Clinical Assessment of a Biofilm-Disrupting Agent for the Management of Chronic Wounds Compared With Standard of Care

A Therapeutic Approach

Daniel Kim, MD; William Namen II, DPM; January Moore, BA; Mauricia Buchanan, BSN; Valerie Hayes, PhD; Matthew F. Myntti, PhD; Albert Hakaim, MD

Disclosures

Wounds. 2018;30(5):120-130. 

In This Article

Materials and Methods

Study Design

Study protocol was approved by both the Mayo Clinic Institutional Review Board (Rochester, MN) and The Schulman Institutional Review Board (Cincinnati, OH). This was a 12-week to 16-week, 2-site, prospective, randomized, open-label study of patients diagnosed with a recalcitrant chronic wound. This study compared the treatment outcomes of standard debridement with topical application of a biofilm-disrupting wound gel (experimental; BlastX; Next Science, Jacksonville, FL) versus a triple-antibiotic, maximum-strength ointment (control; Neosporin + Pain Relief; Johnson & Johnson, New Brunswick, NJ).

Patients who presented with a chronic wound had a medical evaluation prior to being screened against the protocol's inclusion/exclusion criteria. If criteria were met, patients were presented with the option to participate in the study and informed consent procedures were carried out in compliance with currently applicable patients' rights and safety regulations. The sample size was calculated to be 15 patients per group by power analysis (95% power at P = .05 comparing experimental group to control, assuming a 23% standard deviation and 32% difference), referencing the results by Wolcott.[8]

The 2 study sites were the Mayo Clinic in Jacksonville, Florida, and River City Clinical Research in Jacksonville, Florida. The study coordinators at each site enrolled and assigned participants into their respective groups in the order of enrollment per the randomization table provided by the experimental product manufacturer. Patients were randomized 1:1 to apply either the experimental or control once daily with the prescribed daily wound dressing change.

Patients randomized to the control group were required to complete 1 month of treatment comprising a screening/baseline, 2-week, and 1-month visits. After 1 month, the following occurred based on wound progression and/or the principal investigator's (PI) clinical judgment:

  1. Patient continued daily control application (8-week and 12-week visits).

  2. Patient crossed over to the experimental group with daily product application (4-week, 8-week, and 12-week visits).

Patients randomized to the experimental group were evaluated for 3 months, which comprised 5 visits: screening/baseline, 2-week, 4-week, 8-week, and 12-week (Figure 1). After the last research study visit (12-week or 16-week visits), patients could continue treatment as long as beneficial per PI judgment; no limit was set on the duration of extension. During the extension, visits were scheduled and carried out per standard clinical care. During the exit visit of the study (at the end of the treatment extension period), the wound measures were retrospectively obtained from the patients' charts.

Figure 1.

Consolidated Standards of Reporting Trials flow diagram.

Wound area measurements were assessed at weeks 0, 2, 4, 8, 12, and 16 using the Silhouette Star camera (ARANZ Medical, Christchurch, New Zealand). The primary endpoint was defined as a percentage reduction in wound area after 12 weeks of experimental treatment compared with the control.

There were 2 defined secondary endpoints for this study. The first secondary endpoint was defined as an improvement in the percentage of patients with closed wounds after 12 weeks of treatment compared with the control. The other secondary endpoint was to determine if there was a difference in the bacterial load and/or biodiversity in the wound when comparing treatments and treatment time.

Inclusion and Treatment

Patients participated in the study if they met all of the inclusion criteria and none of the exclusion criteria listed in Table 1.

At the first visit, the screening/eligibility form and enrollment checklist were completed, identification numbers were assigned, and patients were randomized into either the experimental or control group. Demographics were obtained along with wound-related history and concomitant medications.

At each visit, the patients' wounds were debrided with sharp instruments, and wound measurements and images were obtained. Measurements included wound area, volume, and depth.

Biofilm samples were obtained at baseline and after 1 month of treatment. Samples were analyzed in 2 ways: (1) by quantitative real-time polymerase-chain reaction (PCR) test for bacteria and fungi (which also included a qualitative real-time PCR test for resistance factors to vancomycin and methicillin); and (2) by DecodEX Microbial Genetic Identification Sequencing (MicroGen DX, Lubbock, TX) to detect bacterial organisms and fungal pathogens that may be present in patient specimens.

Statistics

Statistical analyses were performed using Minitab (Version 17.3.1; Minitab, Inc, State College, PA) on the intent-to-treat population. All patients who were enrolled and randomly allocated to treatment were included in the analysis and were analyzed in the groups to which they were randomized as well as in the crossover group where indicated. Statistical significance to the control was determined by analysis of variance (ANOVA) using a general linear model with factors as the treatment (experimental; control), time (0, 2, 4, 8, and 12 weeks), clinical research site (Mayo Clinic; River City Clinical Research), comorbidities, and patient. Tukey's pairwise comparisons were performed for grouping (P < .05). In the Figures, interval bars in the results section depict one-standard error and the grouping bars depict groups that are equivalent (for the healed wounds and percent of wound closure). Treatment bars that do not fall under the same grouping bar are statistically distinct (P < .05; for the healed wounds and percent of wound closure).

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