Cold atmOspheric plaSMa Therapy Versus standArd Wound Care in Diabetic Foot and Venous Leg ulcerS (COSMAS)

Cold atmOspheric plaSMa Therapy Versus standArd Wound Care in Diabetic Foot and Venous Leg ulcerS - a Randomized Controlled Trial

Chronic wounds such as diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) pose a major health burden to the patients but also to the healthcare system because of their distorted healing capacity. This is mainly due to a prolonged treatment duration, high recurrence rates and substantial healthcare costs in wound care. Current guidelines exist that outline the standard wound care (SWC) in these patient groups but it often fails to achieve timely healing. Cold atmospheric plasma (CAP) is an emerging technology with promising antimicrobial and wound healing properties. In vitro and in vivo studies have highlighted the ability of CAP to reduce the bacterial biofilm load and stimulate tissue regeneration and microcirculation. This Randomized Controlled Trial (RCT) aims to evaluate the clinical effectiveness and cost-effectiveness of CAP in addition to SWC in patients with a DFU and VLU.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetic Foot Ulcer; Venous Leg Ulcer
• Intervention / Treatment: Device: COLD ATMOSPHERIC PLASMA

• Study Type: Interventional
• Enrollment (Estimated): 494
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mikaella Loizou; Phone Number: +31639137130; Email: m.loizou@antoniusziekenhuis.nl
• Study Contact Backup: Name: Olaf Bakker; Phone Number: +31883201953; Email: o.bakker@antoniusziekenhuis.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. is referred to one of the participating hospitals for treatment of a diabetic foot ulcer (DFU) or venous leg ulcer (VLU) with healing stagnation and

  a. For VLU: i. An ulcer on the lower leg resulting from malfunctioning venous valves in the leg veins.

  b. For DFU: i. An ulcer on the foot or lower leg in person with currently or previously diagnosed diabetes mellitus and usually accompanied by neuropathy and/or peripheral artery disease (PAD) in the lower extremity Note: In patients with both diabetes and chronic venous insufficiency, ulcers will be categorized as DFU in case of symptoms of diabetic neuropathy or loss of protective sensation, and otherwise categorized as VLU.

  2. has a wound with a minimum wound surface area of 0.5 cm2 and a maximum diameter of 6 cm (~28 cm2 wound surface area for circular wounds; measured after debridement),

  3. has a minimum age of 18 years old.

Exclusion Criteria:

• 1. the participant has one or more of the following contraindications for PLASOMA:

  1. extreme exudative wounds, i.e. wounds in which moisture is visible within seconds after patting dry;
  2. any implanted active electronic device, such as a pacemaker, is present;
  3. an electronic medical device attached to the body, for example electronic life support equipment, a hearing aid, insulin pump or dialysis machine. If this medical device can be disconnected, PLASOMA treatment may be performed. If the sole purpose of this medical device is monitoring, such as a glucose sensor, PLASOMA treatment is not contra-indicated but note that use of PLASOMA together with such devices has not been tested and may lead to erroneous operation of the attached device during PLASOMA treatment;
  4. metal in the area 10 cm around pad-electrode area, e.g. metal sutures and implants;
  5. connection from outside the body to (near) the heart is present, e.g. a central venous catheter;
  6. the participant has epilepsy;

  7. the participant is pregnant.

     2. the participant has more than one wound that requires professional wound care.

     3. for DFU the WIfI-classification is wound grade 3, defined as an extensive, deep ulcer involving forefoot and/or midfoot; deep, full thickness heel ulcer + calcaneal involvement.

     4. presence of ischemia grade 2 or 3, according to the WIfI classification (= the ankle-brachial pressure index (ABI) is ≤0.59 OR the ankle systolic pressure is ≤69 mmHg OR the toe pressure is ≤39 mmHg; there should be at least one of these three measurements available).

     5. a deep infection defined as an infection of the wound involving structures deeper than skin and subcutaneous tissues (e.g., abscess, osteomyelitis, septic arthritis, fasciitis).

     6. the wound is located on a toe.

     7. the participant receives treatment with immunosuppressive agents or oral corticosteroids; no exclusion if participant has received a stable dose for at least 2 months and the oral corticosteroid dose does not exceed 7.5 mg/day prednisone or equivalent.

     8. the participant is receiving or likely to receive offloading with a total contact cast or advanced wound therapies - such as negative pressure therapy, hyperbaric oxygen therapy, biologicals (e.g. skin substitutes, growth factors), electrophysical therapy - for the to be-treated wound. Advanced wound dressings (including but not limited to hydrocolloid, hydrogel, alginate, collagen and antimicrobial dressings) are not excluded.

