A large high-quality randomized controlled trial (RCT) on a new dressing for diabetic foot ulcers (DFUs) has just been published in the world’s leading diabetes journal, The Lancet Diabetes & Endocrinology. The RCT was led by the renowned Professor Mike Edmonds from the UK’s Kings College Hospital and included many of the world’s well-known DFU researchers from the UK, Spain, Italy, Germany and France. The study – dubbed the Explorer trial – reports that a sucrose octasulfate impregnated dressing healed neuro-ischaemic DFUs quicker than a control dressing. But, is that the full story?
While there’s been high-quality RCTs demonstrating the effectiveness of interventions to heal DFUs in the past – such as instant total contact casts to heal diabetic foot ulcers – this hasn’t really been the case for wound dressings. In fact, the latest International Diabetic Foot Guidelines simply recommends “select dressings principally on the basis of exudate control, comfort and cost” as “the evidence to support the adoption of any particular (dressing) intervention is poor, because the available studies are small and at high risk of bias.” So what’s different about this Explorer trial then?
Well the Explorer trial was a large rigorous RCT investigating a wound dressing – a multi-national, multi-centre and double-blinded RCT – and reports it is effective to heal DFUs. The authors recruited 240 patients with neuro-ischaemic diabetic foot ulcers from 43 diabetic foot clinics across 5 European countries. They rigorously screened all patients to make sure they were eligible. Patients needed to have a non-infected, neuro-ischaemic DFU of >1cm2 that did not probe to bone, and did not reduce in size by >30% during a 2 week screening phase.
An independent body then randomized all patients to the sucrose octasulfate dressing or control dressing. These dressings were provided with identical packaging and appearance so the patients and treating clinicians could not tell which dressing they received. The only difference was one dressing was impregnated with sucrose octasulfate and the other wasn’t. The authors say they tested 16 independent clinicians and they could not tell which dressing was which.
The authors then used a pre-approved standard treatment study protocol for all patients to try and keep all other DFU treatments the same in both groups. This protocol included regular wound debridement, wound cleansing with sodium chloride, select offloading devices (including total contact casts, instant total contacts, removable cast walkers, customized shoes etc) and dressing changes every 2-4 days. However, treating clinicians did have the ability to change this protocol if they felt it was clinically appropriate, such as choosing the secondary dressings (the sucrose octasulfate dressing still requires a secondary dressing such as a foam), prescribing antibiotics for infection etc.
The researchers collected all demographic, medical history, DFU characteristics and treatments as per those stated in the international standards for reporting DFU studies and our Australian DFU minimum dataset. Patients were then followed monthly until their DFU healed or to a maximum of 20 weeks.
In short, they found that the two groups (126 in the intervention; 114 control) had nearly identical demographics, medical history, DFU characteristics and treatments which meant the randomization worked. Next they found that after 20 weeks, statistically more patients in the sucrose octasulfate dressing group healed their DFU than the control group (48% in the intervention; 30% control). After adjusting for factors that might confound this result – such as country, age, original ulcer size, ulcer duration and amputation history – they still found the intervention dressing had 2.6-fold the odds of healing DFUs at 20 weeks than the control dressing. Additionally they found adverse events were statistically the same in both groups; such as infections, minor amputations, drop outs and deaths.
So what does that all mean? Well the Explorer trial did find quicker foot ulcer healing. The authors conclude it well, “a sucrose octasulfate dressing significantly improved wound closure of neuro-ischaemic diabetic foot ulcers without affecting safety after 20 weeks of treatment along with standard care. These findings support the use of sucrose octasulfate dressing as a local treatment for neuro-ischemia diabetic foot ulcers.”
While this study had many, many strengths – i) international, multi-centre, double-blinded RCT; ii) rigorous eligibility criteria; iii) independent randomization; iv) identical appearance of the intervention and control dressing; v) standardized protocol for all other DFU care; and vi) recommended data collection standards – there were some limitations. These included: i) the study was funded by a wound dressing company which according to the authors did not have any role in the data extraction, analysis or interpretation, but did in the writing of the paper; ii) the definition of ischaemia was a little confusing and seemed to be >50mmHg toe pressure indicating only those with nil or mild ischaemia were included (not moderate and critical ischaemia); iii) different offloading device types were used, and adherence to these devices was self-reported which is not very reliable, but the proportions of devices used and adherence rates were similar in both groups; iv) different broad debridement types were used, but again these were statistically similar in both groups; and v) different secondary dressings were used, but again similar in both groups. In saying all that, the strengths to this study far outweighed the limitations.
Overall, the methodological rigor of this study really sets the standard for future wound dressing studies to achieve. With the quality of this study and its findings we dare say that the new International Guidelines (launched at the International Symposium on the Diabetic Foot in May 2019) will feature a new recommendation, something like ‘to heal a neuro-ischaemic diabetic foot ulcer consider using a sucrose octasulfate impregnated dressing’.
Finally, we hear you ask, what does sucrose octasulfate actually do and where do I get these dressings? In short, chronic wounds (in this case DFUs) have a prolonged inflammatory phase which increases their concentrations of matrix metalloproteinases (MMPs). High MMP concentrations damage growth factors and destroy extracellular matrix, and result in impeded wound healing. However, sucrose octasulfate potassium salt binds with these MMPs to reduce their concentrations and in turn their detrimental effects on wound healing. Sucrose octasulfate dressings have previously been demonstrated to improve healing in other chronic wound types such as venous leg ulcers in the past.
The dressing used is a polyester mesh impregnated with a lipidocolloid matrix containing sucrose octasulfate potassium salt, otherwise known as UrgoStart Contact. At this point we should declare our potential bias as Urgo Medical, the company that funded this RCT and produces these dressings, was the Platinum Sponsor of our recent DFA’s Whats New in DFU Roadshow. However, at DFA we are proud to introduce products to the Australian diabetic foot community that have very high quality evidence to support their claims to heal DFUs; which UrgoStart Contact now does. Products such as these can only bring us closer to our national goal of ending avoidable amputations within a generation.