Superiority of a Novel Multifunctional Amorphous Hydrogel Containing Olea europaea Leaf Extract (EHO-85) for the Treatment of Skin Ulcers: A Randomized, Active-Controlled Clinical Trial

Abstract

This 8-week, multicenter, randomized, active-controlled, observer-blinded clinical trial was designed to demonstrate the accelerating effect on wound healing of the novel Olea europaea leaf extract hydrogel (EHO-85) by comparing it to a widely used amorphous hydrogel. Results showed that EHO-85 significantly accelerated wound healing, regardless of ulcer etiology (pressure, venous leg or diabetic foot) and prognosis, doubling the median wound area reduction compared with a reference amorphous hydrogel (79.4% vs. 39.7%; difference: −39.7%, 95% CI: −71.1 to −21.3%; p < 0.001). The intention-to-treat analysis was conducted on 195 patients from 23 Spanish health centers/nursing homes. This novel treatment balances the ulcer microenvironment by modulating reactive oxygen species and pH. These actions complement the moistening and barrier functions inherent to amorphous hydrogels, whilst also conferring EHO-85 its documented granulation formation and pain relief properties. Furthermore, efficacy was achieved safely and in a cost-efficient manner due to its multi-dose format, which reduced the amount of product needed by 85.8% over 8 weeks compared to single-use hydrogel. The present randomized controlled trial is a relevant milestone in evidence-based practice for being the first to demonstrate (i) the effectiveness of an amorphous hydrogel in accelerating wound healing and (ii) the superiority of a specific hydrogel over another.

Biological effects of the olive tree and its derivatives on the skin

“…Regardless of their aetiology, a greater number of patients achieved good results after application of the extracts in hydrogel form, with a significant reduction in the wound area and an acceleration of the healing process compared to that of the control. 128,129…”

“…127 Olea europaea leaf extract hydrogel (EHO- 85) In vivo (human subjects/both sexes): this clinical trial observed that EHO-85 accelerated wound healing regardless of ulcer etiology by modulating reactive oxygen species and pH. 128…”

“…Regardless of their aetiology, a greater number of patients achieved good results after application of the extracts in hydrogel form, with a significant reduction in the wound area and an acceleration of the healing process compared to that of the control. 128,129 The benefits of olive oil and its derivatives are not only limited to the treatment of chronic wounds, but have also been used to treat other skin conditions such as burns. In this regard, Bayir et al 130 evaluated the combined therapy of bandages impregnated with beeswax, olive oil and butter in a rat model of second-degree burns.…”

Guidelines on interventions to enhance healing of foot ulcers in people with diabetes (IWGDF 2023 update)

“…Further, reduction in ulcer area was reported in six studies 72,74,75,77,79,80 of which only two 72,77 found an apparent improvement in comparison to the control. Again, these were at high risk of bias.…”

“…Rationale: We found nine RCTs which reported on the use of topica herbal or traditional medicinal preparations, which fulfiled our inclusion criteria. [72][73][74][75][76][77][78][79][80] Of seven studies reporting on complete wound healing, [72][73][74][75][76][77]79 all were at moderate or high risk of bias, and any positive effects on wound healing should be interpreted cautiously.…”