Durability of an Advanced Skin Protectant Compared With Other Commercially Available Products in Healthy Human Volunteers

Background. A new skin protectant with improved adhesion to denuded skin and resistance to wash off has been developed to protect skin from incontinence-associated dermatitis (IAD) or general loss of skin integrity. Objective. This controlled, randomized, prospective, open-label study determines the durability of the new protectant when applied to intact skin in 21 healthy human volunteers and compares it to 3 other products used for similar clinical indications. Materials and Methods. Eight 0.75-in circles of black carbon pigment were applied to the bilateral forearms (4 per arm to allow for duplicates) of the participants and covered with the various products. Participants conducted normal routine activities over 7 days. Photographs were taken and a test site assessment was completed before and after application of the products on day 0 and at days 1, 2, 3, 4, and 7 to evaluate pigment loss over time. Carbon integrated optical density (CIOD) was measured under the assumption that a loss of pigment correlated with a loss of the protective product. These data were used to calculate the percent barrier remaining over time. Results. The percent of intact film was significantly greater (P < .05) from day 3 onwards for the new skin protectant compared with the other 3 products. The new product showed no significant change in CIOD (P = .46) from day 1 through day 7, indicating no meaningful wear over time. The other 3 products showed significant changes in CIOD (P < .01) beginning at either day 2 or day 3. Conclusions. The new skin protectant was more durable than the other products tested. It remained in place for up to 7 days for all participants, whereas the other products had < 50% remaining on the skin by that time point.

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The skin is the protective layer of the body and provides an important barrier to pathogens, irritants, water loss, and environmental threats. Various conditions can damage the skin and breach the integrity of the barrier, resulting in inflammation, disruption of epidermal integrity, pain, and increased risk of infection. One example of such a condition is incontinence, which can lead to skin damage due to excessive moisture, high pH, and, in the case of fecal incontinence, the presence of fecal enzymes. Skin damage resulting from incontinence is referred to as incontinence-associated dermatitis (IAD) and has been reviewed in the literature.^1-6

Several products and protocols are available for skin care and various studies^7-12 and review articles^1,13 have been published. In 2015, a global expert panel published best practice principles for the management of IAD.¹⁴ This group defined the general characteristics of the ideal product for the prevention and management of IAD, which include, among others, “does not sting on application”; “transparent or can be easily removed for skin inspection”; “removal/cleansing considers caregiver time and patient comfort”; “does not increase skin damage”; and “minimizes number of products, resources, and time required to complete skin care regimen.” The challenge that remains with existing products is that they do not adhere to the denuded skin with weeping erosions that can be observed in severe cases of IAD. Barrier films work well to protect intact skin, and pastes have become the product of choice for denuded skin. However, pastes are thick and difficult to clean, causing significant discomfort for patients. They do not meet the criterion “transparent or easily removed.”¹⁴ Despite best clinical care efforts, management of IAD using current methods and products remains inadequate and does not prevent recurrence; a technological improvement is much needed.

In this paper, the investigators report on a new skin protectant based on an acrylate chemistry, which is applied as a liquid and polymerizes in situ after application to produce a breathable film capable of preventing urinary or fecal incontinence from reaching the skin surface. The customized acrylic polymers are combined with 2-octyl cyanoacrylate to create the film structure. The formulation is delivered in a nonirritating solvent, even for skin that is denuded and/or compromised by exposure to caustic bodily fluids such as urine, liquid feces, gastric fluid, and wound exudate. This product is intended to protect the skin from additional insult from incontinence and to provide an environment favorable for healing beneath the film. This formulation can adhere to both intact skin and denuded, weeping skin, as first demonstrated in a pig study.¹⁵ It also has been clinically tested in 16 patients with IAD who were followed for up to 21 days and led to a decrease in the IAD score for 13 of 16 patients (81.25%), as well as a substantial pain reduction in all 9 patients able to report pain at enrollment.¹⁶ That clinical study confirmed the product is well tolerated, adheres to denuded skin, does not sting upon application, is transparent so it allows for skin inspection, and allows for easy cleanup of incontinence while keeping patients comfortable. The authors expect it to be more effective and durable than conventional barriers when exposed to harsh bodily fluids as well as more resistant to wash off.

