Impact of Prontosan Wound Gel X on Surgical Site Infections in Cardiac Surgery

Background Surgical site infections (SSIs) remain one of the most frequent and impactful healthcare-associated infections (HAIs) in cardiac surgery, particularly in patients undergoing median sternotomy. Despite advancements in perioperative care and infection prevention protocols, SSIs continue to pose a substantial burden on postoperative recovery, patient safety, and healthcare systems.

Superficial SSIs, which involve the skin and subcutaneous tissues, represent a significant proportion of these infections and are often underestimated in terms of their clinical implications. According to global estimates, the incidence of superficial SSIs following cardiac surgery ranges from 5% to 12%, depending on the patient population, surgical complexity, and adherence to infection control measures (Cardiothoracic Interdisciplinary Research Network et al., 2024). In Italy, recent surveillance data suggest a comparable incidence, with rates in cardiac surgery patients undergoing sternotomy reaching approximately 10-12%, particularly in high-risk groups.

The clinical consequences of superficial SSIs are far from negligible. They are associated with prolonged hospital stays, increased use of antibiotics, elevated risk of wound dehiscence, and, in some cases, progression to deeper infections such as mediastinitis. Moreover, these complications may require additional surgical interventions and intensive care, further straining healthcare resources. Economically, SSIs impose a considerable cost burden on hospitals and national health systems. Extended hospitalizations and re-operations increase direct medical costs, while indirect costs related to loss of productivity and reduced quality of life further amplify the impact. Preventing even a modest proportion of SSIs could translate into substantial cost savings and improved patient outcomes.

The development of superficial SSIs following cardiac surgery is a multifactorial phenomenon influenced by a complex interplay of intrinsic patient characteristics, procedural variables, and anatomical considerations related to the surgical approach. Intrinsic risk factors include advanced age, elevated body mass index (BMI), and the presence of comorbid conditions such as diabetes mellitus, chronic obstructive pulmonary disease (COPD), peripheral vascular disease, and immunosuppression.

These factors could compromise wound healing, increase susceptibility to infection, and impair the host immune response, thereby predisposing patients to postoperative complications, including SSIs. Procedural factors also contribute substantially to infection risk. Prolonged operative time, excessive intraoperative bleeding, use of foreign materials (e.g., sternal wires or grafts), and the overall complexity of the surgical intervention are all associated with higher rates of SSIs. Moreover, suboptimal wound management practices, including insufficient skin antisepsis or improper application of dressings, may further elevate infection risk.

Median sternotomy, the standard approach for many cardiac surgeries, presents unique challenges in SSI prevention. The anatomical location of the incision, midline, overlying the sternum, exposes it to mechanical stress from coughing, movement, or respiratory support. The surgical site is also adjacent to critical mediastinal structures, increasing the clinical severity of any infection that progresses beyond the superficial layers. Additionally, the central location of the wound increases the likelihood of contamination through hand contact or dressing manipulation during routine postoperative care.

Current SSI prevention strategies in cardiac surgery rely on a multifaceted bundle approach, integrating evidence-based measures applied throughout the perioperative continuum. These strategies aim to reduce microbial contamination, optimize host defense mechanisms, and promote proper wound healing. Intraoperative prevention protocols include the administration of prophylactic antibiotics within one hour before incision, appropriate hair removal (if necessary), strict adherence to sterile technique, and the use of antiseptic solutions such as chlorhexidine-alcohol for skin preparation. Maintaining normothermia, glycemic control, and adequate oxygenation are also recognized as critical intraoperative strategies endorsed by international guidelines, including those from the WHO and CDC. Postoperative measures focus on maintaining a clean and protected wound environment, minimizing unnecessary dressing changes, and ensuring close monitoring for early signs of infection. Patient education and staff training in wound care management also play a central role in SSI prevention.

Within this framework, topical wound care products and advanced dressings are increasingly utilized to enhance the physical barrier against microbial infiltration and to modulate the local wound environment. Antimicrobial gels, including those containing polyhexanide or other antiseptic agents, are applied directly to the surgical wound before dressing placement. These products may reduce bacterial colonization at the incision site, mitigate local inflammation, and support early tissue healing. In particular, polyhexanide-based gels offer a dual mechanism of action: antiseptic activity against a broad spectrum of pathogens and disruption of biofilm formation, which is a major contributor to chronic infection and delayed healing. When incorporated into standardized protocols, these products may complement systemic antibiotic prophylaxis and contribute to reducing superficial SSIs, especially in high-risk procedures such as cardiac surgery via sternotomy.

Although current SSI prevention protocols are comprehensive and multifactorial, superficial SSIs remain prevalent in cardiac surgery, particularly following median sternotomy. Despite the promising properties of polyhexanide-based topical agents, including broad-spectrum antimicrobial activity and biofilm disruption, their use remains largely empirical, with limited evidence from prospective, real-world studies evaluating their clinical impact. Most available data derive from heterogeneous patient populations or non-comparative case series, leaving a gap in the high-quality evidence required to support systematic integration into standard surgical care pathways. This evidence gap is especially significant given the high burden of SSIs on both patients and healthcare systems. In cardiac surgery, even superficial wound infections can lead to serious complications, including delayed recovery, reoperations, and prolonged hospitalizations, with substantial clinical and economic consequences. Given the anatomical vulnerability of sternotomy wounds and the frequency of mechanical stress in the postoperative period, targeted prophylactic strategies addressing the wound environment at the point of closure may provide critical additional protection.

