Clinical Evidence

Controlled Studies & Case Studies

AOTI is committed to providing the strongest scientific evidence as to the Efficacy, Clinical and Quality Of Life benefits of our unique Topical Wound Oxygen (TWO₂) therapy. The following table summarizes the already extensive published clinical evidence as to the utility of TWO₂. Additionally, the company is in the process of conducting further clinical trials for different wound types, including a multi-centered, multi-national, placebo controlled, Randomized Controlled Trial of 220 patients, to further investigate the clinical outcomes and cost saving benefits of our therapy in non-healing Diabetic ulcer patients.

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Author	Journal	Study Type	No. of Patients	Ulcer Type	Outcome
Robert G. Frykberg, Peter J. Franks, Michael Edmonds, Jonathan N. Brantley, Luc Téot, Thomas Wild, Matthew G. Garoufalis, Aliza M. Lee, Janette A. Thompson, Gérard Reach, Cyaandi R. Dove, Karim Lachgar, Dirk Grotemeyer, Sophie C. Renton, on behalf of the TWO2 Study Group	Diabetes Care 2019 Oct; dc190476. https://doi.org/10.2337/dc19-0476	A Multinational, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Efficacy of Cyclical Topical Wound Oxygen Therapy (TWO2) in the Treatment of Chronic Diabetic Foot Ulcers: The TWO2 Study	73	Diabetic	TWO2 was shown to be *6 times more likely to heal a DFU at 12 weeks compared to optimal SOC* after adjusting for ulcer severity. TWO2 demonstrated more durable healing with a *6 times lower recurrence rate compared to optimal SOC* with *only 6.7% of Active TWO2 vs 40% of Sham TWO2 ulcers recurring at 12 months.* Primary Endpoint of Ulcers 100% Healed at 12 Weeks: Active TWO2 = 41.7% vs Sham TWO2 = 13.5% (Pearson Chi2 = 7.27, P = 0.007). Likely Healing Outcome at 12 Weeks: Odds ratio (OR) of 4.57 (97.8% CI 1.19, 17.57), P=0.010 After adjustment for University of Texas Classification (UTC) ulcer grade Odds ratio (OR) increased to 6.00 (97.8% CI 1.44, 24.93), P=0.004. The wound care–focused QOL index improved for patients whose ulcers healed with Active TWO2 in all functional domains, with the greatest improvement seen in the Well-Being component that improved 90-fold. For the patients with larger open ulcers at the end of the 12-week active phase, the mean reduction in ulcer area from baseline was *4.12 cm* for Active TWO2 compared with a *1.34 cm* increase for the Sham TWO2.
Frykberg, R et al	American Diabetes Association’s 78th Scientific SessionsLate Breaking Abstract Diabetes, June 2018 Volume 67, Supp 1	Multi-National, Multi-Center, Prospective, Randomized, Double Blinded, Placebo-Controlled Trial	73	Diabetic	41.7% of TWO2 treated ulcers were completely healed compared to just 13.5% of ulcers treated with gold standard-of-care alone at 12 weeks. TWO2 showed nearly 4 times the likelihood to completely heal ulcers compared to gold standard-of-care alone.
Tawfick, W et al	Vascular and Endovascular Surgery	Controlled Cohort Study	132	Venous	Mean reduction in ulcer surface area at 12 weeks was 96% with 76% of ulcers completely healed Median time to full healing was 57 days 6% ulcer reoccurrence after 36 months follow-up
Blackman E et al	Ostomy Wound Management	Prospective Controlled Study	28	Diabetic	82.4% of ulcers completely healed at 12 weeks Median time to full healing was 56 days No ulcer reoccurrence after 24 months follow-up
Ichioka S et al	Wounds International	Case Series	6	Pressure & Diabetic	Improved ulcer healing Increased the oxygen values of peri-wound area
Aburto et al	Journal of Wound Technology	Randomized Controlled Trial	40	Diabetic & Venous	Diabetic ulcers 90% healing in 12 weeks Venous ulcers 50% healed in 12 weeks
Sultan S et al	European Journal of Vascular and Endovascular Surgery	Parallel study	83	Venous	80% ulcers healed at 12 weeks Median time to full healing was 45 days No ulcer reoccurrence after 12 months follow-up Pain score improved from 8 to 3 by day 13
Japour C et al	Desert Foot Conference Proceedings	Case Series	5	Diabetic	Average time to 100% closure was 3.4 months Average number of treatments to closure was 45
Derk F et al	Desert Foot Conference Proceedings	Case Series	9	Diabetic & Dehiscence	Average time to 100% closure was 12.7 weeks
Levine B et al	Desert Foot Conference Proceedings	Case Series	14	Diabetic & Venous	Average time to 100% closure was 11.5 weeks Average number of treatments to closure was 33
Kallianen LK et al	Pathophysiology	Case series	32	Mixed	75% closure rate. No side effects
Edsberg LE et al	Ostomy and Wound Management	Randomized Controlled Trial	8	Pressure	Healing of all wounds
Landau Z et al	Yale Journal Biology & Medicine	Prospective open study	100	Diabetic	81% Healing
Heng MC et al	Ostomy and Wound Management	Prospective Randomized study	40	Pressure	90% closure rate
Heng MC et al	Ostomy and Wound Management	Prospective Study	15	Pressure	Overall improvement in ulcer size over time
Landau Z et al	Arch Orthopedic Trauma Surgery	Prospective study	50	Diabetic	86% closure rate
Heng MC et al	American Journal Dermatopatho.	Case series	6	Pressure	Some clinical improvement
Ignacio DR et al	Journal American Podiatry Asso.	Case series	15	Mixed	73% healing rate
Heng MC et al	Archives Dermatology	Prospective non- randomized study	6	Necrotic Pressure	100% healing in TOT group
Diamond E et al	Journal American Podiatry Assoc	Case series	11	Mixed	100% healing
Olejniezak S	Medical Times	Meta-Analysis Self Control	174	Mixed	Very Effective/ Favorable Results
Fischer BH	Journal Dermatological Surgery	Case series	30	Mixed	Overall positive results
Fischer BH	Lancet	Case series	52	Mixed	Positive results