Hyperbaric OXygen therapy for ACute Acoustic Trauma

Acute acoustic trauma (AAT) is a form of acute sensorineural hearing loss
caused by blast injury or high impact noise. AAT is relatively common in the
military, AAT has continued to a mass veteran disability at a 13-18% annual
rate in the USA. Of the 2.35 million unique cases of auditory system disability
at the end of 2013, approximately 870,000 are attributed to the Gulf War era
and approximately 551,000 from exposure during operations in Iraq and
Afghanistan.5 In the United States military, the estimated costs for
compensation and care of hearing loss and auditory system approaches $1.2
billion for over 1.8 million Veterans.6 These numbers are not published for the
Dutch military.

In the Netherlands, the treatment protocol in the military is the combination
therapy of hyperbaric oxygen therapy (HBOT) and oral corticosteroids. The
rationale for this therapy is that corticosteroids may reduce the inflammatory
response while HBOT reduces the amount of hypoxia caused by the acoustic
trauma. Several preclinical studies have shown beneficial effects of HBOT in
AAT models. Lamm et al. assessed the effects of HBOT in an experimental AAT
model in guinea pigs. They showed an alleged preventive effects of HBOT in 14
out of 26 guinea pigs. Hu et al. reported that HBOT can reduce the noise
induced threshold shift and decrease cochlear damage during chronic noise
exposure in guinea pigs.
Intense noise produces mechanical damage to the cochlea, which directly leads
to disruption of the hair cell stereocilia. Pilgramm et al. demonstrated in an
animal model that 60 h after acoustic trauma, the number of inner ear sensory
cells that had suffered morphological damage was lower in the group receiving
HBOT than in the group without HBOT. Kuokkanen (1997)12 and (2000)13 showed a
lesser amount of threshold shift and fewer missing hair cells among rats that
were treated with HBOT following 60 shots (162 dB) with an assault rifle.
Colombari et al. found in an animal experiment with acute acoustic damage that
the number of injured cochlear outer hair cells decreased and that their
functionality improved after HBOT.

Clinically, it was shown that the combination therapy of HBOT and
corticosteroids has additional benefit to corticosteroids alone, and that early
treatment is key. However, in current practice patients have to undergo ten
days of HBOT and seven days of corticosteroid treatment (60 mg/day). In the
military, these ten days of treatment affect the employability of the soldier
and may have strategic consequences for decision making for military officers.
Therefore, the military is interested in reducing the amount of treatment days
for patients with AAT. It has already been shown that addition of two HBOT
sessions a day is as effective as one HBOT session a day in sudden
sensorineural deafness. However, no such studies exists for AAT. The aim of
this study is to investigate whether hyperbaric oxygen therapy twice-daily for
five days (HBOT5) is as effective in hearing loss recovery as hyperbaric oxygen
therapy once daily for ten days (HBOT10) for AAT.

This study has been transitioned to CTIS with ID 2024-517739-35-00 check the CTIS register for the current data.

The objective of this study is to investigate whether hyperbaric oxygen therapy
twice-daily for five days (HBOT5) is superior to hyperbaric oxygen therapy once
daily for ten days (HBOT10) in obtaining hearing loss recovery after AAT. This
will be determined by comparing audiometric outcomes at final follow-up.

As secondary objective, the amount military personnel recovering to the Dutch
Military Hearing Standards will be assessed using the Clinical Recovery Score,
which is based on the guidelines from the Committee on Hearing and Equilibrium
(see figure 3). Furthermore, the frequency and severity of adverse events (AEs)
will be assessed.

This study is a randomized superiority trial (1:1 allocation) comparing two
different treatment protocols of hyperbaric oxygen therapy (twice daily for 5
days [HBOT5] versus once daily for 10 days [HBOT10]). This design is chosen
because the standard of care in the Dutch military for acute acoustic trauma is
hyperbaric oxygen therapy once daily for 10 days with corticosteroids (60
mg/day for 7 days). However, practically the use of 10 days of HBOT hinders
employability of military personnel. Therefore, a randomized superiority trial
is performed. Included patients will be randomized to treatment with HBOT5
(intervention group) or HBOT10 (comparator). Patients will be treated at the
Department of Hyperbaric Medicine at the Amsterdam University Medical Centre,
Academic Medical Centre, Amsterdam, the Netherlands. Concomitant therapy with
corticosteroids 60 mg per day for 7 days is given in both groups (standard
practice). Patients will be seen by the hyperbaric physician before the start
of hyperbaric treatment. During hyperbaric sessions patients will be under
supervision of the hyperbaric physician and a separate appointment will be
scheduled at the end of treatment, at which side-effects of treatment will be
evaluated. Audiometry will be measured at presentation at the otolaryngology
clinic. Follow-up audiometry will be measured one month after the last HBOT
session.

