Clinical Evaluation of Copesilcup (Copesilcup)

Clinical Evaluation of the Efficacy and Safety of a Long-Term Urinary Catheter Made of PEGylated Silicone With Copper Nanoparticles for the Reduction of Urinary Tract Infections

Healthcare-associated infections (HAIs): HAIs are a problem for all institutions and countries worldwide. Currently, one of the main infections is catheter-associated urinary tract infection (CAUTI). Problem: Infection associated with permanent urinary catheters is a problem with a significant social and public health impact due to its high morbidity, mortality, and associated costs. The COPESIL technology developed in the FONDEF ID19I10113 project consists of the modification and functionalization of silicone materials through the anchoring of polyethylene glycol molecules on their surface (pegylation process). Our technology showed significant antimicrobial and anti-biofilm capacity in in vitro and in vivo models. This proposal aims to scale up COPESIL technology to a permanent urinary catheter that we have named COPESILCUP. The creation of a new device and its clinical validation will open up and revolutionize research in biomaterials. State of the art: Currently, there are a variety of urinary catheters designed to reduce the risk of infection. These include catheters impregnated with antibiotics (nitrofurantoin, minocycline, and rifampicin), silver oxide, and silver alloys. However, these catheters have little effect on the adhesion of uropathogens. The hypothesis is proposed: The use of a permanent silicone urinary catheter modified through a pegylation process that incorporates copper nanoparticles (COPESILCUP), which has antimicrobial and anti-biofilm properties, reduces the incidence of urinary tract infection in hospitalized adults who use permanent urinary catheters compared to unmodified silicone urinary catheters. The overall objective of this project is to develop a permanent silicone urinary catheter modified through a pegylation process that incorporates copper nanoparticles (COPESILCUP), which has antimicrobial and anti-biofilm properties, and to evaluate its efficacy by measuring the incidence of urinary tract infections and its safety in humans using permanent urinary catheters in a public hospital for adults. Methodology: Clinical validation of COPESILCUP in a Randomized Controlled Clinical Trial: the aim is to validate the medical device in a real patient setting in order to establish whether it is better than the standard.

Study Overview

• Status: Completed
• Conditions: Catheter-Associated Infection
• Intervention / Treatment: Device: PEGylated Silicone Urinary Catheter with Copper Nanoparticles (COPESILCUP); Device: Control Device

Detailed Description

Catheter-associated urinary tract infections (CAUTIs) are among the most common healthcare-associated infections worldwide and represent a significant burden in terms of morbidity, mortality, healthcare costs, and antimicrobial use. The risk of infection increases with the duration of catheterization and is particularly relevant in hospitalized patients and those requiring prolonged use of indwelling urinary catheters.

The pathophysiology of CAUTIs is strongly associated with the rapid formation of bacterial biofilm on the catheter surface, a process that can begin within hours to days after device insertion. Biofilm provides a protective environment for microorganisms, facilitating persistence, reducing susceptibility to antimicrobial therapy, and enabling evasion of host immune responses. Once established, biofilm contributes to recurrent infections and increases the risk of severe clinical complications.

Current preventive strategies include antimicrobial-impregnated catheters and devices coated with metals such as silver. However, these approaches have shown limited effectiveness in preventing early bacterial adhesion and biofilm formation, and may raise concerns regarding durability of effect and potential contribution to antimicrobial resistance.

COPESILCUP is an investigational medical device consisting of a medical-grade silicone urinary catheter modified through a surface functionalization strategy that incorporates copper-based structures. Copper is a well-known broad-spectrum antimicrobial element, capable of disrupting bacterial cell membranes, inducing oxidative stress, and interfering with essential microbial metabolic processes.

In this device, copper is integrated as part of the surface modification of the material, with the objective of reducing bacterial adhesion and interfering with early stages of biofilm formation. This approach targets the material-microorganism interface and aims to maintain the mechanical and functional properties of conventional silicone catheters, without relying on sustained release of antimicrobial agents into the surrounding environment.

Preclinical evaluation of this technology has included in vitro antimicrobial and anti-biofilm assays, as well as in vivo models of catheter-associated infection. These studies have demonstrated a significant reduction in bacterial colonization and biofilm formation compared to unmodified silicone surfaces, along with an adequate safety profile and material stability over the intended duration of use.

