Efficacy of a Bioresorbable Matrix in Healing Complex Chronic Wounds

An Open-Label Prospective Pilot Study

Sarah W. Manning, MD; David A. Humphrey, MD; William R. Shillinglaw, DO; Eric Crawford; Gaurav Pranami, PhD; Ankit Agarwal, PhD; Michael J. Schurr, MD

Disclosures

Wounds. 2020;32(11):309-318. 

In This Article

Materials and Methods

Matrix Intervention

The matrix is cleared by the US Food and Drug Administration (FDA) as a wound dressing indicated for the management of surgical wounds, burn wounds, and chronic ulcers; it is manufactured by Imbed Biosciences, Inc in an FDA-registered International Organization Standard (ISO) 13485 certified facility. The matrix is an electron beam-sterilized, single-use, absorbent ultrathin polymeric matrix (thickness, 20 μm). It is composed primarily of a bioresorbable polymer (polyvinyl alcohol) with a multilayer polymeric surface coating containing ionic and metallic silver (0.16 mg/in2). When placed on a moist wound surface, the matrix absorbs wound fluid and maintains a moist wound healing environment that aids in the removal of nonviable tissue from the wound (autolytic debridement),[21] the benefits of which could include reduced pain, accelerated neovascularization, and prevention of tissue dehydration.[22] According to its published instructions for use (IFU), biocompatibility of the matrix has been documented through appropriate in vitro and in vivo ISO 10993 standard tests, including cytotoxicity, acute systemic toxicity, subacute/subchronic toxicity, acute intracutaneous reactivity, skin sensitization, and tissue implantation tests. Sustained antimicrobial activity of the matrix has been demonstrated for up to 3 days by relevant standard in vitro microbiological assays in simulated wound fluid. The matrix has been reported to kill more than 4 log10 colony-forming units of microbes most frequently associated with wound infections within 24 hours, including Staphylococcus aureus (ATCC 6538), methicillin-resistant S aureus (ATCC 33591), vancomycin-resistant enterococci (ATCC 55175), Pseudomonas aeruginosa (ATCC 9027), Escherichia coli (ATCC 8739), Klebsiella pneumoniae (ATCC 4352), Candida tropicalis (ATCC 750), and Candida albicans (ATCC 10231). The matrix is tested to be nonpyrogenic as well as reported to bioresorb within 7 days.[17]

Study Design

This clinical study was conducted in accordance with Title 21 of the Code of Federal Regulations and the Declaration of Helsinki as well as its subsequent amendments and the laws of the United States, where applicable. It was conducted at Mission Hospital's 800-bed southeastern tertiary care center in Asheville, North Carolina, under a protocol reviewed and approved by the Mission Hospital IRB. The patient population included patients referred to the Wound Healing and Hyperbaric Center at Mission Hospital for wound management. This study was designed as a prospective examination of the efficacy and tolerability of the matrix when used in patients with various nonhealing complex chronic wounds that have not responded to protocols of care (including a variety of traditional antimicrobial dressings and ointments and antibiotics). Upon referral to the wound center, the clinical investigator (DH) assessed the patient's medical history, ulcer etiology, and alignment with the study inclusion and exclusion criteria (Table 1) to determine potential eligibility for the study. Patients provided written informed consent at the time of initial evaluation and received the matrix at their initial dressing change.

The clinical investigator conducted baseline and follow-up assessments of all patients. The clinical investigator continued the previously prescribed protocol of care for each wound and added the matrix as a primary wound contact dressing to the treatment plan. Any additional antibiotics or primary antimicrobial dressings were discontinued. Briefly, wounds were gently cleaned and irrigated with sterile saline. Surgical or enzymatic debridement protocols were performed, if clinically indicated, to remove excessive necrotic tissue. The matrix was cut to be slightly larger than the size of the wound and applied directly to the moist wound tissue surface. The matrix quickly absorbed moisture and transformed into a soft conforming gel sheet. Multiple sheets of the matrix were tiled if needed to cover the entire wound area. The same secondary dressing used in the patient's ongoing treatment plan was used to cover the matrix. Any specific treatment plan in ongoing protocols of care were continued, including negative pressure wound therapy or compression wraps. No cellular- and/or tissue-based products were used in this study.

The matrix was reapplied once every 3 days, as suggested in the IFU product insert. The matrix was reapplied by the clinical investigator on each patient visit when secondary dressings were changed, depending on the wound healing progression or when clinically indicated (eg, leakage, excessive bleeding, increased pain). The matrix was reapplied at least once weekly in all protocols of care as it is reported to bioresorb within 7 days. No additional antibiotics or topical antimicrobials were administered.

During dressing changes, the secondary dressing was removed, and the wound bed was gently irrigated with sterile saline solution to remove any necrotic tissue. Any residual matrix left in the wound was not removed due to its bioresorbable nature; ultimately, it was cleared from the wound bed by migrating macrophages that break it down and digest it as the wound heals.[16,17]

Study assessments included wound closure (measured as percent of wound area reduction), frequency of dressing changes, pain, clinical evaluation of wound infection, and adverse events (AEs). Wound measurements and photographs were obtained at each clinic visit, as was an in-house patient satisfaction survey. Wounds were photographed at each study session, and the digital photographs were visualized with ImageJ software (National Institutes of Health) by an independent investigator blinded to the treatment to measure total wound area. Data from the study assessments were collected on a separate data collection sheet for each patient. The clinical investigator ensured that data collection sheets were completed properly. All source documents, photo documentation of wounds, and data collection sheets were maintained in individual patient files. Since these wounds were nonhealing at baseline, acceleration in wound healing from the use of the matrix was measured as percent of wound area reduction, according to FDA guidance.[23]

The primary endpoint was the percent of wound area reduction at 3 weeks from baseline. The 3-week time point was chosen based on prior clinical experience of the authors in which significant improvement in wound healing was observed in the nonhealing wounds. Furthermore, such complex wounds require multimodal treatment plans and might not respond to a change in topical antimicrobial dressing alone. Therefore, the clinical investigator recommended that if a wound does not respond to the use of the matrix in protocols of care within 3 weeks, it would be removed from the study. The treatment with the matrix continued for up to 12 weeks, at the discretion of the physician, or until the patient no longer visited the wound care center.

The secondary endpoints were percent of wound area reduction at 12 weeks from baseline, pain, incidence of infection, and patient satisfaction. Patients whose wounds were treated with the matrix but did not heal completely within 12 weeks continued to be seen by the clinical investigator.

The AEs were documented and reported in accordance with FDA rules and regulations. The time of onset (if known), duration, intensity, relationship to the test product, treatment, and follow-up were recorded. The clinical investigator assessed causality between the AE and the administration of the matrix. An AE was considered not related if the event was most likely produced by other factors, such as the patient's clinical condition, intercurrent illness, or concomitant medications or procedures. In addition, an AE was considered not related if the event did not follow a known response pattern to the matrix or the temporal relationship of the event to the administration of the matrix made a causal relationship unlikely; a lack of an alternative explanation for the AE was also considered. An AE was considered related if a reasonable temporal sequence of the event with the administration of the matrix existed. Also, on the basis of the known pharmacological action of the matrix, an AE was considered related if the known or previously reported AE to the matrix seemed likely, or if there was a lack of alternative explanation for the AE.

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