Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00279916 |
| Other study ID # |
103-04 |
| Secondary ID |
XRG5029C/4008 |
| Status |
Completed |
| Phase |
Phase 3
|
| First received |
January 18, 2006 |
| Last updated |
July 20, 2011 |
| Start date |
September 2005 |
| Est. completion date |
March 2009 |
Study information
| Verified date |
July 2011 |
| Source |
Mayo Clinic |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
United States: Institutional Review Board |
| Study type |
Interventional
|
Clinical Trial Summary
We hypothesize that intranasal steroid application will have a beneficial therapeutic effect
in adults with regard to resolution of SOM and/or NMEP as compared to placebo. We further
hypothesize that the rate of spontaneous short-term resolution of OME in adults treated with
placebo will be relatively low (minority of patients).
Description:
The term serous otitis media (SOM) generally refers to an accumulation of fluid within the
middle ear space in the absence of signs indicating acute infection. Other frequently
encountered descriptions of this condition include otitis media with effusion, secretory
otitis media, non-suppurative otitis media, mucoid otitis media, or "glue ear." Commonly,
OME results in a conductive hearing loss due to restriction of tympanic membrane mobility as
well as alteration of the acoustic properties of the middle ear space and round window. In
addition to hearing loss, adults with this condition may complain of aural fullness or have
an increased risk of acquiring acute otitis media.
Negative middle ear pressure is a relatively common finding in adults that often is a
precursor to the development of SOM. At times, NMEP may be great enough to induce medial
retraction of the tympanic membrane and/or draping over the ossicles—often referred to as
tympanic membrane atelectasis. This condition may be seen with or without a middle ear
effusion. As with SOM, NMEP also has its own unique effect on the acoustic properties of the
middle ear resulting in conductive hearing loss. Retraction of the tympanic membrane may
ultimately lead to the formation of middle ear adhesions (adhesive otitis media) and/or
acquired cholesteatoma.
Both SOM and NMEP are elements of a clinical spectrum that results, in part, from
dysfunction of the eustachian tube. The properly functioning eustachian tube affords
ventilation of the middle ear cavity that is necessary to prevent the development of a
negative pressure gradient which results from middle ear mucosal gas absorption. In turn, as
negative pressure develops within the middle ear, a serous transudate may form and the
tympanic membrane may retract. Other functions of the eustachian tube include acting as an
outlet for clearance of glandular secretions and/or debris into the nasopharynx as well as
forming a protective barrier (when collapsed) from ascending nasopharyngeal pathogens or
barotrauma.
Eustachian tube dysfunction (ETD) in the setting of SOM and NMEP primarily refers to an
absent or inadequate ability to open the eustachian tube. The most common cause of
persistent ETD in adults is rhinitis (allergic rhinitis, vasomotor rhinitis, or mixed
rhinitis). In some instances, it is hypothesized that the severity of rhinitis might be
subclinical in terms of causing typical symptoms (rhinorrhea, nasal obstruction, anosmia),
yet still of sufficient severity in the region of the eustachian tube orifice as to cause
ETD. Most attempts at addressing ETD medically for patients with rhinitis have been aimed at
decreasing mucosal swelling. Although many varied therapeutic interventions have been
devised to treat ETD, no single therapy has been proven clearly efficacious and/or gained
widespread acceptance.
In 2001, van Heerbeek et al1 reviewed the results reported for many of these interventions
in animal models and humans. Medical interventions reviewed included topical and aerosolized
surfactant, systemic beta and alpha adrenoreceptor agonists (among other decongestants),
systemic antihistamines, and other agents aimed at improving mucociliary function. Although
some of these interventions (surfactant and decongestants) have shown positive effects in
some studies, there remains a disagreement in results between various reports and, in
particular, a lack of prospective randomized double-blind placebo-controlled studies. The
authors concluded that there was not sufficient data to clearly support any particular
therapy in humans at that time. Of particular note, a separate report by van Heerbeek also
demonstrated no effect of single dose topical application of a nasal decongestant (alpha
receptor agonist) on ETD in children in a randomized, double-blinded, placebo-controlled
study using sophisticated measures of eustachian tube function.
