Evaluation of a Novel Wound Closure Device: A Multicenter Randomized Controlled Trial

Abstract

ACADEMIC EMERGENCY MEDICINE 2011; 18:1060–1064 © 2011 by the Society for Academic Emergency Medicine

Abstract

Objectives:  A novel wound closure device combining a mesh tape and octylcyanoacrylate (OCA) topical skin adhesive (TSA) was developed to facilitate wound closure and enhance the adhesive’s strength. The objective of this study was to determine whether the incidence of wound dehiscence after laceration repair with the new device was equivalent to that after use of a high-viscosity OCA. We hypothesized that the rate of complete wound edge apposition would be equivalent for the two closure devices.

Methods:  This was a multicenter, randomized clinical trial in nine academic and community emergency departments (EDs) and urgent care centers. Patients with simple traumatic lacerations were included. Lacerations were randomly closed with a high-viscosity OCA or mesh tape–OCA combination. The rate of complete wound edge apposition at 14 days, rates of wound infection at 14 and 30 days, and the percentage of optimally appearing scars at 30 days after closure were assessed. Assuming a maximal clinically acceptable difference for equivalence of 8% in the rate of completely apposed wound edges, a sample of at least 138 patients in the tape–OCA group and at least 69 in the OCA-only group would give 80% power and a one-sided significance level of 5%.

Results:  During the study period the investigators enrolled 216 subjects, of whom 143 were randomized to the tape–OCA combination and 73 to the OCA-only group. Most wounds were located on the face and the upper extremities. Mean laceration length was similar in patients in both groups (tape–OCA 2.1 cm vs. OCA-only 2.0 cm; difference 0.1 cm, 95% confidence interval [CI] = −0.45 to 0.58 cm). The rate of complete wound edge apposition at 14 days was higher in wounds treated with the tape–OCA combination than in wounds treated with OCA alone (86.0% vs. 78.1%). The upper bound of the one-sided CI was 1.0% for the intention-to-treat population, which was less than the predetermined acceptable difference of less than 8%. There were no between-group differences in rates of infection and optimally appearing scars.

Conclusions:  When compared with OCA alone, the novel tape–OCA combination is equivalent with regard to complete wound edge apposition and cosmetic appearance.

Topical skin adhesives (TSAs) have been used for wound closure for several decades.¹ Despite their availability, the use of TSAs has been mostly limited to short, low-tension wounds, especially in children and on the face.² In an effort to facilitate the closure of long wounds, a new closure device that combines a 2-octyl-cyanoacrylate (OCA)-based TSA applied on top of a mesh tape containing a chemical initiator has been developed. The tape–OCA combination offers several advantages over current TSA formulations. Since the tape is used to temporarily approximate the wound edges, this combination is more convenient for practitioners. Because manual apposition of the wound edges is no longer required, it allows closure of long wounds without the need for additional assistance to hold the entire wound edges together while the TSA is applied and polymerizes. Since the TSA does not polymerize until coming into contact with the mesh tape, it also gives the practitioner longer working time. The tape–OCA combination was also designed to polymerize more rapidly than the OCA alone. A study in animals demonstrated that a combination of tape and OCA is stronger than either device alone.³ As a result, only a single layer of the adhesive is required, further shortening the time required for wound closure.

The objective of this study was to determine whether the incidence of wound dehiscence after laceration repair with the new polyester mesh tape–OCA combination was equivalent to that of a high-viscosity OCA. We hypothesized that the rate of wound dehiscence would be equivalent for the two closure devices.

Methods

Study Design

An open-label, multicenter, randomized, controlled trial study design was used to test the study hypothesis. The study was approved by the institutional review boards of the participating centers.

Study Setting and Population

The study was conducted at nine academic and community emergency departments (EDs) and urgent care centers. All study providers were attending emergency physicians with prior experience using TSAs.

Patients with traumatic lacerations were eligible for enrollment if they were age 1 year or greater, were in good general health, were willing to follow instructions for wound care, and agreed to return for follow-up evaluation. Patients with significant multiple trauma or peripheral vascular disease or those receiving antibiotics, with a clotting disorder, known to be immunocompromised (including HIV), taking systemic steroids, with a history of keloids or hypertrophic scars, and with known allergy to cyanoacrylate, formaldehyde, tapes, or adhesives were excluded. The following wounds were excluded: stellate wounds, bites, punctures, wounds in the presence of devitalized or contaminated tissue, wounds over mucosa or mucocutaneous borders, wounds over hair-bearing areas, and those subject to high skin tension (such as knees, elbows, and knuckles).

