Oral steroids for resolution of otitis media with effusion in children (OSTRICH): a double-blinded, placebo-controlled randomised trial

Clinical Question

In pediatric patients with otitis media with effusion, do oral steroids compared to the standard care of otitis media reduce hearing loss due to otitis media effusion?

Bottom Line

Short term oral steroid use in children diagnosed with otitis media with effusion who experienced hearing loss does not significantly aid in improving hearing loss.

Major Points

Otitis media with effusion affects roughly 80 percent of children by the time they are 4 years of age, and the most prominent complication in these children is hearing loss. The standard treatment for pediatric patients with hearing loss due to otitis media with effusion is surgery after a watchful waiting period of 3 months. The surgery involves the insertion of ventilation tubes through the tympanic membrane.

This study was a randomized control trial (RCT) to assess if oral steroids compared to standard treatment of otitis media with effusion reduces hearing loss. The study itself included pediatric patients ages 2-8 years old with otitis media with effusion. Patients were randomized to receive the treatment (prednisolone) or a placebo. Oral steroids are a relatively cost-effective method compared to standard treatment. Using intention-to-treat analysis, the study revealed that oral corticosteroids were not effective at improving/preventing hearing loss from otitis media with effusion, per the primary outcome which measured acceptable hearing at 5 weeks following randomisation. However, the secondary outcomes of acceptable hearing in the 5 weeks-6 months and 5 weeks-12 months windows following randomisation did show a significant increase in acceptable hearing in the children receiving oral corticosteroids.

The article notes uncertainty in their cost-effectiveness analysis. The researchers also speculate that because of some children spontaneously recovering, there may have been insufficient power to demonstrate a significant primary outcome. In terms of positive internal criticism, the researchers believe their methods made this RCT the most rigorous trial within the literature assessing oral steroids in children diagnosed with otitis media with effusion.

Guidelines

The article we reviewed draws from both US and UK guidelines. Current US clinical practice guidelines (“Otitis Media with Effusion” from the American Academy of Otolaryngology Head and Neck Surgery, updated in 2016) clarify the standard of care for pediatric patients with acute otitis media with effusion and (possible) hearing loss secondary to the infection. This includes a watchful waiting period of three months from the date of the effusion onset or diagnosis. Standard surgical treatment is not utilized during this watchful waiting period. The UK Guidelines for treating the same condition utilizes the same watchful waiting criteria and surgical intervention. This guideline comes from the National Institute for Health and Care Excellence (NICE) Clinical Practice Guideline on Surgical Management of Otitis Media with Effusion in Children.

Design

• The study was a randomized controlled trial (RCT) which was double-blinded and controlled with a standard of care group.
• Number of patients randomized: 389 Patients (of 1018 screened) were randomized.
• Experimental arm: 200 of the randomized patients received an oral steroid.
• Standard: 189 of the randomized patients received a placebo.
• Setting: The patients screened were from 20 different ENT outpatient departments located in England and Wales. The study also included pediatric audiology and audiovestibular medicine outpatient departments.
• Enrollment: Patients were enrolled from March 20th, 2014 to April 5th, 2016.
• Mean follow-up: Follow-ups occurred at 5 weeks, 6 months, and 12 months.
• Analysis: An intention-to-treat analysis was performed.
• Outcomes: Audiometry-confirmed acceptable hearing at the first follow-up (5 weeks) was the primary outcome, while audiometry-confirmed acceptable hearing at the 6-month and 12-month follow-ups were secondary outcomes.

Population

Inclusion Criteria

• Children ages 2-8 years old
• Diagnosis of otitis media with effusion
• Symptoms for at least 3 months
• Confirmed bilateral hearing loss

Exclusion Criteria

• Hearing loss that did not meet the inclusion criteria (bilateral hearing loss)
• Insufficient hearing loss
• Congenital disorders
• Genetic disorders
• Major comorbidities
• Younger than 2 years of age
• Older than 8 years of age

Baseline Characteristics

• Demographics
• Medical History
• Medication use
• Audiometry
• Degree of Hearing Loss
• Right Ear
• Left Ear
• Tympanometry
• Otoscopy of both ears
• Insertion of ventilation tubules
• Daily symptoms
• Adverse effects
• Serious adverse events
• Withdrawals
• Resource use
• Functional health status
• Health Related quality of life

The baseline characteristics did not include any clinically relevant differences between the experimental group and the placebo group. The results listed percent of patients with the baseline characteristics and all were very similar.