The present study is a randomized, controlled, parallel-group clinical trial with triple blinding, designed to evaluate the efficacy and safety of COPESILCUP compared to a standard silicone urinary catheter under real clinical conditions. Triple blinding (participants, healthcare providers, and outcome assessors/statisticians) is implemented to minimize performance, detection, and analytical bias, thereby strengthening the internal validity of the study.

Eligible participants are adult patients requiring indwelling urinary catheterization in a hospital setting. Subjects are randomly assigned in a 1:1 ratio to receive either the investigational device or a standard silicone catheter, using a structured allocation strategy to ensure balance between groups in terms of relevant clinical factors and baseline risk.

The study incorporates a comprehensive evaluation framework that integrates both clinical and microbiological endpoints. The primary outcome is the incidence of catheter-associated urinary tract infection (CAUTI), defined according to standardized diagnostic criteria. Secondary outcomes include bacteriuria, time to first detectable colonization, microbiological characterization of uropathogens, and safety outcomes related to device use.

A key methodological feature of this study is the implementation of longitudinal microbiological monitoring. Urine samples are collected at baseline and at predefined intervals during follow-up, including early time points after catheter insertion. This strategy allows characterization of the temporal dynamics of bacterial colonization and provides insight into early events associated with biofilm formation.

By integrating early microbiological changes with clinically relevant outcomes, the study design enables a more sensitive and mechanistically informed evaluation of device performance. This is particularly relevant for surface-based technologies, where the primary effect may occur during early stages of bacterial adhesion and biofilm prevention, prior to the development of clinically overt infection.

Participants are followed throughout the duration of catheter use, with clinical and microbiological assessments conducted at protocol-defined intervals. The follow-up period is aligned with standard clinical practice, supporting external validity and applicability of the findings.

Statistical analysis will be performed under an intention-to-treat framework, preserving the benefits of randomization. Both incidence-based comparisons and time-to-event analyses will be used to evaluate differences between study groups.

An interim analysis is planned under predefined criteria to assess safety and potential differences in efficacy, without compromising study integrity or blinding.

Methodological and scientific added value:

This study incorporates several methodological strengths, including a randomized triple-blind design, structured allocation, and integration of clinical and microbiological endpoints.

Importantly, the study explicitly addresses the temporal relationship between catheter insertion, early bacterial adhesion, biofilm formation, and subsequent infection. This temporal dimension is central to CAUTI pathogenesis and has been insufficiently addressed in prior clinical studies.

By combining longitudinal microbiological monitoring with clinically relevant outcomes, the study provides a more comprehensive and biologically informed assessment of device performance, increasing sensitivity to detect early effects and improving interpretation of results.

Additionally, the investigational strategy is based on modification of material surface properties rather than the release of antimicrobial agents, representing a non-pharmacological approach to infection prevention. This approach may offer advantages in terms of durability, safety, and reduced contribution to antimicrobial resistance.

The results of this study are expected to contribute to the development of next-generation medical devices aimed at preventing healthcare-associated infections and addressing a critical unmet need in clinical practice.

• Study Type: Interventional
• Enrollment (Actual): 256
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Chile
  • Santiago Metropolitan
    • Ñuñoa, Santiago Metropolitan, Chile, 750000
      • WMAS SpA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adult patients (≥18 years of age).
• Hospitalized patients from medical, surgical, emergency, operating room, or intensive care units.
• Patients with clinical indication for permanent urinary catheterization (Catéter Urinario Permanente, CUP).
• Patients able to provide written informed consent, or consent provided by a legally authorized representative.

Exclusion Criteria:

