**Background**

After examining the evidence, the Centers for Medicare & Medicaid Services
(CMS) responded to a reconsideration request to remove the coverage exclusion
of continuous diffusion of oxygen therapy (CDO) from the National Coverage
Determination (NCD) Manual and decided that no NCD was appropriate concerning
the use of topical oxygen for the treatment of chronic wounds. CMS amended NCD
20.29 by removing Section C. In their decision, CMS allowed coverage of
topical application of oxygen for the treatment of chronic wounds to be
determined by the local contractors and Medicare coverage of topical oxygen.

**Definitions and Scope**

This is a non-coverage local coverage determination (LCD) for topical oxygen
therapy (TOT). TOT administered to the open wound in small limb-encasing
devices is not typically hyperbaric oxygen (HBO) therapy, and its efficacy has
not been established due to the lack of controlled clinical trials. In
addition, in vitro evidence suggests that TOT does not increase tissue oxygen
tension beyond the superficial dermis. Examples of TOT devices are TOPOX
portable HBO extremity and sacral chambers (Jersey City, NJ), Oxyboot and
Oxyhealer from GWR Medical, L.L.P. (Chadds Ford, PA).

This A/B MAC considers TOT to be a method whereby a local supply of oxygen is
applied to a wound (Dissemond, Kroger, Storck, Risse, & Engels, 2015). It is
delivered by 1 of 2 techniques (Woo, Coutts, & Sibbbald, 2012). In the first,
oxygen may be delivered intermittently through an airtight chamber or soft
sided 'bag' that is sealed around a wound present on the trunk or limb of the
body. The bag or chamber is filled with 100% oxygen at high flow rates (e.g.,
10L /min) from an external source to pressures slightly above atmospheric
(e.g., 1.004 - 1.013 atm abs) and is delivered to the patient on an
intermittent dosing schedule (Feldmeier et al., 2005; Howard et al., 2013). In
the past, this type of oxygen delivery was known by some as topical HBO
therapy, a term that is less commonly used today due to the low pressures
delivered (Brimson & Nigam, 2013). Topical oxygen can also be delivered to a
wound when applied continuously by a tube supplying pure oxygen at a
normobaric pressure and low flow rate (3-12 ml/hour) under an occlusive
dressing (Howard et al., 2013). These devices have been variously termed
transcutaneous oxygen, transdermal continuous oxygen therapy (TCOT), low flow
oxygen, topical continuous oxygen therapy, continuous topical oxygen and CDO
(Dissemond, Kroger, Storck, Risse, & Engels, 2015; Howard et al., 2013;
Lowell, Nicklas, Weily, Johnson, & Lyons, 2009; Orsted et al., 2012; Woo et
al., 2012).

Neither intermittent nor continuous provision of topical oxygen is dependent
on the systemic circulation reaching the wound, as is the case with HBO.
However, because these systems directly apply oxygen to the wound site, it is
thought by some that the oxygen can penetrate directly into the injured area,
and therefore, improve healing of cutaneous lesions (Brimson & Nigam, 2013;
Howard et al., 2013; Orsted et al., 2012; Woo et al., 2012). Typically,
intermittent TOT treatments would be administered 4 to 5 days a week for
approximately 90 minutes per session (Howard et al., 2013), though there can
be other variations of dosaging noted in the clinical protocols. HBO must be
provided in medically supervised environments; however, intermittent TOT may
be provided in the home setting by a well-trained patient or caregiver. Though
infrequent, side effects of HBO can be significant and include the possibility
of pneumothorax, ear and sinus barotrauma, pulmonary edema, worsening of
congestive heart failure, seizures and retinal damage (Howard et al., 2013).
There are also significant concerns among some in the wound care community
regarding TOT administered intermittently. For example, some believe that
intermittent TOT may impede arterial or capillary circulation, inhibit
angiogenesis, and decrease collagen synthesis and fibroblast proliferation;
all circumstances which would delay or inhibit healing of a wound (Mutluoglu,
Cakkalkurt, Uzun, & Aktas, 2015). TOT may not be appropriate for wounds
covered in eschar or those that are deep and penetrating. Moreover, when used
on open, exposed wound surfaces, TOT may cause desiccation of the area (Howard
et al., 2013). TOT has been proposed in the treatment of skin ulcerations
resulting from diabetes, venous stasis, post-surgical infections, gangrenous
lesions, pressure ulcers/decubitus ulcers, infected residual limbs, skin
grafts, burns and frostbite.

