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.

José Verdú-Soriano,Caridad Dios-Guerra,Paloma Moreno-Moreno,José Luis Lázaro-Martínez,Ipek Guler-Caamaño,Leocadio Rodríguez-Mañas,Javier Caballero-Villarraso,Marisol De Cristino-Espinar,Miriam Berenguer-Pérez,Silvia Luna-Morales,Olga Laosa-Zafra,Antonio Casado-Díaz

doi:10.3390/jcm11051260

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.

Highlights

Chronic wounds are of increasing frequency globally because of ageing populations and the rising prevalence of obesity, diabetes, and vascular disease [1]
The new EHO-85 gel was designed to be capable of combining the moistening and barrier-function properties of any amorphous hydrogel with the novel ability to downregulate reactive oxygen species (ROS) and pH, modulating the microenvironment of the ulcer in a holistic manner
The main efficacy criterion in our study was the decrease in the wound area from baseline or relative Wound Area Reduction (WAR)

Summary

Introduction

Chronic wounds are of increasing frequency globally because of ageing populations and the rising prevalence of obesity, diabetes, and vascular disease [1]. It has been estimated that in a population of 1 million people, 3500 people would have a chronic wound or skin ulcer, of which 525 would have a lesion with an evolution >12 months [2]. Those injuries represent an important burden for patients and society in terms of quality of life, resource consumption, and direct and indirect costs [2,3]. Patients with chronic wounds have increased morbidity [4], and their mortality risk is higher than that of the general population, independent of age, sex, and ulcer etiology [3]. Despite its potential for wound healing promotion [6,7], little attention has been paid to modulation of the ulcer microenvironment, wound-bed preparation is considered an essential step towards healing [8]

Methods

Results

Conclusion