The aim of this research is to quantitatively assess the durability of the film-forming product on healthy human volunteers using a model over 7 days and to compare it with other commercially available products indicated for the management of IAD.

This is an open-label, randomized controlled study evaluating the durability of 4 commercially available products for the treatment of breaches in skin integrity, such as IAD, on healthy volunteers. This study was approved by the Allendale Institutional Review Board (Old Lyme, CT).

The products tested were 3M Cavilon Advanced Skin Protectant (Code A; 3M, St Paul, MN), Medline Marathon Liquid Skin Protectant (Code B; Medline Industries Inc, Northfield, IL), Smith & Nephew No-Sting Skin Prep (Code C; Smith & Nephew, Hull, UK), and Medline SurePrep No Sting Skin Protective Barrier Wand (Code D; Medline Industries Inc).

Twenty-one healthy volunteers were recruited from a pool of healthy men and women who met the inclusion/exclusion criteria. The inclusion criteria consisted of Caucasian men or women between the ages of 18 and 75 with Fitzpatrick Skin Type I, II, or III, in good general health, who were willing and able to follow all study directions. The exclusion criteria were pregnancy, nursing, or planning a pregnancy; tattoos, marks, scars, scratches, moles, freckling, uneven skin tone, or other blemishes on the test sites that would interfere with the study; a skin condition (eg, psoriasis, atopic dermatitis, etc); or known allergies or sensitivities to charcoal, solvents, or acrylates.

The method involved the use of activated carbon (Fisher Scientific, Fair Lawn, NJ), as it mimics dirt application by getting in the small pores and creases of the skin and being difficult to remove. The test products were applied over the activated carbon. It was expected that as the films wore off the skin, the carbon also would wear off. Digital photographs were used to document and calculate the amount of activated carbon and, therefore, barrier film remaining on the sites to determine durability over several days. Any observable skin reactions also were noted.

Application of pigment

On day 0, the study personnel blinded to the treatment verified that participants did not have any skin condition, allergies, skin type, or any other physical condition that may interfere with the types of measurements being made in the study. Any excess hair was trimmed when necessary. Eight test sites were outlined on the bilateral volar forearms (4 per side) of each participant using a standard template. This allowed for intraparticipant comparison of the products. A clean cotton swab was dipped into the activated carbon, tapped to remove excess, and used to apply in a thin layer to a 0.75-in diameter area within the test site. Each tested product was applied to a different test site on each arm according to a randomization schedule. The application was done using a pipette to deposit 4 to 5 drops of the product and using the pipette tip to spread the product across the site. All products were allowed to dry for about 5 minutes before digital imaging. Participants were reminded to shower and wash their arms as usual during the study period.

Digital imaging

Digital photographs were taken of each test site at day 0 prior to carbon application (baseline) and after the products were applied and dried over the carbon, as well as at days 1, 2, 3, 4, and 7. The photographs were evaluated to determine the amount of activated carbon remaining using Image Pro Premiere 9.0 software (Media Cybernetics, Rockville, MD) to obtain a carbon integrated optical density (CIOD) value. In this method, a brighter/whiter image produces a higher CIOD value and pure black producing a value of zero. The investigator (TH) taking and analyzing the photos was blinded to the treatment code and randomization schedule.

Statistical methods

Statistical analyses were performed using GraphPad InStat Software (GraphPad Software, La Jolla, CA). The results were normalized based on the bare skin reading obtained with the baseline measurement according to the equation (Formula).

A repeated measures analysis of variance with a first-order autoregressive covariance matrix and a Bonferroni adjustment for multiple comparisons were used to compare the CIOD values and the calculated percent barrier remaining values within and between treatments over time. For all analyses, a 2-tailed P ≤ .05 was used as the level of significance.

Twenty-one healthy volunteers were enrolled in this clinical study in November 2016 (age range, 28–69 years). Four commercial products were tested in duplicate on their bilateral forearms and durability was assessed using image analysis to quantify the amount of active carbon remaining under the tested products over time as a surrogate measure for how much product was left. Figure 1 illustrates an example of 1 participant's arm at all time points, showing differences in wear pattern between the products over time. Code A showed no appreciable wear over the 7 days. Code B began peeling away in flakes as early as day 2, and code C was progressively lost from the skin surface in much smaller flakes. Code D partially detached and folded over onto itself until it was completely gone by day 3.