Study Protocol

Wound Closure Devices.  Dermabond Protape (Ethicon Inc., Somerville, NJ) is composed of a 2-OCA TSA and a polyester mesh substrate, which together, when applied to the skin, act as a topical wound closure device (Figure 1). The mesh component is used to maintain approximation of the wound edges on a temporary basis prior to application of the liquid adhesive. Once the adhesive is applied over the mesh, polymerization occurs, resulting in wound closure. The comparator wound closure device was the commercially available high-viscosity Dermabond (Ethicon Inc., Somerville, NJ) TSA composed of liquid 2-OCA, which is applied to the manually approximated wound edges in two layers. With this formulation, the initiator of the polymerization process is contained within the tip of the applicator. With the tape–OCA combination, the initiator is located within the tape itself.

Figure 1.  Facial laceration (left) closed with application of TSA over mesh tape (right). TSA = topical skin adhesive.

Wound Closure.  If required, the deep tissues were closed with interrupted deep dermal sutures. Hemostasis was achieved using direct pressure, and wound closure was randomized by opening the next of consecutively numbered opaque envelopes that contained the wound closure assignments. Patients were assigned to either the tape–OCA combination, or the OCA alone, in a 2:1 allocation ratio as requested in consultation with the Food and Drug Administration. Treatment allocation was stratified by study site. If the patient had more than one laceration, all eligible wounds were randomized according to the same one-patient randomization envelope. After wound closure was complete, a dry, nonmedicated wound dressing could be applied; however, use of additional dressings was not required.

Structured data collection was performed using standardized forms. Information collected included patient demographics, clinical history, and wound characteristics (e.g., dimensions, location). Details regarding device function were also collected, and the number of devices used was recorded.

At 14 (±2) days following wound closure, any remaining tape was removed and the wound was assessed. If healing of the wound was not yet sufficient to allow removal, an additional follow-up visit was scheduled. The presence of any remaining wound closure device was recorded as none present, visible but providing no closure support, intact and providing intermittent closure support to the wound, or fully intact supporting closure of the entire wound. Any remaining adhesive was removed by peeling it away. Removal of the adhesive could be facilitated by petrolatum jelly or acetone. The degree of wound edge apposition was determined as either complete with no dehiscence or incomplete with dehiscence or need for reclosure. The presence of inflammation was also determined for each of the following elements: erythema, edema, pain, and temperature. A wound was considered infected in the presence of redness more than 3–5 mm from the repaired wound, swelling, purulent discharge, pain, increased skin temperature, fever, or other systemic signs of infection. Wounds were only considered infected when signs of infection were present and when a health care provider prescribed systemic antibiotics to treat the infection.⁴ The presence of skin blistering or any other adverse events was also noted.

At 30 (standard deviation [SD] ±5) days following wound closure, the cosmetic appearance of the wound was assessed by an investigator masked to device assignment using a previously validated six-item ordinal wound evaluation scale that included the absence (1 point each) or the presence (0 points each) of a wound step-off of borders, contour irregularities, wound margin separation, edge inversion, excessive inflammation, and overall poor appearance.⁴ An overall cosmesis score was calculated by adding the individual scores on each of the items. A total score of 6 was considered an optimal outcome. Any score below 6 was considered suboptimal.

Measures

The primary outcome was the incidence of complete wound edge apposition at 14 days after laceration repair without dehiscence or the need for reapproximation. Secondary outcomes were the incidence of wound infection at 14 and 30 days and the percentage of lacerations with an optimal cosmesis score at 30 days after repair.

Data Analysis

Continuous variables are presented as means and SD and compared with parametric or nonparametric tests as appropriate. Binary data are presented as the percentage frequency of occurrence and compared with the chi-square or Fisher’s exact tests. All analyses were based on the intention-to-treat principle. Statistical analyses were performed using SAS v9.1.3 (SAS Institute, Cary, NC).

