Efficacy and Safety of Cold Atmospheric Plasma Combined With Endovascular Intervention for Diabetic Foot Ulcers With Lower Extremity Arterial Occlusion

Official title

Efficacy and Safety of Cold Atmospheric Plasma Combined With Endovascular Intervention for Diabetic Foot Ulcers With Lower Extremity Arterial Occlusion: A Randomized, Double-Blind, Placebo-Controlled Trial

Overview

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

Detailed description

Diabetic foot ulcers (DFUs) complicated by lower extremity arterial occlusion are difficult to heal, even after successful endovascular revascularisation, due to persistent microcirculatory impairment and chronic inflammation. Cold atmospheric plasma (CAP) has shown promising effects in promoting wound healing through antimicrobial activity, angiogenesis induction, and modulation of inflammatory responses. However, its efficacy and safety in the clinical treatment of DFUs remain to be validated in randomized controlled trials.

This prospective, randomized, placebo-controlled, single-center clinical trial aims to assess the efficacy and safety of CAP therapy, delivered as CAP-activated gas, in patients with DFUs who have undergone successful infrapopliteal balloon angioplasty. Participants will receive either active or sham CAP therapy once daily for 10 days, in addition to standard DFU care. The primary endpoint is the percentage reduction in ulcer area at Week 4. Secondary outcomes include time to early healing response, pain scores, quality of life, and local adverse events.

The results of this study are expected to provide clinical evidence supporting the use of CAP as an adjunctive therapy in ischemic diabetic foot wound management.

Interventions

• Device Cold Atmospheric Plasma (CAP)
  CAP-activated gas treatment developed by Xi'an Jiaotong University (Chinese patent No. ZL202110209052.X); administered once daily for 10 days, 25 minutes per session.
• Device Sham CAP Therapy
  Identical equipment without plasma activation; simulates treatment environment (sound, airflow) for participant blinding.
• Procedure Infrapopliteal Endovascular Revascularisation
  Balloon 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.
• Other Guideline-Based Standard DFU Care
  All participants will receive diabetic foot ulcer (DFU) care according to current international and Chinese clinical guidelines

Primary outcome measures

• Change in ulcer area (cm²) [Time frame: assessed at baseline, Day 1 to Day 10 post-randomisation, and at Week 4]

Secondary outcome measures (4)

• Time to 10% reduction in ulcer area [Time frame: From baseline through Day 10 and Week 4 post-randomisation]
• Mean change in pain score measured by Visual Analogue Scale (VAS) [Time frame: Baseline; daily from Day 1 to Day 10; and at Week 4 post-randomisation]
• Change in quality of life (EQ-5D) [Time frame: Baseline and Week 4 post-randomisation]
• Change in quality of life (SF-12) [Time frame: Baseline and Week 4 post-randomisation]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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;
• 5)Women of childbearing potential without effective contraception, or currently breastfeeding;
• 6)Presence of severe comorbidities involving other organ systems, with an estimated life expectancy of less than 6 months;
• 7)Participation in another clinical trial within the past 3 months, or currently enrolled in another clinical study;
• 8)Any condition deemed unsuitable for trial participation at the discretion of the investigators.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

China · 1 center

• Ansteel Group General Hospital — Anshan

Identifiers

NCT: NCT07198061 · CAP_Foot_Ulcers

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