Figure 2 shows the CIOD values (mean and standard error) for all products at the various time points. The CIOD values for all 4 tested products decreased compared with the baseline values (skin only) due to the presence of the black carbon particles. As the products wore off, so did the carbon particles that were no longer protected, causing the skin to become lighter and the CIOD values to increase over time. Confirming the observations reported in Figure 1, there were differences in the skin persistence patterns of the 4 tested products.

Carbon integrated optical density values within treatments

For code A, no significant changes in CIOD values were observed over time (P = .46), indicating the film persisted throughout the study. For codes B and D, the CIOD values at days 3, 4, and 7 were significantly higher (P < .01) than for day 1. This indicates that by day 3, there was a significant reduction in the amount of product left on the skin compared with the amount originally applied. For code C, the CIOD values at days 4 and 7 were significantly higher (P < .01) than for day 1.

Carbon integrated optical density values between treatments

The CIOD values for code A were significantly lower than those for code B at days 2 (P = .0009), 3 (P = .0001), 4 (P = .0001), and 7 (P = .0001); significantly lower than those for code C at days 2 (P = .0037), 3 (P = .0001), 4 (P = .0001), and 7 (P = .0001); and significantly lower than those for code D at days 3 (P = .0001), 4 (P = .0001), and 7 (P = .0001).

The raw CIOD values were used to calculate the percent barrier remaining for each participant and product per the equation given above. Figure 3 displays the mean percent of product remaining over time (with standard errors). These curves show that code A remained on the skin throughout the 7-day study period, whereas codes B, C, and D declined steadily throughout the study, with < 50% left on the skin by day 7.

Percent barrier within treatments

For code A, no significant changes in percent barrier remaining were observed over time (P > .99). For codes B and C, the percent barrier remaining at days 4 and 7 was significantly lower than for day 1 (P < .01). For code D, the percent barrier remaining at days 3, 4, and 7 was significantly lower than for day 1 (P < .01).

Percent barrier between treatments

Code A had significantly greater percent barrier remaining than code B at days 2 (P = .0006), 3 (P = .0001), 4 (P = .0001), and 7 (P = .0001). Code A had significantly greater percent barrier remaining than code C at days 1 (P = .01), 2 (P = .0012), 3 (P = .0001), 4 (P = .0001), and 7 (P = .0001). Code A had significantly greater percent barrier remaining than code D at days 3 (P = .0001), 4 (P = .0001), and 7 (P = .0001).

There was no skin irritation (erythema or edema) observed during this study, and no adverse events were observed or reported for any of the codes.

In the present model using the assessment of pigment retention on the forearms of healthy volunteers, code A was more durable than codes B, C, and D. Code A showed no significant change from day 1 through day 7, indicating that the film did not show any significant wear. Codes B and D showed significant increases in CIOD beginning at day 3 (P < .01), remaining so through day 7. Code C showed no significant difference at day 2 or 3 but highly significant increases in CIOD for days 4 and 7 (P < .01).

Code A outperformed all other products, showing on average no significant wear by day 7, whereas the codes B, C, and D had < 50% remaining on the skin by that time point. The percent barrier remaining for code A was significantly greater than code B (P < .001) from day 2 onwards, significantly greater than code C (P ≤ .01) from day 1 onwards, and significantly greater than code D (P ≤ .023) from day 3 onwards.

Best practices in preventing and managing IAD consist of cleansing the skin at least once daily and after each episode of fecal incontinence and using a skin care product or combination product with skin protective/restorative actions.¹⁴ It is generally agreed that further research is needed to assess the comparative effectiveness of different products and skin care regimens in this arena. At this point, there is insufficient evidence to recommend any specific product for use in a standardized skin care protocol for IAD.¹⁷ The particularly unique advantage of this skin protectant product (code A) relies in its ability to adhere to denuded skin, as demonstrated in clinical use,¹⁶ while providing a smooth protective surface that is easy to clean and more durable than standard barrier films. Code A successfully forms a protective layer so the skin can be cleansed without removing the film, even in cases of severe fecal incontinence, making the process much easier for the clinician and much less painful for the patient when compared with pastes. It also does not need to be reapplied after each cleansing because it does not wash off readily. This product has the potential to greatly improve the care of patients with severe incontinence, including fecal incontinence such as observed with Clostridium difficile infections. Further, the product does not require removal, as it will wear off the skin over time, but if removal is desired, it can be done with a silicone-based skin adhesive remover.