Sample Size Calculation.  A prior study demonstrated complete wound apposition in 97.2% of wounds closed with the OCA comparator.⁵ Assuming a 95% complete wound apposition rate in lacerations closed with OCA alone, and a maximal clinically acceptable difference for equivalence of 8% in wound dehiscence rate, a sample of at least 138 patients in the tape–OCA group and at least 69 in the OCA-only group would give 80% power and a one-sided significance level of 5%. To adjust for a 5% drop-out rate, 216 patients (114 in the tape–OCA group and 72 in the OCA-only group) were enrolled in the study.

Results

General Characteristics

During the study period, 216 subjects were enrolled, of whom 143 (91 men and 52 women) were randomized to the tape–OCA combination and 73 (47 men and 26 women) to the OCA-only group. Of these, 204 patients had one eligible wound, seven had two eligible wounds, and two had three eligible wounds. Three of the 216 randomized patients (one in the tape–OCA group, two in the OCA-only group) were not treated. The mean age of those treated with the tape–OCA combination was 25.0 years (SD ±18.4 years, median 24.0 years), and of those treated with OCA alone was 25.7 years (SD ± 19.8 years, median = 21.0 years). The majority of the study patients were white (Table 1). Most wounds were located on the face and the upper extremities. Mean laceration length was similar in patients treated with the tape–OCA combination and OCA alone (2.1 cm vs. 2.0 cm; difference 0.1, 95% confidence interval [CI] = −0.45 to 0.58 cm). Deep sutures were used in 26 patients in the tape–OCA combination group and in 14 patients in the OCA-only group (p = 0.86).

Table 1.    Demographic Characteristics*

Characteristic	Tape–OCA Combination (n = 143)	OCA Alone (n = 73)
*None of the differences between the groups were statistically significant OCA = octylcyanoacrylate.
Age (yr), mean (±SD)	25.0 (±18.4)	25.7 (±19.8)
Females, n (%)	52 (36.4)	26 (36.5)
Race, n (%)
White	97 (67.8)	51 (69.9)
Black or African American	36 (25.2)	20 (27.4)
Other	10 (7.0)	2 (2.7)
Ethnicity, n (%)
Hispanic	12 (8.4)	10 (13.7)
Non-Hispanic	131 (91.6)	63 (86.3)
Laceration length (cm), mean (±SD)	2.0 (±1.6)	2.1 (±2.3)
Laceration length (cm), median (range)	1.5 (0.2–14.0)	1.5 (0.2–14.0)
Laceration location, n (%)
Face	83 (56.8)	53 (67.9)
Upper extremity	54 (37.0)	21 (26.9)
Lower extremity	8 (5.5)	2 (2.6)
Trunk	1 (0.7)	2 (2.6)
Deep sutures, n (%)	26 (18)	14 (19)

Primary Outcome

The rate of complete wound edge apposition at 14 days was higher in wounds treated with the tape–OCA combination than in wounds treated with OCA alone (86.0% vs. 78.1%). The upper bound of the one-sided CI was 1.0% for the intention-to-treat population, which was less than the predetermined acceptable difference of less than 8% between the wounds closed with the tape–OCA combination and the OCA alone (Table 2).

Table 2.    Outcomes

Outcome	Tape–OCA (n = 143)	OCA (n = 73)	Difference	Exact 90% CI
AIRE = acute inflammation, redness, and edema scale; OCA = octylcyanoacrylate.
Complete wound edge apposition, n (%)	123 (86.0)	57 (78.1)	−7.9	−17.7 to 1.0
Incomplete wound edge apposition, n (%)	20 (14.0)	16 (21.9)
Cosmesis score, n (%)			p-value by Fisher’s exact test
Optimal total score (6)	93 (65.0)	43 (58.9)	p = 0.457
Step off of borders	30 (21.0)	19 (26.0)
Contour irregularities	42 (29.4)	24 (32.9)
Wound margin separation	37 (25.9)	20 (27.4)
Wound edge eversion	33 (23.1)	20 (27.4)
Excessive inflammation	27 (18.9)	18 (24.7)
Poor overall appearance	34 (23.8)	22 (30.1)
Inflammation score, Day 14, n (%)
Optimal score (0)	89 (62.2)	38 (52.1)	p = 0.188
Presence of any erythema	43 (30.1)	30 (41.1)
Presence of any edema	26 (18.2)	23 (31.5)
Presence of any pain	30 (21.0)	22 (30.1)
Presence of any warmth	20 (13.9)	15 (20.5)
AIRE score, Day 30, n (%)
Optimal score	88 (61.5)	44 (60.3)	p = 0.883
Presence of any erythema	48 (33.6)	26 (35.6)
Presence of any edema	36 (25.2)	19 (26.0)
Presence of any pain	33 (23.1)	18 (24.7)
Presence of any warmth	26 (18.2)	16 (21.9)
Wound infection
Day 14	4 (3.2)	1 (1.7)
Day 30	2 (1.7)	0 (0.0)