Study design This is a single-cohort, post-market study employing an observational, single-arm design with adaptive stopping rules. The study is designed to evaluate the real-world effects of intraoperative application of Prontosan Wound Gel X on the occurrence of SSIs in adult patients undergoing cardiac surgery via median sternotomy. Also, the adaptive component does not involve patient-level treatment decisions but solely concerns the possibility of an early termination of enrolment once sufficient evidence on the primary endpoint has been reached.

Given the post-marketing and non-comparative nature of the study, the study does not involve randomization or a control group. Instead, all eligible patients will receive the Prontosan Wound Gel X application as part of a standardized intraoperative wound management protocol. The primary objective is to generate preliminary, real-world data on the potential benefits of Prontosan Wound Gel X in preventing superficial SSIs and to inform the design of future comparative trials.

The study adopts a flexible adaptive approach, allowing interim analyses to be conducted after every 100 patients complete their hospitalization period. These analyses will be used to: (i) evaluate early trends in SSI occurrence; (ii) assess feasibility in terms of protocol adherence and data quality; (iii) inform possible protocol modifications, including adjustments to sample size, if predefined thresholds are met. The protocol is designed to adhere to the The Adaptive designs CONSORT Extension (ACE) statement. In other words, based on these analyses, the Steering Committee will evaluate whether the pre-specified statistical threshold for the primary endpoint has already been achieved, in which case further enrolment will be discontinued to avoid exposing additional patients beyond what is ethically and scientifically necessary.

This adaptive feasibility framework allows for data-driven optimization of the study trajectory while maintaining methodological rigor. It is particularly suited to exploratory, post-marketing studies where the effect size, population heterogeneity, and operational logistics are not fully established.

The overall duration of patient participation corresponds to their entire hospital stay, from surgery to discharge, in order to capture all relevant early postoperative outcomes, including superficial SSIs, hospital length of stay, and re-do surgeries. No additional follow-up beyond discharge is planned.

Adaptive Feasibility Framework This study adopts an adaptive feasibility design, which allows for prospectively planned modifications to selected trial components based on accumulating data obtained during interim analyses. Adaptive designs are particularly suitable for exploratory, post-marketing studies where uncertainties exist regarding the effect size, population response, and operational logistics. In this context, the adaptive framework is intended to optimize the study trajectory by enabling the evaluation of early efficacy signals, assessing feasibility parameters such as protocol adherence and data quality, and informing potential refinements to the protocol, including adjustments to sample size.

Interim analyses will be conducted after every 100 patients have completed their hospitalization period. These analyses will focus primarily on the observed rate of superficial SSIs in relation to the pre-specified target threshold of 8%, as well as on the completeness and consistency of collected data and the emergence of any unexpected safety signals. Based on these interim results, the study steering committee may recommend continuation as planned, sample size recalibration, protocol modifications, or early termination of the trial. Decisions will be made in accordance with pre-specified adaptation rules designed to preserve statistical validity and scientific integrity.

The adaptation mechanism will follow a group sequential structure, with appropriate statistical safeguards, including alpha-spending functions, to control the overall type I error rate. The design is aligned with the regulatory principles outlined in the methodological and reporting standards set forth by the Adaptive Designs CONSORT Extension (ACE) statement. This approach provides both flexibility and rigor, ensuring that the study remains responsive to emerging data while maintaining transparency and reproducibility in its design and conduct.

Steering Committee

The Steering Committee will not perform any patient-level clinical or safety monitoring. Its exclusive role is to evaluate, at pre-specified interim analyses (every 100 patients), whether the primary endpoint has been reached with sufficient statistical robustness. The following rules will apply:

* Continuation of enrolment: if the observed incidence of superficial SSIs remains above the predefined threshold (≤8%) or statistical precision is not yet sufficient to draw valid conclusions. * Early termination of enrolment: if the primary endpoint is achieved (observed incidence of superficia

• Length of Hospital Stay [Срок оценки: From the date of surgery to the date of hospital discharge, assessed for up to 30 days.]
• Incidence of Re-do Surgery [Срок оценки: From the date of surgery until hospital discharge, assessed for up to 30 days.]
• Protocol Adherence [Срок оценки: From intraoperative period through postoperative hospitalization until discharge, assessed for up to 30 days.]
• Data Completeness [Срок оценки: Assessed from the intraoperative period through discharge, for up to 30 days.]
• Acceptability of Gel Use [Срок оценки: From intraoperative period through postoperative hospitalization until discharge, for up to 30 days.]
• Product-Related Adverse Events [Срок оценки: From the day of surgery until discharge, assessed for up to 30 days.]