Short Term Relief of Eustachian Tube Dysfunction and Serous Otitis Media Using Intranasal Steroid Sprays
|First Received Date ICMJE||January 18, 2006|
|Last Updated Date||July 20, 2011|
|Start Date ICMJE||September 2005|
|Primary Completion Date||February 2009 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Complete Normalization [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
Type A tympanogram in both ears
|Original Primary Outcome Measures ICMJE
|Change History||Complete list of historical versions of study NCT00279916 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Complete Normalization, Including Treatment Failures [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
Type A tympanogram and not taking antibiotics, oral decongestants, nasal spray or combo
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Short Term Relief of Eustachian Tube Dysfunction and Serous Otitis Media Using Intranasal Steroid Sprays|
|Official Title ICMJE||Short Term Relief of Eustachian Tube Dysfunction and Serous Otitis Media Using Intranasal Steroid Sprays: a Randomized Placebo-controlled Study|
|Brief 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).|
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.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 3|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Study Arm (s)||
|Publications *||Gluth MB, McDonald DR, Weaver AL, Bauch CD, Beatty CW, Orvidas LJ. Management of eustachian tube dysfunction with nasal steroid spray: a prospective, randomized, placebo-controlled trial. Arch Otolaryngol Head Neck Surg. 2011 May;137(5):449-55. doi: 10.1001/archoto.2011.56.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||March 2009|
|Primary Completion Date||February 2009 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||Patients with serous otitis media and/or negative middle ear pressure will be considered for enrollment.|
|Ages||6 Years and older (Child, Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00279916|
|Other Study ID Numbers ICMJE||103-04, XRG5029C/4008|
|Has Data Monitoring Committee||Yes|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||Laura J Orvidas, MD, Mayo Clinic|
|Study Sponsor ICMJE||Mayo Clinic|
|Collaborators ICMJE||Aventis Pharmaceuticals|
|Information Provided By||Mayo Clinic|
|Verification Date||July 2011|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP