Focused shockwave therapy in diabetic foot ulcers: secondary endpoints of two multicentre randomised controlled trials

Abstract

Objective: The objective of this paper is to present the secondary safety and efficacy outcomes from two studies of focused extracorporeal shockwave therapy (ESWT) used adjunctively with standard care in the treatment of neuropathic diabetic foot ulcers (DFU) (1A or 2A on the University of Texas grading scheme), compared with sham treatment and standard care. Method: We carried out two multicentre, multinational, randomised, sham-controlled, double-blinded, phase III clinical studies using standard care with adjunctive focused ESWT compared with sham treatment and standard care in patients with a DFU. DFUs that did not reduce in volume by at least 50% over two weeks' standard treatment were included. DFUs were randomised and managed with standard care and focused ESWT (pulsed acoustic cellular expression; dermaPACE System, SANUWAVE Health, Inc.) active therapy, or with standard care and sham treatment, four times over a two-week treatment phase in study 1 and up to eight times over 12 weeks in study 2. Standard care continued in both studies throughout the 12-week treatment phase. Secondary outcomes were indicators of wound closure and progression, pain, infection, amputation and recurrence, and device reliability. Efficacy-related secondary endpoints were measured at 12, 20 and 24 weeks. The studies were analysed separately and following statistical comparison to justify the method, as a pooled data set. Results: Wound area reduction (48.6% versus 10.7%, p=0.015, intention to treat (ITT) population with last observation carried forward (LOCF)) and perimeter reduction (46.4% versus 25.0%, p=0.022, ITT population with LOCF) were significantly greater in the active therapy group compared with the sham-treated group, respectively. The difference in time to wound closure in the pooled ITT population was significantly in favour of the active therapy group (84 days versus 112 days for 25% of subjects to reach wound closure in the active and sham-treated groups, respectively; p=0.0346). The proportion of subjects who achieved wound area reduction (WAR) from baseline at week 12 of ≥90% was significantly higher in the active therapy group. The incidence and nature of infection were consistent with previously published studies, and pain was not increased in the active therapy group. Amputation was insignificantly higher in the sham-treated group and recurrence did not differ. The ESWT device was found to be reliable. Conclusion: The outcomes for the primary and secondary endpoints from these studies show that ESWT administered adjunctively with standard care is an effective advanced therapy for neuropathic DFUs (grade 1A and 2A) that do not respond to two weeks' standard care alone by reducing wound volume by at least 50%.