The goal of topical continuous oxygen therapy is to provide an uninterrupted
and continuous supply of oxygen to a moist wound. The dressing is designed
such that the oxygen is supplied in a manner that most closely approximates
the normal diffusion of oxygen in moist tissues, yet a rate sufficient to fuel
the increased oxygen demands required in healing tissues. With this therapy,
the dressing helps provide an environment for optimal wound healing while
managing wound exudate levels, protecting against wound dehydration and
protecting against external contamination. Contraindications to this wound
therapy includes wounds with inadequate perfusion to support healing; ulcers
due to acute thrombophlebitis; ulcers due to Raynaud's disease; necrotic
wounds covered with eschar or slough; wounds with fistulae or deep sinus
tracts with unknown depth.

The following are Federal Drug Administration (FDA)-approved TOT devices:

  * EPIFLO TCOT (Ogenix) consists of a small, silent, disposable, oxygen concentrator and a long sterile cannula (tube). It is used with any fully occlusive sterile wound dressing to continuously blanket the wound with near 100% oxygen. The patient is free to ambulate and can continue with normal daily living activities while being treated 24 hours per day. EPIFLO can be worn near the wound beneath clothing without impairing its operation. EPIFLO extracts oxygen from the air, concentrates it to near 100%, and "pumps" the oxygen through the cannula to blanket the wound. The wound is covered with a fully occlusive dressing of the provider's choice. The dressing does not inflate and the patient has no sensation of air movement. EPIFLO provides a silent, continuous, slow flow of oxygen (3 ml/hr for 15 days) that will not dry out the wound. 
  * TransCu O2 wound care device or EO2 system (EO2 Concepts) is a portable oxygen delivery system that provides a continuous flow of oxygen to a wound. Through a dressing attached to the device, oxygen is provided directly to the wound for 24 hours per day, 7 days a week. Oxygen is an important part in the wound healing process. The EO2 system employs a TransCu O2 device, which uses fuel cell technology to continuously generate pure humidified oxygen at adjustable flow rates from 3-15 ml/hr and delivers it directly to the wound bed environment within the OxySpur dressing. The OxySpur Oxygen Diffusion Dressing is an all-in-one dressing for medium to high exudating wounds. Its design allows distribution of oxygen over the entire wound.
  * O2Boot and O2Sacral (GWR Medical, Inc) are portable and 1-time use devices applied and secured to the body by a hypo-allergenic adhesive seal. The area surrounding the wound receives 100% oxygen at 1.03 atm for 90 min for 4 consecutive days, followed by 3 days without treatment. The weekly treatment regimen is self-administered in the patient's home and continued as directed by the healthcare provider.

The Undersea and Hyperbaric Medical Society issued the following policy
statement on topical oxygen, often referred to as "topical hyperbaric oxygen
therapy" (Feldmeier et al., 2005): "1. Topical oxygen should not be termed HBO
since doing so either intentionally or unintentionally suggests that TOT is
equivalent or even identical to HBO. Published documents reporting experience
with topical oxygen should clearly state that topical oxygen not HBO is being
employed. 2. Mechanisms of action or clinical study results for HBO cannot and
should not be co-opted to support topical oxygen since HBO therapy and topical
oxygen have different routes and probably efficiencies of entry into the wound
and their physiology and biochemistry are necessarily different. 3. The
application of topical oxygen cannot be recommended outside of a clinical
trial at this time based on the volume and quality of scientific supporting
evidence available, nor does the Society recommend third party payor
reimbursement. 4. Before topical oxygen can be recommended as therapy for non-
healing wounds, its application should be subjected to the same intense
scientific scrutiny to which systemic hyperbaric oxygen has been held".