Surgical interventions aimed at treating ETD have included PE tube placement and/or
adenoidectomy. Multiple studies have reported no improvement of underlying ETD after
pressure-equalization tube placement—despite improvement or resolution of SOM and/or
tympanic membrane atelectasis. In fact, some authors have reported worsened eustachian tube
function following pressure-equalization tube placement. Studies relating to adenoidectomy
have dealt with the pediatric population and, in general, have also failed to demonstrate an
improvement in ETD.
Recently, Silverstein reported preliminary results of a non-controlled study of direct
application of dexamethasone to the tympanic-side orifice of the eustachian tube via a wick
passed through a pressure-equalization tube. Data on this limited study of a small cohort of
patients indicated a positive effect in terms of resolving patient complaints of aural
fullness and eventually converting their tympanograms to type A.
Some clinicians have suggested that nasal steroid sprays may have a role in dealing with ETD
causing SOM and NMEP. Specific attempts to address the effect of nasal steroid application
on ETD are very limited. Most studies that exist do indeed suggest a benefit in children,
but have generally been too limited in scope to definitively demonstrate statistically
significant benefits. To our knowledge, no such studies exist that deal with adult patients.
We are only aware of 4 studies that address treatment of SOM with nasal steroids in
children; we are aware of no studies that specifically deal with NMEP.
In 1982, Shapiro studied 45 children with both allergic rhinitis and SOM prospectively to
compare aerosolized nasal dexamethasone to placebo. Normal middle ear pressures were
encountered more frequently in the group treated with dexamethasone at 1 and 2 week
intervals suggesting a benefit in the short-term; no statistical significance was found
between the two groups when the study ended at week 3. The authors concluded that
aerosolized dexamethasone had some therapeutic efficacy, but recommended that treatment be
limited to 2 weeks.
That same year, Lildholdt and Korthol reported data on 70 children treated with either
intranasal beclomethasone or placebo and found no statistical difference in resolution of
effusion at 4 weeks. The authors concluded that there was no active therapeutic effect on
the studied population.
In 1998 Tracy evaluated the benefit of adding intranasal steroids to an oral antibiotic
regimen vs oral antibiotics plus placebo vs oral antibiotics alone in a study group of 61
children and found more frequent resolution of effusions as noted by otoscopy, tympanometry,
and a symptom questionnaire with steroid therapy at 1 and 2 months. The benefit was also
noted at 3 months but it did not reach statistical significance. The authors concluded that
intranasal steroids might be a useful adjunct to prophylactic antibiotic therapy.
Finally, in 2002, a similar study by Karlidag demonstrated an 8 week resolution rate of SOM
in children of 39% on a regimen of antibiotics and nasal steroids as compared to a rate of
24% with antibiotics alone and 5% with no treatment. Roughly 20 children were in each
treatment arm. However, the study sample was too small to be of statistical significance.
It should again be noted that these studies were all based on pediatric subjects. Many
believe that the mechanics of ETD differs between children and adults. Given the variations
in anatomy and other key immunologic factors between adults and children with SOM, it is
difficult to know what application the above limited pediatric studies might have in an
adult patient population.
Newer intranasal steroid preparations are generally safe with relatively few side effects as
demonstrated in large studies dealing with allergic rhinitis.
Due to the lack of a single accepted medical intervention to deal with ETD and the general
benign nature of this condition, it is common practice for some physicians to take a "wait
and see" initial approach when this clinical entity is encountered in lieu of prescribing
unproved medications. It is generally accepted that some patients with NMEP and/or SOM will
undergo spontaneous resolution of symptoms, yet the exact resolution rates are not clearly
defined.
