Evaluation of Safety and Tolerability of Nitric Oxide Impregnated Urinary Catheters

• ClinicalTrials.gov Identifier: NCT02277171
• Recruitment Status: Completed
• First Posted: October 28, 2014
• Last Update Posted: December 24, 2015
• Sponsor: Enox Israel Ltd
• Collaborator: Rabin Medical Center
• Information provided by (Responsible Party): Enox Israel Ltd

Tracking Information

• First Submitted Date: October 19, 2014
• First Posted Date: October 28, 2014
• Last Update Posted Date: December 24, 2015
• Study Start Date: December 2014
• Actual Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 26, 2014)

• Number of participants with adverse events associated with Nitric Oxide impregnated catheters [ Time Frame: 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 [ Time Frame: 30-45 days ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 26, 2014)

• Measuring biofilm forming bacteria on the surface of Nitric Oxide impregnated and non impregnated Foley catheters after indwelling for 7 to 14 days [ Time Frame: 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 [ Time Frame: 30-45 days ]
• Measuring number of urinary tract infection (UTI) events following catheterization with Nitric Oxide impregnated and non impregnated Foley catheters [ Time Frame: 30-45 days ]
• Proportion of patients (%) who prematurely discontinued the study for any reason [ Time Frame: 30-45 days ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Prevention

Condition

• Urinary Tract Infection
• Bacteriuria

Intervention

Device: Nitric Oxide impregnated catheter

Patients undergoing radical prostatectomy will be catheterized for 7-14 days with Nitric Oxide impregnated Foley catheters

Study Arms

Experimental: Nitric oxide impregnated catheter

Intervention: Device: Nitric Oxide impregnated catheter

Publications *

• Regev-Shoshani G, Ko M, Miller C, Av-Gay Y. Slow release of nitric oxide from charged catheters and its effect on biofilm formation by Escherichia coli. Antimicrob Agents Chemother. 2010 Jan;54(1):273-9. doi: 10.1128/AAC.00511-09. Epub 2009 Nov 2.
• Regev-Shoshani G, Ko M, Crowe A, Av-Gay Y. Comparative efficacy of commercially available and emerging antimicrobial urinary catheters against bacteriuria caused by E. coli in vitro. Urology. 2011 Aug;78(2):334-9. doi: 10.1016/j.urology.2011.02.063.
• Barraud N, Storey MV, Moore ZP, Webb JS, Rice SA, Kjelleberg S. Nitric oxide-mediated dispersal in single- and multi-species biofilms of clinically and industrially relevant microorganisms. Microb Biotechnol. 2009 May;2(3):370-8. doi: 10.1111/j.1751-7915.2009.00098.x. Epub 2009 Mar 13.
• Charville GW, Hetrick EM, Geer CB, Schoenfisch MH. Reduced bacterial adhesion to fibrinogen-coated substrates via nitric oxide release. Biomaterials. 2008 Oct;29(30):4039-44. doi: 10.1016/j.biomaterials.2008.07.005. Epub 2008 Jul 26.
• Ramritu P, Halton K, Collignon P, Cook D, Fraenkel D, Battistutta D, Whitby M, Graves N. A systematic review comparing the relative effectiveness of antimicrobial-coated catheters in intensive care units. Am J Infect Control. 2008 Mar;36(2):104-17. doi: 10.1016/j.ajic.2007.02.012.
• Siddiq DM, Darouiche RO. New strategies to prevent catheter-associated urinary tract infections. Nat Rev Urol. 2012 Apr 17;9(6):305-14. doi: 10.1038/nrurol.2012.68. Review.
• Parida S, Mishra SK. Urinary tract infections in the critical care unit: A brief review. Indian J Crit Care Med. 2013 Nov;17(6):370-4. doi: 10.4103/0972-5229.123451. Review.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 23, 2015): 15
• Original Estimated Enrollment (submitted: October 26, 2014): 12
• Actual Study Completion Date: September 2015
• Actual Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Patients before radical prostatectomy at the Department of Urology in Beilinson Medical Center, which will be catheterized for 7-14 days.
2. Age: ≥ 18 years.
3. Patients with a life expectancy of more than 12 months.
4. The investigator has completed a medical history and a physical examination to assure that the patients meets all study enrollment criteria.
5. The patient is willing and able to read, understand and sign the study specific informed consent form.

Exclusion Criteria:

1. A urinary culture demonstrating UTI before surgery.
2. A patient with an indwelling urinary catheter prior to surgery.
3. Expected life expectancy of less than 12 months.
4. Concurrent illness, disability or geographical residence that would hamper study participation.
5. 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.
6. Patients with known urethral stricture.
7. Patients with recurrent UTIs.
8. 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT02277171
• Other Study ID Numbers: ENOX PHASE I_1.1
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Enox Israel Ltd
• Study Sponsor: Enox Israel Ltd
• Collaborators: Rabin Medical Center

Investigators

• Study Chair: David Greenberg, prof.; ENOX

• PRS Account: Enox Israel Ltd
• Verification Date: December 2015