Limb-specific TOT entails sealing an individual's arm or leg into an air-tight
plastic container that is sealed with pliable gaskets and exposing the limb to
pure oxygen greater than 1 atm of pressure. Much of the research on this form
of therapy has centered on chronic wounds arising in individuals with diabetic
foot ulcers (DFUs). However, there is currently insufficient evidence from
routine clinical trials (RCTs) to determine the effectiveness of limb-specific
TOT.

In 2008, Banks et al. examined the effectiveness of the EPIFLO device as an
adjunct treatment modality in chronic wound management. This study included 3
men with spinal cord injury (SCI), who each presented with a stage IV pressure
ulcer in the pelvic region. They were treated with the EPIFLO device as an
adjunct therapy. In Case 1, the patient was monitored for 9 weeks, whereas in
Cases 2 and 3, the patients were monitored for 5 weeks. Healing was determined
on a weekly basis by wound dimensions and volume, which were compared before
and after the intervention. Comparison of pre- and post-treatment outcome
measurements showed significant improvement with EPIFLO in each case. The
authors concluded that EPIFLO seems to have had a positive effect on the
healing rate of chronic pressure ulcers in individuals with SCI. The findings
of this small case-series study need to be validated by well-designed studies.

In 2008, Bakri et al. tested the hypothesis that local transdermal delivery of
oxygen improves oxygenation in sternotomy wounds after cardiac surgery; the
secondary hypothesis was that supplemental inspired oxygen improves sternal
wound PsqO(2). After undergoing cardiopulmonary bypass, a total of 30 patients
randomly received EPIFLO oxygen generators that provided oxygen at 6 ml/hr
into an occlusive wound dressing, or identical-appearing inactive generators.
PsqO(2) and temperature were measured in the wound approximately 5 mm below
the skin surface. PsqO(2) and arterial oxygen (Pao(2)) were measured 1 hr
after intensive care unit admission (Fio(2) = 60%) and on the 1st and 2nd
post-operative mornings at Fio(2) of both 30% and 50% in random order. Data
from 4 patients were excluded for technical reasons. Patient characteristics
were similar in each group, as were type of surgery and peri-operative
management. Increasing Fio(2) from 30% to 50% improved Pao(2) from 99 [84 to
116] to 149 [128 to 174] mm Hg (p < 0.001, mean [95% CI]) and sternal wound
PsqO(2) from 23 [16 to 33] to 27 [19 to 38] mm Hg (p < 0.001). In contrast,
local oxygen delivery did not improve tissue oxygenation: 24 [14 to 41] versus
25 [16 to 41] mm Hg (p = 0.88). The authors concluded that additional inspired
oxygen improved Pao(2) and sternal wound PsqO(2) after cardiopulmonary bypass
surgery, and may, consequently, reduce infection risk. However, oxygen
insufflated locally into an occlusive dressing did not improve wound PsqO(2)
and, therefore, does not appear to be useful clinically in cardiac surgery
patients to reduce sternal wound infections.

In 2017, Purvis et al. performed a retrospective chart review of records
collected between January 1, 2007, and July 18, 2016, from male and female
patients ranging in age from 4 years to 105 years. All wounds were at least 1
cm2 and were treated with at least 1 separate modality before treatment with
GWR Medical's single-use, disposable O2Bootor O2Sacral device, and then
treated with O2Boot or O2Sacral device for a minimum of 2 weeks in
compliance with the FDA-approved indications. The treatment was associated
with an overall rate of 59.4% for a reduction in chronic wound size, while
41.6% of wounds had no healing. The overall amputation rate was 2.4% for
wounds in this study.

