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.

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.

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.

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Masking Description

This study is triple-blinded. Study participants, healthcare providers responsible for catheter insertion and clinical care, and outcome assessors are blinded to treatment allocation.

The investigational device (COPESILCUP) and the control device (standard silicone urinary catheter) are visually indistinguishable and are packaged and labeled using coded identifiers. Randomization codes are generated and maintained by personnel not involved in patient care, outcome assessment, or data analysis.

Blinding is maintained throughout the study period until completion of data collection and primary analyses. Unblinding is permitted only in the event of a serious adverse event when knowledge of the assigned device is necessary for patient safety.