• History of urinary tract infection prior to hospitalization within the last month without a post-treatment follow-up urine culture.
• Patients with a positive initial urine culture at the time of permanent urinary catheter (CUP) insertion.
• Patients with a history of allergy to silicone or to any component of the COPESILCUP device.
• Patients unable to complete follow-up, for example, due to transfer to another healthcare facility within the first 72 hours after stabilization.
• Patients with psychiatric conditions that may result in non-professional manipulation of the urinary catheter.
• Patients with a history of prior urinary tract colonization.
• Patients with a history of urinary or renal instrumentation or surgical intervention within the last month.
• Patients with pre-existing abnormalities of the pyeloureteral or urinary system.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: COPESILCUP Urinary Catheter; Participants assigned to this group receive an indwelling urinary catheter made of medical-grade silicone with surface modification incorporating copper-based nanoparticles (COPESILCUP). The catheter is inserted and managed according to standard clinical practice for urinary catheterization.	Device: PEGylated Silicone Urinary Catheter with Copper Nanoparticles (COPESILCUP); The intervention consists of the use of a permanent urinary catheter made of medical-grade silicone modified through a PEGylation process incorporating copper nanoparticles (COPESILCUP). The investigational catheter is inserted following standard sterile clinical procedures for permanent urinary catheterization, in accordance with institutional infection prevention protocols. Catheter insertion, fixation, maintenance, and removal are performed by trained nursing staff using a closed urinary drainage system. Urine samples are collected at the time of catheter insertion (baseline), every 7 days during catheterization, and at catheter removal for urinalysis and urine culture. Participants are monitored throughout catheter use for the occurrence of catheter-associated urinary tract infection and for device-related adverse events. No additional procedures beyond standard clinical care for permanent urinary catheter use are required. The intervention differs from standard care only in the; Other Names: PEGylated Silicone Urinary Catheter with Copper Nanoparticles; COPESIL Modified Urinary Catheter; COPESILCUP
Other: Standard Silicone Urinary Catheter; Participants assigned to this group receive a standard indwelling urinary catheter made of medical-grade silicone without surface modification. The catheter is inserted and managed according to routine clinical practice.	Device: Control Device; The control intervention consists of the use of a standard permanent urinary catheter made of medical-grade silicone without surface modification. The catheter is inserted following standard sterile clinical procedures for permanent urinary catheterization and managed according to routine hospital care protocols. Catheter insertion, fixation, maintenance, and removal are performed by trained nursing staff using a closed urinary drainage system. Urine samples are collected at baseline, during catheter use according to institutional protocols, and at catheter removal for urinalysis and urine culture. Participants are monitored during catheter use for the occurrence of catheter-associated urinary tract infection and for device-related adverse events. No additional procedures beyond standard clinical care for permanent urinary catheter use are required.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Catheter-Associated Urinary Tract Infection (CAUTI)	Incidence of catheter-associated urinary tract infection, defined as the presence of a positive urine culture combined with clinical and/or laboratory findings consistent with urinary tract infection, assessed during the period of permanent urinary catheter use.	At Day 1 (baseline), Day 7, Day 14, Day 21, and Day 28 (up to 30 days) of follow-up or until catheter removal, whichever occurs first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Positive Urine Culture	Time elapsed from permanent urinary catheter insertion to the first documented positive urine culture during follow-up.	At Day 1 (baseline), Day 7, Day 14, Day 21, and Day 28 (up to 30 days).
Relative Risk of Catheter-Associated Urinary Tract Infection	Comparison of the cumulative incidence of catheter-associated urinary tract infection between the intervention group (COPESILCUP) and the control group (standard silicone catheter).	At Day 1 (baseline), Day 7, Day 14, Day 21, and Day 28 (up to 30 days).
Incidence of Device-Related Adverse Events	Frequency of adverse events potentially related to the use of the urinary catheter, including local irritation, allergic reactions, or other device-related complications.	From Day 1 (catheter insertion) up to 30 days or until catheter removal, whichever occurs first

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiological Profile of Uropathogens	Identification and distribution of bacterial species isolated from positive urine cultures obtained at baseline and during follow-up.	At Day 1 (baseline), Day 7, Day 14, Day 21, and Day 28 (up to 30 days).

Collaborators and Investigators

• Sponsor: WMAS SpA
• Collaborators: Comisión Nacional de Investigación Científica y Tecnológica; Hospital del Salvador; Instituto Nacional de Neurología y Neurocirugía; Universidad Bernardo O'Higgins

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Actual): August 30, 2024
• Study Completion (Actual): August 30, 2024

Study Registration Dates

• First Submitted: January 6, 2026
• First Submitted That Met QC Criteria: April 7, 2026
• First Posted (Actual): April 15, 2026

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Urinary Tract Infection; Catheter-Associated Urinary Tract Infection; Healthcare-Associated Infection
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Infections; Iatrogenic Disease; Pathological Conditions, Signs and Symptoms; Urinary Tract Infections; Cross Infection; Catheter-Related Infections
• Other Study ID Numbers: 001 (Buy Pharma Ecza Deposu San. Tic. Ltd.); IT21I0048 (Other Grant/Funding Number: National Research and Development Agency of Chile)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: confidencial

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No