In 2009, Gordillo et al. reviewed the evidence including in vitro, preclinical
data and clinical data regarding the use of TOT in the treatment of lower
extremity wounds. RCTs are not yet reported and clearly necessary. The authors
concluded the current body of evidence suggests that TOT may be considered as
a second line of therapy for refractory wounds.

In 2010, Schreml et al. noted that oxygen is a pre-requisite for successful
wound healing due to the increased demand for reparative processes, such as
cell proliferation, bacterial defense, angiogenesis and collagen synthesis.
The author stated that even though the role of oxygen in wound healing is not
yet completely understood, many experimental and clinical observations have
shown wound healing to be impaired under hypoxia. However, this review did not
provide any clinical data to support the use of TCOT for wound healing.

In 2010, Blackman et al. examined the clinical efficacy of a pressurized TOT
(TWO2) device in outpatients (n = 28) with severe DFUs referred for care to a
community wound care clinic and evaluated ulcer reoccurrence rates after 24
months. A total of 17 patients received TWO2 5 times per week (60-min
treatment, pressure cycles between 5 and 50 mb) and 11 selected a silver-
containing dressing changed at least twice per week (control). Patient
demographics did not differ between treatment groups, but wounds in the
treatment group were more severe, perhaps as a result of selection bias. Ulcer
duration was longer in the treatment (mean of 6.1 months, SD 5.8) than in the
control group (mean of 3.2 months, SD 0.4) and mean baseline wound area was
4.1 cm2 (SD 4.3) in the treatment and 1.4 cm2 (SD 0.6) in the control group (p
= 0.02). Fourteen of 17 ulcers (82.4 %) in the treatment group and 5 of 11
ulcers (45.5 %) in the control group healed after a median of 56 and 93 days,
respectively (p = 0.04). No adverse events were observed and there was no re-
occurrence at the ulcer site after 24 months' follow-up in either group. The
authors noted that although the absence of randomization and blinding may have
under- or over-estimated the treatment effect of either group, the significant
differences in treatment outcomes confirmed the potential benefits of TWO2 in
the management of difficult-to-heal DFUs. Moreover, they stated that clinical
efficacy and cost-effectiveness studies, as well as studies to elucidate the
mechanisms of action of TWO2 are needed.

In 2012, Woo et al. evaluated the effectiveness of TCOT on chronic wound
healing in 9 patients. After 4 weeks of treatment, mean wound surface area and
wound infection check-list scores were significantly reduced. Signs of
bacterial damage were also reduced. The authors concluded that findings from
this study suggested TCOT may be beneficial in promoting chronic wound
healing. These preliminary findings from a small pilot study need to be
validated by well-designed studies.

In 2014, Brannick et al. evaluated the diagnostic workup and treatment of a
patient with a history of venous insufficiency and a large, painful non-
healing ulcer and the use of CDO therapy to facilitate healing. This case
study involved a 53-year-old female. The initial lower extremity physical exam
revealed lower extremity hyperpigmentation and hemosiderin deposition in the
bilateral gaiter area. Full thickness ulceration to the level of the dermis
was present in the medial right ankle at the level of the medial malleolus.
The ulcer measured 6.7 cm x 5.3 cm. Hypergranulation tissue was present at the
wound base. The wound was well circumscribed and irregularly shaped with
erythematous borders. Active serous drainage was present. There was no odor,
no purulence and no gross signs of infection. CDO therapy as a treatment
modality was implemented using TransCu O2 EO2 Concepts at 10ml/hr followed
by a 4 layer compression dressing. The patient's ulcer pain ranged from 3/10
to 8/10 on the visual analog scale (VAS) throughout the 5-month duration of
the ulcer, requiring the patient to take pain medications when needed. The
patient reported a pain level of only 2/10 after 20 days of CDO treatment and
did not need additional pain medication at that time. At the 20-day mark, the
CDO therapy was temporarily discontinued, as the patient was leaving town for
a holiday. The patient returned to the clinic 6 days later (day 26 since
beginning continuous therapy) and related 10/10 pain and difficulty sleeping.
CDO treatment was resumed. Three days after restarting the therapy, the
patient demonstrated adequate pain control and discontinued taking narcotic
pain medications. The wound measurements taken at day 54 of treatment were 3.6
cm x 1.3 cm with mild hypergranulation. Complete wound closure occurred in 79
days with 100% epithelialization over the hypergranulation tissue. The authors
concluded the treatment and management of chronic wounds can often be
challenging. Oxygen is necessary for both cellular metabolism and host
defense. CDO is capable of delivering continuous oxygen without pressure and
at a low flow rate to a chronic wound. In addition, this device does not
compromise the normal dressings or patient mobility. This case study concludes
that it demonstrates a successful use of CDO in healing a chronic painful
large wound. However, causality cannot be concluded from this study;
therefore, RCTs are needed to assess the effectiveness of this therapy.

