A model for diabetic foot ulcer clinical trials on advanced therapies

Randomised controlled clinical trials remain the gold standard in assessing the efficacy of a medical drug, device or intervention. Standardisation in clinical trial design reduces bias, ensures the validity of the trial data, and allows for generalisation of trial results to the larger real-world population which has the disease. Critics of diabetic foot ulcer (DFU) trials point to the inconsistency in endpoints between studies, a lack of translation to the DFU population at large, failure to include the target population in advanced therapies, and a poorly defined standard of care (SoC). These issues of design and conduct were addressed by the Natrox Topical Oxygen Wound Treatment (NOWT) trial. In the past, DFU clinical trials prescribed dressings that were not SoC, such as wet-to-dry gauze, loosely controlled offloading and debridement. The trials failed to concentrate on DFUs that qualified for advanced wound care from a clinical and payer perspective. A four-week run in period to the NOWT trial matched the requirement for 30 days of SoC before instituting advanced therapy. Sharp excisional debridement was mandated and confirmed through digital photography. Total contact casting was used to offload plantar DFUs. This manuscript uses the NOWT trial as a guide for future DFU clinical trial design. Declaration of interest: TS is a consultant for Inotec AMD Ltd., UK. The authors have no other conflicts of interest to declare.