RCT to evaluate a hyaluronic acid containing gauze pad in leg ulcers of venous or mixed aetiology

Abstract

This study was sponsored by Laboratoires Genévrier. Authors received honoraria for their contributions to the study, but have no other conflicts of interests to declare.

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

“…In case non-inferiority could be documented, in order to demonstrate superiority of the EHO-85 gel, given the previously estimated sample, the Clinical Investigation Plan considered that assuming an α risk fixed at 0.05, it would be necessary to obtain a difference on the WAR of both groups of at least 15% at the end of the study to achieve a power of 80%, assuming normality. This difference was in line with that described to document WAR superiority in prior clinical trials [ 6 , 23 , 24 ]. To avoid bias due to multiple comparisons, since the assessment of non-inferiority and potential superiority was assessed on overlapping and non-independent populations, a Bonferroni correction was performed, reducing the effective α threshold in the test.…”

“…The difference in median WAR between hydrogels was almost 40% in favor of EHO-85, which represents a 2-fold increase in the WAR rate. It is far better than the 15% proposed as being clinically relevant in the literature [6,23]. Other secondary endpoints designed to document whether EHO-85 accelerates the healing process of skin ulcerssuch as absolute WAR and daily healing rate-reinforced that hypothesis.…”

“…The main efficacy criterion in our study was the decrease in the wound area from baseline or relative WAR. Change in the ulcer area after 8 weeks of therapy is considered a surrogate marker to predict healing of chronic wounds [ 29 , 30 ] and it has been used increasingly in clinical trials of skin ulcer therapy [ 6 , 23 , 31 ]. Despite the fact that the study was open, this criterion was evaluated centrally and blindly by an independent researcher and the statistical analysis was conducted by an independent entity.…”

“…With regard to this point, the main limitation of the study was the follow-up duration. According to previous studies [ 6 , 23 ], 8 weeks might not be a long enough period to detect statistically significant differences in the percentage of patients with complete (100%) healing. As we observed significant differences in the number of patients with WAR ≥ 80%, we would probably have found statistically significant differences with a longer follow-up of 10 or 12 weeks.…”

“…Such reduction in wound area within the first weeks of treatment is highly predictive of a fully healed ulcer within 20–24 weeks [ 29 , 32 , 33 , 34 , 35 ]. Accordingly, the percentage of patients achieving WAR ≥ 40% after 56 days has been used as an endpoint in recent RCTs on wound healing [ 6 , 23 ].…”