In 2015, Niederauer et al. assessed the use of CDO therapy to sham therapy in
the treatment of DFUs in a prospective randomized double-blind multicenter
study. One hundred subjects were enrolled and randomized with DFUs, 79% male
aged 58.3 +/- 12.1 years were to receive either active CDO therapy using an
active CDO device, or an otherwise fully operational sham device that provided
moist wound therapy (MWT) without delivering oxygen. Patients were followed to
closure or 12 weeks, whichever was sooner. Patients, treating physicians and
independent evaluators were blinded to the study arm. All patients received
identical offloading, dressings and follow-up. There were no significant
differences in assessed descriptive characteristics between the treatment arms
(P > 0.5 for all). A significantly higher proportion of people healed in the
active arm compared to sham (46% vs 22%, P = 0.02). This relative effect
became greater in more chronic wounds (42.5% vs 13.5%, P = 0.006). Patients
randomized to the active device experienced significantly faster rates of
closure relative to the sham (P < 0.001). The authors concluded a
significantly greater percentage and rate of healing in patients receiving CDO
therapy compared to a sham device providing standard wound therapy. The study
revealed that CDO therapy appears to have a similar or greater effect as the
wound size increases. Furthermore, the relative effect of CDO therapy on more
chronic wounds appears to be more pronounced as the wounds become more
chronic. These results appear to indicate that with more chronicity and size,
the greater the apparent effect. We look forward to further works that may
confirm or build on these data.

**Level of evidence**

Quality - **Poor quality**

**Strength of Recommendation**

Strength - **Weak**

This A/B MAC evaluated relevant clinical evidence to determine whether or not
the evidence is of sufficient quality to support a finding that an item or
service falling within a benefit category is reasonable and necessary for the
diagnosis or treatment of illness or injury or to improve the functioning of a
malformed body member under 1862(a)(1)(A) of the Social Security Act. The
critical appraisal of the evidence enables determination as to what degree we
are confident that: 1) the specific assessment questions can be answered
conclusively; and 2) the intervention will improve health outcomes for
beneficiaries. An improved health outcome is 1 of several considerations in
determining whether an item or service is reasonable and necessary.  

Based on review of the peer-reviewed medical literature, the evidence includes
a randomized comparative controlled trial and other studies cited. Although
these study results may be promising in regard to TOT, also known as TCOT or
CDO therapy as a treatment modality for including, but not limited to, chronic
non-healing wounds, further randomized comparative controlled studies are
needed to assess the effectiveness of this therapy. Currently there are no
society guidelines that provide recommendations regarding the use of TOT.
Furthermore, we can find no standard definition describing the technology
adopted by medical societies. Lastly, we have not been able to identify a
population of patients or wound characteristics that respond to TOT.  The
evidence is insufficient in determining the effects of this technology on net
health outcomes. This A/B MAC has rendered the LCD for TOT as non-covered.