The investigation treatment is hyperbaric oxygen therapy twice daily for five
days while the comparator treatment is hyperbaric oxygen therapy once daily for
ten days. Hyperbaric oxygen therapy will be performed in a multi-person
recompression chamber, where subjects breathed 100% oxygen via a built-in
breathing mask at a pressure of 240 kPa for 90 min, including three 5 min *air
breaks*.

HBOT is a very safe treatment method with very few serious adverse effects.
Adverse effects are often mild and reversible but could, potentially, be severe
and life threatening. As a consequence, strict precautions must be taken while
administering HBOT to avoid those complications. In addition, proper
installation and maintenance of a HBOT facility and adequate staffing with
specifically trained personnel is pivotal.

Barotrauma
Barotrauma is a general term to indicate injury to a tissue through the action
of differential pressures and it can occur in body areas where tissue and gas
interface, such as the middle ear, the sinuses and the lungs. Middle ear
barotrauma is the most commonly reported acute side effect of HBOT, and it was
reported to occur in 2% of patients. A prospective study reported that almost
one-fifth of all patients experienced some ear pain or discomfort related to
problems in middle ear pressure equalization, that can be resolved with
tympanostomy tubes, while visual otological examination confirmed barotraumatic
lesions in 3.8% of patients. Barotrauma can be avoided by careful patient
selection, excluding patient with contraindications for HBOT such as emphysema,
by patient education and by the termination of HBOT when early symptoms occur.
Pulmonary barotrauma is a potential problem mainly during the decompression
phase of HBOT since the volume of gas in the lungs increases due to the reduced
pressure and this extra volume needs to be breathed out. However, the
occurrence of this complication has only been reported in sporadic cases.

Any time that the environmental pressure is changed, all of the air spaces
within the body must remain in balance with these changes. If they do not,
discomfort will result. Study participants may experience this discomfort in
their ears, and very rarely, sinus space or tooth discomfort. If discomfort
occurs, study participants will be asked to advise a hyperbaric team member
immediately so that corrective action can be implemented. If a study
participant*s lungs do not ventilate adequately during pressure changes, he/she
may suffer a leak of pulmonary air into the chest, or into the bloodstream.
Such a leak could cause problems with the lungs such as a dry cough, chest pain
or burning, or central nervous system function such as confusion, altered
sensation, loss of consciousness, paralysis or even death. These complications
are rare, and every effort will be made to exclude all study participants who
may be at high risk of these side effects.

Effects on the brain
Hyperbaric oxygen may affect the brain and produce one or more signs or
symptoms, including muscle twitching, anxiety, confusion and dizziness. If the
situation is not corrected a generalized seizure may result (this occurs in
roughly 1 in 4000 treatments at 2.4 ATA). This is quickly corrected by removing
the oxygen. Again, this does not happen often, and every effort has been made
to exclude all study participants who may be at an increased risk of this side
effect.

Fire
Although increases in oxygen concentration can cause an increased risk of fire,
the hyperbaric chamber has been specially designed to minimize this risk. Only
cotton clothing and bedding, provided by chamber staff, will be used when study
participants are in the chamber to minimize this risk.

a. Level of knowledge about mechanism of action
Oxygen is considered as a drug and it can be administered easily under
normobaric conditions, but administering oxygen at pressures higher than 1 ATA
requires compression. This is usually done by having the patient breathe pure
oxygen or mixtures with other gases while being inside an airtight chamber in
which the pressure is greater than 1 ATA. Three primary mechanisms are believed
to be involved in the potential beneficial effects: bubble size reduction and
elimination in case of decompression sickness and gas embolism (commonly called
decompression illnesses or DCI), the achievement of hyperoxia in target organs,
and the potential enhancement of immune and healing mechanisms through the
correction of pre-existing hypoxia in target organs.