The goal of this clinical trial is to evaluate whether cold atmospheric plasma (CAP) combined with endovascular intervention can accelerate wound healing and improve safety outcomes in patients aged 18 to 80 years with diabetic foot ulcers (DFUs) complicated by lower extremity arterial occlusion.
The main questions it aims to answer are:
1. Does CAP treatment lead to a greater reduction in ulcer area by Week 4 compared to placebo?; 2. Is CAP therapy safe and well-tolerated in patients with DFUs after successful infrapopliteal revascularisation?;
Researchers will compare CAP treatment plus standard care to sham CAP (placebo) plus standard care to see if CAP improves wound healing more effectively and reduces adverse local symptoms.
Participants will:
1. Receive either active CAP therapy or sham CAP therapy once daily for 10 days following endovascular revascularisation 2. Undergo daily wound assessments for ulcer area, signs of infection, and pain scores 3. Complete quality-of-life questionnaires (EQ-5D and SF-12) at baseline and Week 4 4. Be followed through Week 4 to assess efficacy and safety endpoints
1)Age between 18 and 80 years; diagnosed with type 1 or type 2 diabetes mellitus; with HbA1c ≤10%;
2)Presence of at least one chronic foot ulcer persisting for ≥3 weeks, with no signs of healing despite guideline-directed standard care; ulcer classified as Wagner-Armstrong grade 1D or 2D;
3)Imaging-confirmed infrapopliteal arterial stenosis or occlusion, assessed by vascular ultrasound and/or computed tomography angiography (CTA); all patients must have undergone infrapopliteal balloon angioplasty, with successful target vessel revascularisation confirmed intraoperatively (≤30% residual stenosis);
4)Signed written informed consent prior to study participation.
1)Concurrent use of negative pressure wound therapy (NPWT) or maggot debridement therapy;
2)Undergoing dialysis for end-stage renal disease;
3)Use of topical antibiotics with known biological activity on the wound;
4)Use of platelet-rich fibrin (PRF) for wound treatment;
Parallel
Cold Atmospheric Plasma (CAP)
DeviceCAP-activated gas treatment developed by Xi'an Jiaotong University (Chinese patent No. ZL202110209052.X); administered once daily for 10 days, 25 minutes per session.
Sham CAP Therapy
DeviceIdentical equipment without plasma activation; simulates treatment environment (sound, airflow) for participant blinding.
Infrapopliteal Endovascular Revascularisation
Procedure/SurgeryBalloon angioplasty is performed on infrapopliteal arteries with significant stenosis or occlusion. Technical success is defined as \<30% residual stenosis, confirmed intraoperatively by digital subtraction angiography (DSA). Only patients with successful revascularisation are eligible for randomisation.
Guideline-Based Standard DFU Care
Other interventionAll participants will receive diabetic foot ulcer (DFU) care according to current international and Chinese clinical guidelines
Change in ulcer area (cm²)
Ulcer area will be measured at baseline, daily from Day 1 to Day 10, and at Week 4 post-randomisation. Measurements are obtained from calibrated wound photographs and analysed using ImageJ software. Primary endpoint will be analysed using a linear mixed-effects model to evaluate differences between groups over time.
Time to 10% reduction in ulcer area
The time (in days) from baseline to the first documentation of ≥10% reduction in ulcer surface area compared to baseline, as measured by calibrated wound photography analysed using ImageJ software. Ulcer size is measured daily from Day 1 to Day 10 and at Week 4.
Mean change in pain score measured by Visual Analogue Scale (VAS)
Pain severity will be assessed using the 10-point Visual Analogue Scale (VAS), where 0 indicates no pain and 10 indicates the worst pain imaginable. Measurements will be taken at baseline, daily from Day 1 to Day 10, and at Week 4 post-randomisation. Change in VAS score over time will be compared between groups.
Change in quality of life (EQ-5D)
Health-related quality of life will be assessed using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) at baseline and Week 4 post-randomisation. The EQ-5D-5L descriptive system evaluates five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, each scored on a 5-point ordinal scale (1 = no problems, 5 = extreme problems).
Change in quality of life (SF-12)
Quality of life will be assessed using the 12-Item Short Form Health Survey (SF-12) at baseline and Week 4 post-randomisation. The SF-12 is a validated instrument designed to evaluate health-related quality of life across physical and mental health domains. It yields two composite summary scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Each component score typically ranges from 0 to 100, with higher scores indicating better health status.
Incidence of skin irritation
The presence or absence of skin irritation at the treatment site will be recorded by trained clinical staff during each treatment session (Day 1-10) and at Week 4. Skin irritation includes erythema, rash, itching, or other subjective symptoms reported by the participant or observed by the investigator.
Incidence of local bleeding
Bleeding at the wound or treatment site will be assessed by visual inspection and clinical documentation. Events are recorded as present or absent at each time point, and severity (mild, moderate, severe) will be noted if applicable.
Incidence of local burning sensation
Participants will be asked to report any burning sensation at the treatment site during or after CAP exposure. Events will be recorded as present or absent, and graded based on severity. This outcome will help assess the tolerability of CAP treatment.
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Shenyang Medical College
Lead sponsor
Ansteel Group General Hospital
Collaborator
