Mike Griffiths1

1AOTI (Oceanside, United States)

Advanced Adjunctive Wound Care Treatment Modalities such as Negative Pressure Wound Therapy (NPWT), Full Body Hyperbaric Oxygen Therapy (HBO) and Topical Wound Oxygen Therapy (TWO2), are commonly used to help heal recalcitrant chronic wounds.

This study compares their relative application and the published evidence as to their effectiveness and costs

A thorough literature review was conducted for each modality when utilized in the treatment of Diabetic and Venous ulcers.

Functional and ease of application comparisons between the modalities, as well as their relative clinical and cost effectiveness in healing chronic diabetic and venous ulcers was evaluated

Company Confidential 4

Pubmed search* TOTAL: 317 found articles

Literature retrieved for more detailed Assessment n=82

Literature excluded as not topical oxygen n=235

Literature excluded: Not relevant n=1 Not in English n=3 No human data n=2 Hyperbaric Oxygen n=7 Duplicates n=29

Literature with relevant clinical data n=20

Search in citations of relevant papers and reviews for relevant studies n=13

Including literature cited n=33

*Pubmed search with the following algorithms: topical[All Fields] And "oxygen"[All Fields])And "wound"[All Fields]) n=121 topical[All Fields] And "oxygen"[All Fields])And "ulcer*"[All Fields]) n=69 topical[All Fields] And "oxygen"[All Fields])And "diabetic"[All Fields]) n=41 topical[All Fields] And "oxygen"[All Fields])And "venous"[All Fields]) n=38 topical[All Fields] And "oxygen"[All Fields])And "burn"[All Fields]) n=31 topical[All Fields] And "oxygen"[All Fields])And "graft*"[All Fields]) n=17

Author Published Journal Patients (Treatment/

Control)

Outcome (Complete Healing Rates)

Aburto 2010 (Oral Presentation and published abstract)

International Diabetic Foot Congress

20/20 Diabetic: 90% vs. 40% healed in 12 weeks Venous: 50% vs. 30% healed in 12 weeks

Blackman 2010 OWM 17/11 82% vs. 45% healed (12 wks)

Nie 2010 Journal of Reparative and Reconstructive Surgery

23/18 (Total 85)

Burns: Wound healing rates 85% vs. 68%

Sultan 2010

American Society for Vascular Surgery

46/37 3 year follow up. 80% vs. 14% remained healed at 36 month

Tawfick 2009 European Journal for Vascular Surgery

46/37 80% vs. 35% healed (12 wks)

Heng 2000 OWM 13/27 90% vs. 22% healing (16 weeks)

Leslie, 1988

Author Published Randomized Patients (Treatment/

Control)

Outcome

Doctor 1992 YES 15/15 No data on wound healing 13% vs. 58% amputation (no time given)

Faglia 1996 YES 35/33 No data on wound healing 8.6% vs. 33% amputation (7 weeks)

Kessler 2003 YES 15/13 14% vs. 0% healing after 3 weeks

Abidia 2003 YES 9/8 • 62.5% vs. 12.5% healing at 6 wks • 62.5% vs. 25% at 6 month

Duszun 2008 YES 50/50 No data on healing; 3 year follow up 8% vs. 48% amputation

Löndahl 2010 YES 48/42 • No Difference after 12 wks (12% vs. 2% healing)

• No difference after 6 month, • After 12 month 52% vs. 29% healing

TWO2Heng, 2000

16 wksn=40

TWO2Blackman, 2010

12 wksn=27

TWO2Aburto, 2010

12 wksn=20

HBOAbidia, 2003

1 yearn=17

HBOLöhndahl, 2010

1 yearn=90

Healed inOxygen group

90 82 90 62.5 52

Healed Controls 22 45 10 25 29

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Healing rates in Diabetic ulcers

TWO2Tawfick; 2009

12 wksn=83

TWO2Aburto, 2010

12 wksn=20

HBOHammarlund, 1998

18 wksn=16

Healed inOxygen group

80 50 25

Healed Controls 35 30 0

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Healing rates in Venous ulcers

Author Published Randomized Patients (Treatment/

Control)

Outcome

McCallon 2000 NO 5/5 Mean time to satisfactory healing 22.8 vs. 42.8 days

Armstrong 2005 YES 77/85 Healing in post-amputation wounds 56% vs. 39% in 16 weeks

Blume 2008 YES 169/166 43.2% vs. 28.9% healing in 16 weeks

Vuerstaek 2006 YES 30/30 Venous only: 13/13

• All patients received skin grafting • After 43 days 90% vs. 48% healed • 40% adverse events to compared

to 23% in control group • Reoccurrence rate 52% in VAC vs.

42% in controls after one year

*The study from Eginton, 2003 was not considered as only 6 patients completed the trial

TWO2Heng, 2000

16 wksn=40

TWO2Blackman, 2010

12 wksn=27

TWO2Aburto, 2010

12 wksn=20

NPTArmstrong, 2005

16 wksn=162

NPTBlume, 2008

16 wksn=335

Healed inOxygen group

90 82 90 56 43.2

Healed Controls 22 45 10 39 28.9

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Healing rates in Diabetic foot ulcers

HBO TWO2 NPWT

Institutional Use only Virtually everywhere Virtually everywhere

(FDA warning in non acute sites)

Requires specialized facilities

and personal Only basic training needed

Well trained personal

needed

Systemically oxygenates

blood at 2,500 mb

Topical oxygenation of

wound tissue at 50 mb

Applies a Vacuum

at 75-125 mmHg

Relies on vascular system to

deliver O2

Delivers O2 directly to

superficial tissue even when

severed from circulation

Does not directly

address O2 supply to

wound

Risk of multi-organ toxicity

multiple contraindications

No risks reported

Tremendous pain decrease

in venous patients

A number of deaths

reported due to bleeding

in homecare settings

HBO TWO2 NPWT

Daily travel to facility for

90 min treatment

60 - 90 min treatment

at home

Continuous treatment

at home 24/7

Advanced dressings used in

normal manner

Oxygen permeable

dressings recommended

Commonly applied with

dedicated dressing

Relatively well studied Relatively well studied Well studied

Mechanism of action logical

but with systemic risks

Mechanism of action logical

and most “biological”

Mechanisms of action

logical with some risks

Heals wounds completely Heals wounds completely Supports building of

granulation tissue

Expensive Relatively Inexpensive Relatively Inexpensive

As has been pointed out in many published reviews, the quantity and quality of Randomized Controlled Studies for each of the modalities is limited. This being said, the entire body of published evidence for all three modalities is significant, allowing for meaningful comparisons. With the ever increasing global incidence and resultant costs associated with treating chronic diabetic and venous ulcers, it is critical that both the clinical effectiveness and cost effectiveness of different modalities be considered when making treatment decisions.

Both HBO and TWO2 appear more effective than NPWT in healing chronic Diabetic ulcers. TWOT appears more effective than both HBO and NPWT in healing chronic Venous ulcers. NPWT and TWO2 offer the additional benefit of being deliverable in non-institutional settings where healthcare delivery costs are lower and thereby would likely be more cost effective.