A Clinical Trial Design for Evaluating Topical Antimicrobials in Chronic Wounds: The BLEU Trial.

Chronic wound management is a global challenge. Millions of patients suffer from nonhealing ulcers and health systems are overwhelmed by the growing demand for treatment. Despite the prevalence of chronic wounds, the emergence of wound centers and specialized physicians is a recent phenomenon. Likewise, clinical research in wound healing is in its infancy. To date, many of the products in wound care have little or no clinical evidence. The field needs standardized clinical trial design, endpoints recognized by clinicians and payers, and improved overall clinical evidence. Wound healing is impeded by the presence of bacterial biofilms, which exist in most chronic wounds. It is not surprising that biofilm disruption is the focus of wound management and essential to the healing process. Multiple laboratory and preclinical studies demonstrate promising efficacy of several antimicrobials in treating biofilms; however, the field lacks in vivo clinical studies. In addition, a standardized trial design to evaluate efficacy of antimicrobials in chronic wounds does not exist. The advent of new diagnostic technologies, such as fluorescence imaging, has led to clinical trial designs that are reliable, easier to conduct, and cost efficient. The protocol presented here describes a randomized controlled double-blind trial designed to evaluate antiseptics in chronic wounds.

A prospective clinical pilot study comparing two post-operative dressings in the treatment of surgical incisions in volunteers.

OBJECTIVE: Surgical site infections (SSIs) are one of the leading causes of post-operative morbidity and mortality worldwide. The original post-operative dressing, gauze taped in place, did not protect the incision from contamination. A recent clinical trial demonstrated that transparent films were superior to gauze in reducing SSIs. Transparent films are semi-occlusive (semi-permeable, transparent). They protect the incision from contamination; however, one of the drawbacks of current films is that they may become dislodged during daily activities, such as showering. Patients may not realise that the integrity of the dressing has been compromised, leading to soiling of the incision and possible infection. DrySee (DrySee Inc., US) is a novel film dressing with a colorimetric indicator that alerts the patient when the dressing has been compromised. METHOD: This trial compared the film dressing with the indicator (DSD) to a commonly used post-operative dressing comparator (Tegaderm + Pad; 3M, US). A 1.5cm incision was made in the volar forearm of volunteers. The incisions were randomly treated with the DSD or comparator dressing. RESULTS: A cohort of 20 volunteer patients was recruited. The DSD had a greater wear time and patients reported that the DSD dressing stayed in place better during activities compared to the comparator. CONCLUSION: Overall, 75% of patients preferred DSD and 25% preferred the comparator.

A novel debridement device for the treatment of hard-to-heal wounds: a prospective trial.

OBJECTIVE: Debridement, the removal of nonviable tissue, forms the foundation of wound care practice. Clinicians have a variety of debridement methods at their disposal: sharp, biologic, enzymatic, autolytic and mechanical. The choice of debridement technique depends on the patient care setting, ulcer type and the clinician's experience, training, comfort level and licensure. This prospective study evaluated a novel debridement instrument, EZ-Debride (MDM Ventures, US). Cutting flutes on the head of the tool permit uniform removal of dead tissue while lessening the risk of deeper injury. It may also minimise pain during the debridement procedure. METHOD: Subjects with hard-to-heal wounds, drawn from a single wound care centre, participated in this institutional review board-approved prospective clinical study. Pain was measured before, during and after debridement using a numerical scale. Assessment of bacterial burden using fluorescence imaging (MolecuLight, Canada) was performed before and after debridement. RESULTS: Enrolment of 10 male and 12 female subjects, with a total of 28 wounds, was carried out over a two-month period by two investigators at a single institution. The average age of subjects was 64 years (range: 22-95 years). The average wound duration was 29 weeks (range: 6-142 weeks). Wound types included diabetic foot, venous leg and pressure ulcers, post-surgical and traumatic wounds. The average pain score at the time of enrolment was 3.9. Subjects reported an average increase in pain with debridement of 0.6 points (range: 0-8). Fluorescence imaging demonstrated a reduction in bacterial load in 69% of cases, with complete resolution in 19% of wounds. Haemostasis was achieved with direct pressure in all cases and the only adverse event was a wound infection that occurred four days after debridement. CONCLUSION: The results suggest that this novel debridement tool can safely remove nonviable tissue with minimal discomfort and reduce bacterial burden similar to results achieved by sharp debridement.

Diagnostic Accuracy of Point-of-Care Fluorescence Imaging for the Detection of Bacterial Burden in Wounds: Results from the 350-Patient Fluorescence Imaging Assessment and Guidance Trial.

