principal Investigator: Massimo Lazzeri, PhD, Università Vita-Salute San Raffaele

Publications and helpful links

General Publications

• Naber KG, Bergman B, Bishop MC, Bjerklund-Johansen TE, Botto H, Lobel B, Jinenez Cruz F, Selvaggi FP; Urinary Tract Infection (UTI) Working Group of the Health Care Office (HCO) of the European Association of Urology (EAU). EAU guidelines for the management of urinary and male genital tract infections. Urinary Tract Infection (UTI) Working Group of the Health Care Office (HCO) of the European Association of Urology (EAU). Eur Urol. 2001 Nov;40(5):576-88. doi: 10.1159/000049840.
• Ciani O, Arendsen E, Romancik M, Lunik R, Costantini E, Di Biase M, Morgia G, Fragala E, Roman T, Bernat M, Guazzoni G, Tarricone R, Lazzeri M. Intravesical administration of combined hyaluronic acid (HA) and chondroitin sulfate (CS) for the treatment of female recurrent urinary tract infections: a European multicentre nested case-control study. BMJ Open. 2016 Mar 31;6(3):e009669. doi: 10.1136/bmjopen-2015-009669.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Anticipated): March 1, 2014
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: October 7, 2013
• First Submitted That Met QC Criteria: December 14, 2013
• First Posted (Estimate): December 19, 2013

Study Record Updates

• Last Update Posted (Estimate): February 12, 2014
• Last Update Submitted That Met QC Criteria: February 11, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: RUTI
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Infections; Communicable Diseases; Recurrence; Urinary Tract Infections
• Other Study ID Numbers: RAISC-RUTI