Is additional hyperbaric oxygen therapy cost-effective for treating ischemic diabetic ulcers? Study protocol for the Dutch DAMOCLES multicenter randomized clinical trial?

The value of hyperbaric oxygen therapy (HBOT) in the treatment of diabetic ulcers is still under debate. Available evidence suggests that HBOT may improve the healing of diabetic ulcers, but it comes from small trials with heterogeneous populations and interventions. The DAMOCLES-trial will assess the (cost-)effectiveness of HBOT for ischemic diabetic ulcers in addition to standard of care. In a multicenter randomized clinical trial, including 30 hospitals and all 10 HBOT centers in the Netherlands, we plan to enroll 275 patients with Types 1 or 2 diabetes, a Wagner 2, 3 or 4 ulcer of the leg present for at least 4 weeks, and concomitant leg ischemia, defined as an ankle systolic blood pressure of <70 mmHg, a toe systolic blood pressure of <50 mmHg or a forefoot transcutaneous oxygen tension (TcpO2) of <40 mmHg. Eligible patients may be candidates for revascularization. Patients will be randomly assigned to standard care with or without 40 HBOT-sessions. Primary outcome measures are freedom from major amputation after 12 months and achievement of, and time to, complete wound healing. Secondary endpoints include freedom from minor amputations, ulcer recurrence, TcpO2 , quality of life, and safety. In addition, we will assess the cost-effectiveness of HBOT for this indication. The DAMOCLES trial will be the largest trial ever performed in the realm of HBOT for chronic ulcers, and it is unique for addressing patients with ischemic diabetic foot ulcers who may also receive vascular reconstructions. This matches the treatment dilemma in current clinical practice