Urinary Tract InfectionPhase 1NCT02277171
Evaluation of Safety and Tolerability of Nitric Oxide Impregnated Urinary Catheters
A Phase 1 study testing Nitric Oxide impregnated catheter in people with Urinary Tract Infection and Bacteriuria, run by Enox Israel Ltd.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Urinary Tract Infection, Bacteriuria
- What is being tested?
- Nitric Oxide impregnated catheter
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- No sites listed yet
- Study dates
- Dec 2014to Sep 2015
- Phase
- Phase 1
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
About this study
Official title: Prospective, Phase I, Single-Center, Evaluation of the Safety and Tolerability of Nitric Oxide Impregnated Urinary Catheters in Patients Undergoing Radical Prostatectomy
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.
Read more
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.
- Conditions
- Urinary Tract Infection, Bacteriuria
- Being tested
- Nitric Oxide impregnated catheter
- Medical subject headings
- Urinary Tract Infections, Bacteriuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitric Oxide impregnated catheterDevice
Patients undergoing radical prostatectomy will be catheterized for 7-14 days with Nitric Oxide impregnated Foley catheters
| Study group | Role | What they receive |
|---|---|---|
| Nitric oxide impregnated catheter | Experimental | Not described Receives: Device: Nitric Oxide impregnated catheter |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events associated with Nitric Oxide impregnated catheters
Measured: 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
Measured: 30-45 days
Secondary outcomes (4)
Measuring biofilm forming bacteria on the surface of Nitric Oxide impregnated and non impregnated Foley catheters after indwelling for 7 to 14 days
Measured: 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
Measured: 30-45 days
Measuring number of urinary tract infection (UTI) events following catheterization with Nitric Oxide impregnated and non impregnated Foley catheters
Measured: 30-45 days
Proportion of patients (%) who prematurely discontinued the study for any reason
Measured: 30-45 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2014 (estimated)
- Study startDec 2014
- Primary completionJun 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Urinary Tract InfectionStudies 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 1
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Enox Israel Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Rabin Medical Center
- Responsible party
- Sponsor
- Investigators
- David Greenberg, prof., Study chair, ENOX
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02277171
- Sponsor's protocol ID
- ENOX PHASE I_1.1
- Status last verified
- Dec 2015
- First submitted
- 19 Oct 2014
- Last updated
- 24 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
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.
PubMed 19884372Regev-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.
PubMed 21820571Barraud 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.
PubMed 21261931Charville 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.
PubMed 18657857Ramritu 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.
PubMed 18313512Siddiq 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.
PubMed 22508462Parida 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.
PubMed 24501490
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Phase I, Single-Center, Evaluation of the Safety and Tolerability of Nitric Oxide Impregnated Urinary Catheters in Patients Undergoing Radical Prostatectomy
- ClinicalTrials.gov ID
- NCT02277171
- Acronym / sponsor ID
- ENOX PHASE I_1.1
- Conditions
- Urinary Tract Infection, Bacteriuria
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Enox Israel LtdIndustry (pharma, biotech, devices)
- Collaborators
- Rabin Medical Center
- Study start
- Dec 2014
- Primary completion
- Jun 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 28 Oct 2014 (estimated)
- 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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nitric oxide impregnated catheter | Experimental | Device: Nitric Oxide impregnated catheter |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
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 |
|---|---|---|
| Nitric Oxide impregnated catheterPatients undergoing radical prostatectomy will be catheterized for 7-14 days with Nitric Oxide impregnated Foley catheters | Device | Nitric oxide impregnated catheter |
Primary outcome
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
4 secondary outcomes
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
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 24 Dec 2015.
- Background: PubMed 19884372Regev-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.
- Background: PubMed 21820571Regev-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.
- Background: PubMed 21261931Barraud 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.
- Background: PubMed 18657857Charville 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.
- Background: PubMed 18313512Ramritu 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.
- Background: PubMed 22508462Siddiq 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.
- Background: PubMed 24501490Parida 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.
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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.
David Greenberg, prof. study chair
ENOX
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nitric Oxide impregnated catheter in people with Urinary Tract Infection and Bacteriuria, run by Enox Israel Ltd.
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 5 inclusion and 8 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 24 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Number of participants with adverse events associated with Nitric Oxide impregnated catheters (time frame: 30-45 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02277171, which also lists 7 linked publications.
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 24 Dec 2015.