Trial to Evaluate Cyclical Topical Wound Oxygen Therapy in the Treatment of Chronic Venous Leg Ulcers

NCT06754735 | Recruiting Phase 4 DMC FDA Device

• 1 other identifier: AOTI
• Study Type: interventional
• Target: 212
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the efficacy, safety and economic benefits of Cyclical Pressure Topical Wound Oxygen (TWO2) Therapy in the treatment of venous leg ulcers. Participants will utilize standard of care (SOC) multilayer compression dressings with an inactive wound contact layer. Following a 2-week run-in period with SOC and after meeting all eligibility criteria, subjects will be randomized in a 1:1 ratio with TWO2 therapy or sham control therapy plus SOC. Participants will enter the intervention period of up to 16-weeks, followed by a long-term follow-up period of 52 weeks post randomization.

Conditions

Venous Leg Ulcer (VLU)

Keywords

Ulcer, Wound, Randomized, Oxygen, Placebo, Sham, Venous, Compression; Varicose Veins, Venous stasis ulcer; Topical Oxygen

Outcome Measures

Primary Outcomes (1)

• Incidence of complete wound closure within 16 weeks with the use of Topical Wound Oxygen Therapy (TWO2)

  Percentage incidence of complete wound closure defined as 100% skin re-epithelialization without the need for wound dressing that is confirmed by 2 consecutive study visits 2 weeks apart.

  From Baseline to16 weeks

Secondary Outcomes (16)

• Percentage Area Reduction (PAR)

  Baseline, Week 2, 4, 6, 8, 10, 12, 14 up to 16 weeks (± 2 days)

• Incidence of complete wound closure at 12 weeks

  From Baseline to12 weeks

• Incidence of complete wound closure at 52 weeks

  From week 16 to 52 weeks

• Time to complete wound closure

  Baseline, Week 2, 4, 6, 8, 10, 12, 14 up to 16 weeks (± 2 days), 20, 26, 52 weeks (± 2 weeks)

• Pain Visual Analog Scale (VAS) score

  Baseline weekly up to 16 weeks (±2 days)

Study Arms (2)

Topical Wound Oxygen Therapy Device

ACTIVE COMPARATOR

Topical Wound Oxygen (TWO2) device in combination with the extremity chamber delivers oxygen and cyclical compression to the wound site. The sealed environment created by the extremity chamber is filled with oxygen for a minimum of 120 minutes, 5 times a week over multilayered compression dressings and a wound contact layer.

Device: Topical Wound Oxygen Therapy

Sham Control Topical Wound Oxygen (TWO2) device

SHAM COMPARATOR

A Sham Control Topical Wound Oxygen (TWO2) device in combination with the extremity chamber that does not deliver oxygen and cyclical compression to the wound site. The sealed environment created by the extremity chamber is filled with room air for a minimum of 120 minutes, 5 times a week over multilayered compression dressings and a wound contact layer.

Device: Sham Control Topical Wound Oxygen

Interventions

Topical Wound Oxygen Therapy DEVICE

The active intervention is the application of the Topical Wound Oxygen device that supplies cyclical oxygen pressure directly to the wound site within a sealed environment.

Topical Wound Oxygen Therapy Device

Sham Control Topical Wound Oxygen DEVICE

The sham control intervention is the application of Topical Wound Oxygen device that supplies topical room air to the wound site within a sealed environment.

Sham Control Topical Wound Oxygen (TWO2) device

Eligibility Criteria

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

You may qualify if:

• Adults ≥ 18 years and able to provide written informed consent
• Patients who have a chronic venous leg ulcer (VLU) below the knee at or above the malleolus determined to be due to underlying venous disease
• Venous reflux ≥ 500 mil sec/superficial or 1 sec/deep or venous mapping after interventions following a vascular procedure
• VLU of ≥ 1.5cm2 and ≤ 50cm2 after debridement at study enrolment i.e. Screening visit
• \*Cluster wounds where the sum of the full thickness ulcer area must be ≤ 50cm2
• Study ulcer (current episode of ulceration in case of ulcer recurrence) has been present for at least 6 weeks but no more than 5 years prior to study entry
• The index ulcer has been treated with CCD of at least 30mmHg for ≥ 6 weeks prior to screening.
• Adequate perfusion with Ankle-Brachial Pressure Index (ABPI) of 0.75-1.24 inclusive measured at study entry or within 8 weeks prior to study entry AND TcpO2 \> 30mmHg OR Biphasic arterial duplex below the knee OR Toe pressure \> 30mmHg OR TBI .6
• Wound size reduction in a 2-week run-in period of ≤ 30%
• Subject understands and is willing to participate in the clinical study and comply with weekly visits and follow up regime
• Subject has read and signed IRB/EC approved ICF before screening procedures commence

