A new high-quality randomised controlled trial (RCT) reporting a new dressing that helps heal diabetic foot ulcers (DFUs) quicker has been published in the world’s leading diabetes journal, The Lancet Diabetes & Endocrinology. This new RCT reports “LeucoPatch” – a new multi-layered dressing patch made up of the patient’s own blood products – healed DFUs quicker than best practice care alone.
This large RCT was led by global DFU gurus Professors Fran Game & William Jeffcoate (UK), Lise Tarnow (Denmark) and Magnus Londahl (Sweden). If Profs Game & Jeffcoate sound familiar it’s because they were the lead authors of the International Working Group on the Diabetic Foot (IWGDF) wound healing guideline. So, when these guys publish something this big in the world’s leading diabetes journal it must be worth listening to; but as we always say – is this the full story?
What did we know before this study?
While there’s been high-quality RCTs demonstrating interventions that have helped heal DFUs quicker in the past – such as instant total contact casts – this hadn’t been the case for dressings. In fact, the current IWGDF diabetic foot wound healing guideline recommends to “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 studies are small and at high risk of bias.”
But, this situation has recently dramatically changed. This new RCT is now the third high-quality RCT in the past year that has reported on a new wound dressing treatment demonstrated to heal DFU’s quicker, including a: sucrose octasulfate dressing, nitric oxide generating dressing and now LeucoPatch. These new developments led another global diabetic foot guru Prof Mike Edmonds to suggest we are in a renaissance of DFU dressing treatments. But, what is LeucoPatch and what does it do?
LeucoPatch builds on earlier pilot studies showing blood-derived products – such as platelet-rich plasma or fibrin – may promote healing by releasing cytokines and growth factors which in turn promotes angiogenesis and tissue repair. LeucoPatch goes a step further as it’s made from a sample of the patient’s own blood which is placed in a special device in the clinic. It is then spun in a special centrifuge for about 20 minutes to become a multi-layered patch of platelets, fibrin and leucocytes. This resulting LeucoPatch is then cut to size, applied onto the ulcer and a secondary dressing placed over the top. That all sounds somewhat space age doesn’t it? But does it actually work?
What did this new study do then?
This large multi-national, multi-centre and observer-blinded RCT recruited patients with non-infected DFUs from 32 diabetic foot clinics across the UK, Denmark and Sweden. Before they randomized these patients though, they gave them all a four-week “run-in” period of best practice care that followed the IWGDF reporting standards for diabetic foot studies, including regular debridement, appropriate wound dressings and appropriate offloading devices. After this run-in period, the patients that had >50% reduction in the size of their DFU, along with those that had other exclusion criteria such as infection, were further excluded. This left only participants with “hard-to-heal” DFU to be randomised.
This “run-in” period is a critical part of any DFU RCT because we know that DFU’s that reduce in size by >50% after four-weeks of best practice care will most likely heal within 12 weeks anyway. Many DFU RCTs promoting positive healing effects for interventions are often criticized for not including this “run-in” period because their findings are typically from a combination of the new intervention and best practice care, and compared to a control group receiving care of a standard lower than best practice. So, we just can’t tell if the positive healing effects were from the intervention itself or the best practice care.
Yet we digress. After the run-in period all remaining participants had a whole raft of demographics, medical history, DFU and treatment characteristics collected. They were then randomized to continue to receive weekly ongoing best practice care alone (control group) or in combination with the LeucoPatch (intervention group). They were then followed every week for 26 weeks to see who healed and who had adverse events, such as infections or amputations.
At this point we should say that patient’s treatment was at the discretion of their treating clinic and the patients and their clinicians knew which treatment they were getting (not blinded). But, on the flipside all healing outcomes were painstakingly reviewed by independent clinicians (blinded) to independently verify healing. The statisticians analyzing the data were also blinded. Lastly, the study was funded by Reapplix ApS, but the authors declare the company had no other role in the study.
So what did they find?
The study initially recruited 595 patients, but excluded 326 (55%) of those after the four-week run-in period. Interestingly, 215 (36%) of those excluded had healed by >50% in size or became too small to include which highlights the effect that simply using best practice care has on DFU healing. They then randomised the remainder into the two groups (134 control, 132 intervention) and found the groups had nearly identical demographic, medical history, DFU and treatment characteristics.
Next, they found statistically more patients in the LeucoPatch dressing group healed their “hard-to-heal” DFU than the control group after 20 weeks (34% intervention, 22% control). They also found more patients healed in the LeucoPatch group at 12 weeks and 26 weeks, and had faster time-to-healing.
Lastly, they found adverse events were statistically similar in both groups; such as amputations, pain, infections and anaemia. This was an interesting finding as they thought with this dressing made from routinely taking the patients’ own blood that it may cause anaemia, plus with applying the patient’s own leucocytes to their wound it may reduce infection; but neither happened.
What was good or bad about this study?
The main strengths were: i) it was a large multi-centre study randomising only patients that were “hard-to-heal” after receiving best practice care; ii) it reported similar comprehensive baseline characteristics in both groups; iii) it thoroughly followed patients for 26 weeks following best practice care and reporting standards for both groups; iv) healing was diagnosed by expert independent clinicians that did not know which treatment patients got (blinded); and v) it used robust and blinded statistical analyses.
Limitations were: i) patients and clinicians knew which treatment they were getting (not blinded); ii) the control group’s dressing was at the discretion of the treating clinician as they were unable to provide a ‘sham dressing’ for the control group due to ethical concerns; and iii) while the best practice care principle findings were similar for each care principle, the exact treatments were still at the discretion of the treating clinician. But, in saying all that, the strengths to this study by far outweigh the limitations.
So what does that all mean?
Well the authors sum it up nicely, “this trial shows a clinically and statistically significant benefit associated with the weekly application of autologous immune cell, fibrin, and platelet patches (LeucoPatch) in a population of people with hard-to-heal diabetic foot ulcers. The treatment was without apparent (increase in) adverse events, specifically without evidence of new onset anaemia.”
Overall, the high methodological rigor of this RCT along with its demonstrated positive healing effects, suggest LeucoPatch is a very worthwhile dressing to consider for people with “hard-to-heal” DFUs. The authors go on to say the “production of LeucoPatch patches is simple and quick, and the patch is easy to apply during the course of routine clinical practice” and acceptable to patients judging by “the low number of dropouts form the study”. However, we are unsure if LeucoPatch is available in Australia.
But, does this answer the title’s question? Well with three new robust RCTs all showing positive DFU healing findings for three very different wound dressings, we think if we are not already in a new era for wound dressing treatments for DFU then we must be very close. And with the high quality of these RCT’s findings we dare say that the new IWGDF wound healing guidelines – planned for launch in May at the International Symposium on the Diabetic Foot – may just feature several new recommendations for wound dressings to treat DFU that are much more specific than the current general recommendations.
BUT, we should also highlight that the application of these wound dressings alone without best practice care did not produce these positive effects on healing. In fact, the other big finding of this study was the “run-in” period showed that 36% of DFUs were healing quickly when they simply got best practice care. This highlights nicely that people with DFU still need a package of best practice care to heal quickly and on top of that then these new dressings may help accelerate healing even more.
And if you don’t believe us, why don’t you come along and ask the global guru of DFU wound dressings, Prof Fran Game – the lead author of this new RCT and the upcoming new IWGDF diabetic foot wound healing guidelines – at the DFA 2019 conference . Prof Game will be presenting on how we should dress DFUs now and into the future and leading an interactive Wound Workshop.