The study model presented herein allows for simultaneous comparison of several products, which is currently lacking in this field where most comparative studies evaluate 2 or 3 products. There are published methods^18,19 based on the colorimetric measurement of a harmless marker dye such as methyl violet. Such methods can be used as either a dye retention or a dye exclusion test. In a dye retention test,¹⁸ the skin site is first colored with dye and then covered with a putative skin protectant. By monitoring the disappearance of the underlying marker dye over time, one can determine how long the protective film has remained in place. The major drawback is that it may take some time for the dye to fade from the newly exposed skin, causing the duration of protection to be overestimated. In a dye exclusion test,¹⁹ the skin protectant is applied first and its efficacy is evaluated by its ability to prevent the dye from reaching the skin. With this, the major drawback occurs when the dye is picked up by the skin protectant, in which case the film must be removed to assess whether the skin has been dyed or not, eliminating the possibility of monitoring the same site over time.

The improved method reported herein uses the color retention approach but utilizes activated carbon powder as the reference marker rather than a water-soluble dye. Since this powder consists of fine, dark particles that will not chemically react with the skin and are virtually insoluble in water, oil, or typical solvents, it is ideal for this application. When brushed on the skin, the powder will adhere to the test site but can be easily removed by rinsing with water. The basic principle of this improved test is that an efficacious skin protectant should provide a physical barrier between the powder and the activities of daily wear (eg, rub-off and showering). The amount of pigment retention over time can be easily monitored, and this approach also will reveal the pattern of how the protectant fails over time (eg, uniform fading versus flaking off).

This method has been presented previously at medical conferences^20,21 and is published here for the first time. There is no doubt that a number of variations in this test method could be developed to create additional models; such methods can provide useful tools to screen large numbers of formulations before proceeding with comparative clinical studies and offer the advantage of having several products compared on the same subject, alleviating the effects of subject-to-subject variation.

The study presented herein has some limitations. It uses an experimental model of protecting a circle of pigment on healthy skin with products intended to manage IAD to evaluate the durability of the products over time. Participants likely showered only once daily (as opposed to the multiple cleansings necessary in patients with several incontinence episodes per day). Their skin was not exposed to harsh body fluids. Nevertheless, all compared products experienced the same conditions, and code A comparatively displayed superior durability, which should carry over in a clinical setting, even if the overall durability is different under clinical conditions relevant to IAD.

This study represents one of the methods used to characterize the study product (code A); other methods were published in separate studies and included an animal model (showing that this skin protectant protects intact and denuded skin from irritants and provides an environment favorable to healing),¹⁵ a bench microbiology method (verifying that it does not support in vitro microbial growth of organisms relevant for IAD),²² and another human volunteer study looking at skin temperature upon application (demonstrating that it mitigates the typical rise in temperature seen with cyanoacrylates and may be more comfortable for IAD patients).²³ In addition, the product was tested in a clinical study on 16 patients and was shown to reduce the IAD score and the pain score.¹⁶

The code A skin protectant product (new investigational formulation) shows promise for the prevention and management of IAD and warrants further testing in larger clinical studies. It appears more durable than the other products indicated for the same purpose tested in this study.

The authors thank the study personnel at cyberDERM (Broomall, PA) for protocol implementation.

Affiliations: 3M, St Paul, MN; and cyberDERM, Inc, Broomall, PA

Correspondence: Stéphanie F. Bernatchez, PhD, 3M Center Building 270-3A-04, St Paul, MN 55144-1000; sfbernatchez@mmm.com

Disclosure: This study was performed at cyberDERM (Broomall, PA) and funded by 3M (St Paul, MN). Mary Mathisen and Stéphanie Bernatchez are employees of 3M. Tim Houser and Gary Grove are employees of cyberDERM. All authors were involved in the study design, acquisition of data and literature, and analysis and interpretation of data, as well as in the preparation of the intellectual content of this manuscript. No ghost writer was used to prepare this manuscript. Since the original submission of this article, the investigational product described in this manuscript has received US Food and Drug Administration approval and is now commercially available under the name 3M Cavilon Advanced Skin Protectant (3M).