Evaluation of Safety and Tolerability of Nitric Oxide Impregnated Urinary Catheters

Study Overview
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Brief Summary
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According to the World Health Organization, hundreds of millions of patients are affected by health-care associated infections worldwide each year, resulting in prolonged hospital stays, long-term disabilities, deaths, and financial losses for health systems. The most common hospital-acquired infection is Urinary Tract Infection (UTI), accounting for almost 40% of all nosocomial infections. Most hospital-acquired UTIs are associated with catheterization. In fact, urinary catheter-related bacteriuria is the most common health care associated infection worldwide. Catheter-associated UTI (CAUTI) develops following adhesion of planktonic bacteria to the surface of the catheter and colonization, creating a persistent environment called a biofilm. The nature of biofilm structure together with the physiological attributes of biofilm organisms confers an inherent resistance to various antimicrobial agents such as antibiotics, disinfectants or germicides, augmenting the potential of these pathogens to cause infections in catheterized patients. Nitric oxide (NO) is a naturally-produced gas molecule with broad-spectrum antimicrobial activity. NO is used in the clinics to treat pulmonary hypertension in neonates and adults. Studies have shown that low-dose NO is associated with prevention of biofilm formation, biofilm dispersal and elimination of bacteria. It is suggested that NO prevents bacteria attachment to catheter surfaces and inhibits biofilm formation in a mechanism involving reduction and modification of proteins that mediate cell-substrate and cell-cell interactions. The investigators team, using a proprietary technology impregnate urinary catheters with NO (i.e. NO-impregnated catheters). These catheters release low concentration of NO following exposure to urine over a 14-day period. In vitro studies showed that NO-impregnated catheters prevent bacterial colonization and biofilm formation of Escherichia coli on exterior and luminal surfaces of the catheters. In addition, NO released from these catheters is able to eradicate up to 4log colony forming unit/ml of bacteria within the surrounding media. Moreover, NO-impregnated catheters exhibit superior performance compared to silver-coated catheters, and similar anti-infective properties compared to antibiotic-coated catheters. Primary objectives: To assess the safety and tolerability of NO-impregnated catheters in patients older than 18 years old undergoing radical prostatectomy and catheterized for 7-14 days.

Official Title
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Prospective, Phase I, Single-Center, Evaluation of the Safety and Tolerability of Nitric Oxide Impregnated Urinary Catheters in Patients Undergoing Radical Prostatectomy

Conditions
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Urinary Tract Infection, Bacteriuria

Intervention / Treatment
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* Device: Nitric Oxide impregnated catheter


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients before radical prostatectomy at the Department of Urology in Beilinson Medical Center, which will be catheterized for 7-14 days. Age: ≥ 18 years. Patients with a life expectancy of more than 12 months. The investigator has completed a medical history and a physical examination to assure that the patients meets all study enrollment criteria. The patient is willing and able to read, understand and sign the study specific informed consent form. Exclusion Criteria: A urinary culture demonstrating UTI before surgery. A patient with an indwelling urinary catheter prior to surgery. Expected life expectancy of less than 12 months. Concurrent illness, disability or geographical residence that would hamper study participation. Patients with underlying diseases such as heart disease, lung disease, skin disease or infection involving the penis, scrotum and groin, immunocompromised patients (transplant recipients, HIV carriers) or any other disease or condition that according to the physician opinion will influence the study results. Patients with known urethral stricture. Patients with recurrent UTIs. Current participation in another clinical investigation of a medical device or a drug or has participated in such a study within 30 days prior to study enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nitric oxide impregnated catheter<br> | Device: Nitric Oxide impregnated catheter<br>* Patients undergoing radical prostatectomy will be catheterized for 7-14 days with Nitric Oxide impregnated Foley catheters<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events associated with Nitric Oxide impregnated catheters |  | 30-45 days | 
| Proportion of patients (%) who prematurely discontinued the study due to adverse events or severe adverse events associated with Nitric oxide impregnated catheters |  | 30-45 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measuring biofilm forming bacteria on the surface of Nitric Oxide impregnated and non impregnated Foley catheters after indwelling for 7 to 14 days |  | 7-14 days | 
| Measuring bacteriuria (by urine culture) for Nitric Oxide impregnated and non impregnated Foley catheters prior to insertion, 1 day after insertion, every day during hospitalization, on catheter removal day, and 30 days after catheterization |  | 30-45 days | 
| Measuring number of urinary tract infection (UTI) events following catheterization with Nitric Oxide impregnated and non impregnated Foley catheters |  | 30-45 days | 
| Proportion of patients (%) who prematurely discontinued the study for any reason |  | 30-45 days |