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

NCT07073040 | Recruiting DMC

• 1 other identifier: PROSPECT
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

Brief Summary

Critical limb ischemia is the end-stage manifestation of peripheral arterial disease (PAD), frequently presenting as ischemic rest pain, ulceration, or gangrene. Diabetes mellitus is a major risk factor for lower extremity arterial occlusion, with infrapopliteal arteries most commonly affected. Patients with diabetic foot ulcers (DFUs) have a high prevalence of neurovascular complications, poor healing, and elevated amputation and mortality rates. Large-scale cohort studies indicate that five-year survival after amputation in this population is only about 50%, underscoring the need for more effective therapies. Endovascular revascularization has become the first-line treatment for diabetic lower limb ischemia. However, despite successful revascularization, persistent microvascular dysfunction and difficult-to-heal ulcers remain common due to chronic inflammation, impaired angiogenesis, and tissue repair deficits. Current advanced wound dressings provide limited benefit and are often costly. Cold atmospheric plasma (CAP) has emerged as a promising adjunctive therapy, with demonstrated antimicrobial activity-including efficacy against multidrug-resistant organisms-and the ability to promote microcirculation and wound healing. CAP generates reactive oxygen and nitrogen species that disrupt bacterial membranes and may also stimulate tissue regeneration. Preclinical and clinical studies suggest that CAP can accelerate healing in chronic wounds and is well tolerated by patients. Given these advantages, the present study aims to assess the efficacy and safety of CAP combined with endovascular intervention in patients with diabetic foot ulcers and lower extremity arterial occlusion, to inform future clinical application of this novel technology.

Conditions

Diabetic Foot Ulcers (DFU); Lower Extremity Arterial Occlusion

Keywords

cold atmospheric plasma; diabetic foot ulcers; lower extremity arterial occlusion

Outcome Measures

Primary Outcomes (1)

• Change in ulcer area between groups

  The ulcer area (cm²) will be measured daily during the first five days, and every other day for the subsequent eight visits (13 follow-up assessments in total)

  From Baseline (Day 0) to Day 21 post-randomization

Secondary Outcomes (9)

• Time to 10% reduction in ulcer area

  From Baseline (Day 0) to Day 21 post-randomization

• Time to 20% reduction in ulcer area

  From Baseline (Day 0) to Day 21 post-randomization

• Time to onset of clinical signs of infection

  From Baseline (Day 0) to Day 21 post-randomization

• Change in pain score

  From Baseline (Day 0) to Day 21 post-randomization

• Change in quality of life (EQ-5D questionnaire)

  Baseline (Day 0) and Day 21 post-randomization

Other Outcomes (6)

• Change in pain score

  Baseline (Day 0), Day 180 ± 15, and Day 360 ± 20 post-randomization

• Change in quality of life (EQ-5D questionnaire)

  Baseline (Day 0), Day 180 ± 15, and Day 360 ± 20 post-randomization

• Change in quality of life (SF-12 questionnaire)

  Baseline (Day 0), Day 180 ± 15, and Day 360 ± 20 post-randomization

Study Arms (2)

CAP therapy

ACTIVE COMPARATOR

Device: Cold atmospheric plasma (CAP); Other: Successful infrapopliteal angioplasty

the placebo group

PLACEBO COMPARATOR

Device: Sham Procedure; Other: Successful infrapopliteal angioplasty

Interventions

Cold atmospheric plasma (CAP) DEVICE

CAP therapy will be administered once daily for the first five days and then every other day thereafter, for a total of 13 sessions. Each session will last approximately 25 minutes, as recommended by the manufacturer. During treatment, the affected limb will be enclosed in a sterile treatment bag, sealed with medical adhesive tape. The CAP device will operate in two sequential modes: a "disinfection mode" delivering ozone-rich (O₃) plasma-activated gas for 20 minutes, followed by a "healing mode" delivering nitric oxide (NO)-rich plasma-activated gas for 5 minutes. All procedures will be performed in accordance with the manufacturer's instructions and the device's standard operating protocol.

CAP therapy

Sham Procedure DEVICE

Participants in the placebo group will undergo a sham procedure, in which the electric field required for plasma generation will be disabled, so that no plasma will be produced. Only the operating sounds of the device will be simulated, ensuring blinding for both participants and clinical staff.

the placebo group

Successful infrapopliteal angioplasty OTHER

All patients will undergo successful infrapopliteal angioplasty, with less than 30% residual stenosis confirmed by digital subtraction angiography.

CAP therapy; the placebo group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18-80 years, with a diagnosis of type 1 or type 2 diabetes and diabetic foot ulcer; glycated hemoglobin (HbA1c) ≤ 10%.
• Presence of at least one chronic foot ulcer persisting for at least three weeks, with no signs of healing after standard-of-care treatment based on current clinical guidelines. The ulcer must be classified as Wagner-Armstrong grade 1D or 2D (Wagner: superficial ulcer \[grade 1\] or ulcer extending to tendon \[grade 2\]; Armstrong: presence of both ischaemia and infection \[stage D\]).
• Documented infrapopliteal arterial stenosis or occlusion by vascular ultrasound and/or CT angiography (CTA), meeting indications for revascularization. All enrolled patients must have received successful infrapopliteal balloon angioplasty, with intraoperative angiography confirming target artery patency.
• Provision of written informed consent.

You may not qualify if:

• Concurrent treatment of the wound with local vacuum therapy or maggot therapy.
• Undergoing dialysis.
• Use of local active antibiotics.
• Treatment with platelet-rich fibrin.
• Women of childbearing potential without effective contraception, or women who are actively breastfeeding.
• Presence of other severe organ dysfunction, with an expected survival of less than six months.
• Participation in another clinical trial within the past three months or currently enrolled in another clinical trial.

Sponsors & Collaborators

• Shenyang Medical College: lead
• Ansteel General Hospital: collaborator
• Tsinghua University: collaborator

Study Sites (1)

Ansteel General Hospital

Anshan, Liaoning, China

RECRUITING

MeSH Terms

Conditions

Diabetic Foot

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies

Study Officials

• Yun-En Liu, MD

  Shenyang Medical College

  STUDY CHAIR

• Lin Tao, MM

  Shenyang Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yun-En Liu, MD

CONTACT

86-24-62215130; lye9901@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants in the placebo group will undergo a sham procedure, in which the electric field required for plasma generation will be disabled, so that no plasma is produced. Only the operating sounds of the device will be simulated, ensuring blinding for both participants and clinical staff.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 29, 2025
• First Posted: July 18, 2025
• Study Start: July 22, 2025
• Primary Completion: April 10, 2026
• Study Completion: May 6, 2026
• Last Updated: January 30, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

CN (1)