You may not qualify if:

• Known allergy to any of the protocol-stipulated treatments, or non-tolerance of multilayer, multicomponent compression therapy
• Acute thrombophlebitis or Deep Vein Thrombosis (DVT) and within three months preceding study entry
• Subject awaiting venous ablation or is less than 30 days post ablation
• Surgery during three months prior to study entry (such as abdominal, gynecological, hip or knee replacement)
• Wound etiology of uncertain origin or history or prior diagnosis of Systemic Lupus Erythematosus, Burger's Disease, Pyoderma Gangrenosum or other inflammatory ulceration, vasculitis
• Documented evidence of osteomyelitis on any part of affected limb
• Index ulcer has exposed bone, muscle and tendon
• Index ulcer exhibits signs of unmanaged wound infection or severe clinical infection that requires hospitalization or immediate surgical intervention
• BMI \> 45
• Uncontrolled diabetes: HbA1c \> 12% within 60 days of screening
• Renal dialysis or of screening EGFR less than 30 mg/dl
• NYHA Class IV
• Peripheral arterial reconstruction/revascularization on the affected limb within the last 30 days
• Any medication deemed by the Investigator to potentially interfere with the study treatment (e.g. systemic steroids \> 10mg daily dose, immunosuppressive agents).
• Active systemic treatment for malignancy

Sponsors & Collaborators

• AOTI Ltd.: lead

Study Sites (1)

Vascular Institute of New York

New York, New York, 10016, United States

RECRUITING

Related Publications (3)

• Frykberg RG, Franks PJ, Edmonds M, Brantley JN, Teot L, Wild T, Garoufalis MG, Lee AM, Thompson JA, Reach G, Dove CR, Lachgar K, Grotemeyer D, Renton SC; TWO2 Study Group. A Multinational, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Efficacy of Cyclical Topical Wound Oxygen (TWO2) Therapy in the Treatment of Chronic Diabetic Foot Ulcers: The TWO2 Study. Diabetes Care. 2020 Mar;43(3):616-624. doi: 10.2337/dc19-0476. Epub 2019 Oct 16.

  PMID: 31619393 BACKGROUND

• Tawfick WA, Sultan S. Technical and clinical outcome of topical wound oxygen in comparison to conventional compression dressings in the management of refractory nonhealing venous ulcers. Vasc Endovascular Surg. 2013 Jan;47(1):30-7. doi: 10.1177/1538574412467684. Epub 2012 Dec 5.

  PMID: 23223182 BACKGROUND

• Fowkes FG, Evans CJ, Lee AJ. Prevalence and risk factors of chronic venous insufficiency. Angiology. 2001 Aug;52 Suppl 1:S5-15. doi: 10.1177/0003319701052001S02.

  PMID: 11510598 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Varicose Ulcer; Ulcer; Wounds and Injuries; Varicose Veins

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Mike Griffiths, DProf, DMS, CRT, FCMI

  AOTI Ltd.

  STUDY CHAIR

• Anil Hingorani, MD

  PRINCIPAL INVESTIGATOR

• Wael Tawfick, MB.BCH, MRCSI.

  University of Galway

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Despina Herodotou, MRCPod, DABPMi

CONTACT

1-760-431-4700; despi.herodotou@aotinc.net

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The Trial Monitor will be blinded to the participant's allocated intervention.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, Double Blinded, Placebo-controlled Trial

Study Record Dates

• First Submitted: December 16, 2024
• First Posted: January 1, 2025
• Study Start: January 15, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: November 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)