Secondary Outcomes

A summary of the total and individual inflammation scores is presented in Table 2. On Days 14 and 30 after laceration repair, the rates of wounds with other than normal scores were similar between the two groups. The rate of wounds with an optimal cosmetic outcome at 30 days in the tape–OCA combination groups was also similar to that in the OCA-only group (65.0% vs. 58.9%; p = 0.46). A breakdown of individual scores on the ordinal cosmesis scale is presented in Table 2.

Adverse Events

There were four wound infections on Day 14; three were in the tape–OCA group, and one was in the OCA-only group. On Day 30 there were two infections in the tape–OCA group and none in the OCA-only group. Only one patient in the OCA-only group developed wound dehiscence requiring repeat wound closure; there were no cases of wound dehiscence requiring reapproximation in the tape–OCA group. There was one patient in the tape–OCA group who developed a blister at the site of the wound.

Discussion

The results of this study demonstrate that the tape–OCA combination and the OCA alone are equivalent with regard to both cosmetic outcome and need for reclosure due to wound dehiscence. Whether analyzed by intention-to-treat or per-protocol, the rates of wound dehiscence at 14 days were similar between groups, as were the rates of optimally appearing scars at 30 days. Due to small sample size and the small number of wound infections, it is not possible to conclude that infection rates were also similar.

While TSAs are used millions of times per year for a wide range of traumatic lacerations and surgical incisions, their use is mostly limited to short facial wounds in children.² Based on a survey conducted at one of the study institutions, one of the reasons for this is the practitioner’s perceived lack of confidence in the strength of TSA (unpublished data). Another reason why TSAs have been limited to shorter lacerations is the technical difficulty associated with closing long wounds. Both of these potential barriers are minimized with the use of the new OCA-tape combination. A prior study in animals has shown that the bursting strength of wounds closed with TSA on top of tape is considerably higher than that of either TSA or tapes alone.³ In our practice, we have found that application of tape across the wound allows approximation of any length of wounds without the need for additional hands to appose the wound’s edges while applying the TSA. Another obvious advantage of the tape–OCA combination is that due to its enhanced strength, only one layer of adhesive is required, shortening the overall process of wound repair. A prior formulation of high-viscosity OCA has required application of two layers.⁵ Finally, since the chemical initiator of the polymerization process is no longer part of the TSA vial, there is no urgency to use all of the adhesive immediately after opening the vial. This is especially advantageous when closing multiple traumatic lacerations or surgical incisions in the same patient.

Limitations

The mean length of lacerations in the current study was relatively short, making it difficult to generalize the results to longer lacerations. However, a prior study using an OCA-based TSA alone in patients with surgical incisions greater than 4 cm (mean length of approximately 16 cm) has demonstrated that the OCA can be used in long wounds with very good outcomes that are comparable to sutures.⁶ Second, our study was limited to traumatic lacerations repaired in the ED. However, prior studies have found that both lacerations and surgical incisions repaired with TSA have similar outcomes to sutured wounds.⁷ Third, most wounds in our study were on the face and the upper extremities, limiting generalization to other body areas and locations. Fourth, due to the small number of wound infections, we could not definitively conclude that infection rates were similar between the groups. Finally, it was not possible to mask the providers who closed the wounds to the closure device. However, this potential bias was limited by having the wound evaluations performed by personnel masked to study assignment after removal of the device.

Conclusions

This study evaluated wound outcomes of traumatic lacerations closed with a novel octylcyanoacrylate topical skin adhesive mesh tape combination. When compared with octylcyanoacrylate alone, the tape–octylcyanoacrylate combination is equivalent with regard to complete wound edge apposition and need for reclosure due to wound dehiscence, as well as cosmetic appearance.