Protease-modulating polyacrylate-based hydrogel stimulates wound bed preparation in venous leg ulcers--a randomized controlled trial

Abstract

Background: Stringent control of proteolytic activity represents a major therapeutic approach for wound-bed preparation.

Objectives: We tested whether a protease-modulating polyacrylate- (PA-) containing hydrogel resulted in a more efficient wound-bed preparation of venous leg ulcers when compared to an amorphous hydrogel without known protease-modulating properties.

Methods: Patients were randomized to the polyacrylate-based hydrogel (n = 34) or to an amorphous hydrogel (n = 41). Wound beds were evaluated by three blinded experts using photographs taken on days 0, 7 and 14.

Results: After 14 days of treatment there was an absolute decrease in fibrin and necrotic tissue of 37.6 ± 29.9 percentage points in the PA-based hydrogel group and by 16.8 ± 23.0 percentage points in the amorphous hydrogel group. The absolute increase in the proportion of ulcer area covered by granulation tissue was 36.0 ± 27.4 percentage points in the PA-based hydrogel group and 14.5 ± 22.0 percentage points in the control group. The differences between the groups were significant (decrease in fibrin and necrotic tissue P = 0.004 and increase in granulation tissue P = 0.0005, respectively).

Conclusion: In particular, long-standing wounds profited from the treatment with the PA-based hydrogel. These data suggest that PA-based hydrogel dressings can stimulate normalization of the wound environment, particularly in hard-to-heal ulcers.

Figure 1

Flow diagram of the patients involved in the study. The results shown in the present report were based on the ITT-population.

Figure 2

At day 0 the wound was 90% covered with fibrin and necrotic tissue related to the total wound area (= 100%). At day 14, the proportion of fibrin and necrotic tissue was reduced to 8% of the total wound area. This decrease (90%–8%) corresponds to a difference of 82 percentage points (synonymic with the term ‘absolute reduction’ used in the present report). This difference is equivalent to a percent reduction in fibrin and necrotic tissue of 91.1% related to the proportion of 90% fibrin and necrotic tissue on day 0.

Figure 3

Absolute decrease in fibrin and necrotic tissue (a). Cumulative distribution of the absolute change in the amount of fibrin and necrotic tissue at day 14 after treatment with either the PA-based hydrogel or the amorphous hydrogel (b). The graph representing the wounds treated with PA-based hydrogel is clearly shifted to the left compared to the graph representing wounds treated with the amorphous hydrogel. Each point represents one wound.

Figure 4

Absolute increase in granulation tissue (a). Cumulative distribution of the absolute change in the amount of granulation tissue at day14 after treatment with either the PA-based hydrogel or the amorphous hydrogel (b). The graph representing the wounds treated with PA-based hydrogel is clearly shifted to the right. Each point represents one wound.

Figure 5

Odds ratio for the possibility of having <50% fibrin and necrotic tissue or having >50% granulation tissue after 14 days of treatment with either the PA-based hydrogel or the amorphous hydrogel compared to each other.

Figure 6

Distribution of ulcers related to the coverage with fibrin and necrotic tissue and to ulcer duration (a). In the PA-based hydrogel group, none of the hard-to-heal ulcers (>6 months duration) had <50% surface coverage with fibrin and necrotic tissue at day 0. After 14 days, the proportion of fibrin and necrotic tissue had decreased to <50% of the wound surface in 12 of 22 wounds. In the amorphous hydrogel group, 2 of 30 wounds had <50% surface coverage with fibrin and necrotic tissue at day 0. After 14 days, 7 of 30 wounds were covered with <50% fibrin and necrotic tissue. Distribution of ulcers related to the coverage with granulation tissue and to the duration (b). In the PA-based hydrogel group, none of the hard-to-heal ulcers (>6 months duration) had >50% surface coverage with granulation tissue at day 0. After 14 days, in 11 of 22 wounds the proportion of granulation tissue had increased to >50%. In the amorphous hydrogel group, 2 of 30 wounds had >50% surface coverage with granulation tissue at day 0. After 14 days, the number increased to 6 of 30 wounds.