Objective: High bacterial load contributes to chronicity of wounds and is diagnosed based on assessment of clinical signs and symptoms (CSS) of infection, but these characteristics are poor predictors of bacterial burden. Point-of-care fluorescence imaging (FL) MolecuLight i:X can improve identification of wounds with high bacterial burden (>104 colony-forming unit [CFU]/g). FL detects bacteria, whether planktonic or in biofilm, but does not distinguish between the two. In this study, diagnostic accuracy of FL was compared to CSS during routine wound assessment. Postassessment, clinicians were surveyed to assess impact of FL on treatment plan. Approach: A prospective multicenter controlled study was conducted by 20 study clinicians from 14 outpatient advanced wound care centers across the United States. Wounds underwent assessment for CSS followed by FL. Biopsies were collected to confirm total bacterial load. Three hundred fifty patients completed the study (138 diabetic foot ulcers, 106 venous leg ulcers, 60 surgical sites, 22 pressure ulcers, and 24 others). Results: Around 287/350 wounds (82%) had bacterial loads >104 CFU/g, and CSS missed detection of 85% of these wounds. FL significantly increased detection of bacteria (>104 CFU/g) by fourfold, and this was consistent across wound types (p < 0.001). Specificity of CSS+FL remained comparably high to CSS (p = 1.0). FL information modified treatment plans (69% of wounds), influenced wound bed preparation (85%), and improved overall patient care (90%) as reported by study clinicians. Innovation: This novel noncontact, handheld FL device provides immediate, objective information on presence, location, and load of bacteria at point of care. Conclusion: Use of FL facilitates adherence to clinical guidelines recommending prompt detection and removal of bacterial burden to reduce wound infection and facilitate healing.

Comparing near infrared spectroscopy and transcutaneous oxygen measurement in hard-to-heal wounds: a pilot study.

OBJECTIVE: Oxygen plays an integral role in all phases of the wound healing process and tissue oxygenation is a key determinant of wound healing. A comprehensive evaluation of patients with hard-to-heal wounds must include measurement of oxygenation in and around the area of skin breakdown. The current gold standard, transcutaneous oxygen measurement (TCOM), has numerous drawbacks and as a result has fallen into disuse. METHOD: This study compared measurement of tissue oxygenation of near infrared spectroscopy (NIRS) with TCOM in patients with acute and hard-to-heal wounds. The Shapiro-Wilk test was used to evaluate the normality of the data. The level of agreement between NIRS and TCOM was determined using Bland-Altman analysis. The relationship between TCOM and NIRS was examined using Pearson correlation. RESULTS: A total of 24 observations were obtained from 10 patients using TCOM and NIRS. The weighted mean partial pressure of oxygen (pO2) in the study population was 39.54mmHg (8.96 standard deviation). Bland-Altman analysis showed that mean difference was positive (18.75), suggesting an overestimation of oxygen measurements using TCOM compared with NIRS. The oxygen levels measured by TCOM and NIRS showed a strong correlation (r=0.74). CONCLUSION: The wound and hyperbaric community would benefit from a simplified procedure for measuring tissue oxygenation. These findings suggest a strong trend toward correlation between NIRS and TCOM. A further study in a larger population is recommended. NIRS offers several advantages over TCOM. Clinicians have immediate point-of-care visualisation of tissue oxygenation using a handheld device. The procedure takes minutes to perform and is less operator-dependent than TCOM. Finally, NIRS allows measurement of oxygenation in the wound bed, while TCOM does not.

Real-time bacterial fluorescence imaging accurately identifies wounds with moderate-to-heavy bacterial burden.

OBJECTIVE: Clinical evaluation of signs and symptoms (CSS) of infection is imperative to the diagnostic process. However, patients with heavily colonised and infected wounds are often asymptomatic, leading to poor diagnostic accuracy. Point-of-care fluorescence imaging rapidly provides information on the presence and location of bacteria. This clinical trial (#NCT03540004) aimed to evaluate diagnostic accuracy when bacterial fluorescence imaging was used in combination with CSS for identifying wounds with moderate-to-heavy bacterial loads. METHODS: Wounds were assessed by study clinicians using NERDS and STONEES CSS criteria to determine the presence or absence of moderate-to-heavy bacterial loads, after which the clinician prescribed and reported a detailed treatment plan. Only then were fluorescence images of the wound acquired, bacterial fluorescence determined to be present or absent and treatment plan adjusted if necessary. RESULTS: We examined 17 VLUs/2 DFUs. Compared with CSS alone, use of bacterial fluorescence imaging in combination with CSS significantly improved sensitivity (22% versus 72%) and accuracy (26% versus 74%) for identifying wounds with moderate-to-heavy bacterial loads (≥104 CFU/g, p=0.002). Clinicians reported added value of fluorescence images in >90% of study wounds, including identification of wounds incorrectly diagnosed by CSS (47% of study wounds) and treatment plan modifications guided by fluorescence (73% of study wounds). Modifications included image-guided cleaning, treatment selection, debridement and antimicrobial stewardship. CONCLUSION: Findings from this pilot study suggest that when used in combination with CSS, bacterial fluorescence may: (1) improve the diagnostic accuracy of identifying patients with wounds containing moderate-to-heavy bacterial loads and (2) guide more timely and appropriate treatment decisions at the point-of-care.