     9. presence of a chronic or active skin disorder that may negatively influence wound healing (such as Marfan or Ehlers-Danlos syndrome).

     10. the participant takes part in another study that is likely to compromise the outcome of this study or the feasibility of the participant fulfilling this study.

     11. the participant is lactating.

     12. the participant is unable to provide consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cold atmospheric Plasma; Cold Atmospheric Plasma Treatment 2x per week	Device: COLD ATMOSPHERIC PLASMA; Cold Atmospheric plasma treatment in addition to standard wound care
No Intervention: Standard Wound Care; The use of standardized wound care 2x per week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ulcer-free survival days	number of days within the follow-up period (until 26 weeks after the start of the treatment) where the participant is alive and has no ulcer on the same anatomical location of the same foot or limb	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life (QoL)	The quality of life will be determined using the questionnaires EQ-5D-5L (generic). EQ-5D-5L descriptive system is divided into five levels of perceived problems: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. LEVEL 1: no problem LEVEL 2: slight problems LEVEL 3: moderate problems LEVEL 4: severe problems LEVEL 5: unable to/extreme problems Best outcome is therefore a score of 1 in all categories (total score=5), and worst outcome is a score of 5 in all categories (total score=25).	baseline, 13 weeks and 26 weeks
Wound Quality of Life (Wound-QoL)	The wound-QoL (wound-specific Quality of Life) will also be measured since complex wounds have a major impact on patients' well-being. The questionnaire is made of three subscales, body, psyche and everyday life. Answers to each item are coded with numbers (0='not at all' to 4='very much'). Minimal score is therefore 0 (no impairement) and maximal 17 (maximum impairement). The higher the outcome the worst the quality of life.	baseline, 13 weeks, 26 weeks
Wound healing rate	is defined as the percentage of wounds that are healed	26 weeks
time to wound healing	defined as the period measured in days between the start of the treatment period and confirmed wound healing as defined under primary endpoint	26 weeks
Surface area reduction	defined as the percentage of wound area reduction, measured using the eKare insight app, which automatically measures the wound metrics. Surface area reduction can show the added value for wounds that are not healed	26 weeks
Recurrences	presence of an ulcer at the same anatomical location of the same foot or limb of the initially treated ulcer	26 weeks
Development of new ulcers	defined as a new break in the skin not classified as a recurrence, thus not on the same location as the initially treated ulcer	26 weeks
Wound pain	Chronic wound pain level is evaluated using question 1 of the Wound-QoL (quality of life) questionnaire to identify any reduction in wound pain. Answers are coded with numbers (0='not at all' to 4='very much'). Minimal score is therefore 0 (no impairement) and maximal 4 (maximum impairement). The higher the outcome the worst the pain level.	26 weeks
Wound infection	the percentage wound infections is another measure of treatment efficacy, as CAP is bactericidal, and may indicate potential for reduction in use of antibiotics	26 weeks
Occurence of adverse events	will be recorded according to article 80 of the Medical Device Regulation	26 weeks
presence of amputations	presence of amputations on the same limb as the treated ulcer, occurring during the treatment or follow-up period (classified as yes/no).	26 weeks
Cost of Care	the total healthcare costs related to the treatment of the ulcer during the treatment and follow-up period, including the costs of wound care materials, healthcare professional time, hospital visits, interventions and other medical resource use	26 weeks
Cost Effectiveness	the cost per unit of clinical benefit evaluated by comparing the total costs between the intervention and control group in relation to the primary outcome	26 weeks

Collaborators and Investigators

• Sponsor: Olaf Bakker

Study record dates

Study Major Dates

• Study Start (Estimated): November 30, 2025
• Primary Completion (Estimated): May 30, 2028
• Study Completion (Estimated): November 30, 2028

Study Registration Dates

• First Submitted: November 17, 2025
• First Submitted That Met QC Criteria: November 24, 2025
• First Posted (Actual): November 26, 2025

Study Record Updates

• Last Update Posted (Actual): November 26, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Diabetes Mellitus; Diabetic Angiopathies; Diabetes Complications; Skin Diseases; Skin Ulcer; Varicose Veins; Leg Ulcer; Diabetic Neuropathies; Foot Ulcer; Skin and Connective Tissue Diseases; Varicose Ulcer; Diabetic Foot
• Other Study ID Numbers: NL009805 (Other Identifier: COSMAS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No