Interventions

The intervention studied was the use of oral corticosteroids (versus standard of care). The steroid therapy given was a 7-day course of prednisolone solution. Children 2-5 Y/O took prednisolone 20 mg by mouth daily for 7 days, and children 6-8 Y/O took prednisolone 30 mg by mouth daily for 7 days.

Outcomes

Primary Outcomes

Audiometry-confirmed acceptable hearing at 5 weeks after randomisation, where the 7-day course of prednisolone/placebo pack would have since been completed. There was no significant increase in acceptable hearing with the group who received oral corticosteroids compared to the control group

CI 0.88-2.11

Secondary Outcomes

Audiometry-confirmed acceptable hearing at 6 months and 12 months after randomisation. There was a significant increase in acceptable hearing within the group receiving oral corticosteroids from the 5 weeks to 6 months interval and the 5 weeks to 12 months interval

P=<0.001 for both intervals analyzed

Subgroup Analysis

The following are the categories the study used for subgroup analyses:

• Age (2-5, 6-8)
• Atopy (positive/negative history)
• Recent antibiotic use (positive/negative for antibiotic use in last month)
• Previous OSTRICH diagnosis before this episode (positive/negative)
• Symptom duration (before or greater/equal to 12 months)
• History of tonsillectomy or adenoidectomy (positive/negative)
• Presence/absence of smokers in child’s household
• Season recruited (summer, fall, winter, spring)
• Deprivation by quintiles

The study analyzed these predetermined subgroups within the study. The effects of treatment did not differ between the subgroups except for people who received antibiotics for an ear-related issue within the past month. No subgroup stood out as having an increased significant benefit from steroid use.

Adverse Events

Table 5 within the article shows all of the adverse events during the trial. When comparing the control and experimental group, there was no significant difference in adverse events. For each adverse event, less than 10 cases occurred for both groups. The adverse events that occurred were characterized as respiratory tract infections, digestion, behavioral, and “other.”

Criticisms

Internal Criticisms: The article notes uncertainty in their cost-effectiveness analysis. More specifically, the researchers noted, “Our evidence does not support a one-week course of oral steroids as a cost effective option for children aged 2–8 years with otitis media with effusion, but there is considerable uncertainty in our cost-effectiveness estimates.”

The researchers also speculate that because of some children spontaneously recovering, there may have been insufficient power to demonstrate a significant primary outcome.

In terms of positive internal criticism, the researchers believe their methods made this RCT the most rigorous trial within the literature assessing oral steroids in children diagnosed with otitis media with effusion.

External Criticisms: Researcher Michael E. Pichichero wrote a review article titled, “Helping children with hearing loss from otitis media with effusion,” which dedicated several paragraphs to explaining/criticizing this RCT. Although he commended the RCT for being the largest trial to date regarding improvement of hearing loss in children diagnosed with otitis media with effusion, he noted two limitations. One was that the age range of children 2-8 Y/O was not broad enough, as children aged 6 months to 2 Y/O have an even higher incidence of otitis media with effusion in general. His second noted limitation was that most children in the study had been diagnosed with having otitis media with effusion over 12 months before the RCT (despite the inclusion criteria of having otitis media with effusion for longer than 3 months). Thus, he predicts only one week of oral steroids would not been enough to see a true benefit in these patients, as effusion is known to become more viscous as time increases (whereas the same intervention may have shown significant improvement in an OSTRICH patient diagnosed close to 3 months prior to the RCT).

Funding

This study was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme. In the text, the study clarified that the funder had no roles in the study other than funding.

Further Reading

1. Francis NA, Cannings-John R, Waldron CA, Thomas-Jones E, Winfield T, Shepherd V, Harris D, Hood K, Fitzsimmons D, Roberts A, Powell C, Gal M, Butler CC. (2018). Oral steroids for resolution of otitis media with effusion in children (OSTRICH): a double-blinded, placebo-controlled randomised trial. Lancet (London, England), 392(10147), 557–568. doi:10.1016/S0140-6736(18)31490-9.

2. Pichichero ME (2018). Helping children with hearing loss from otitis media with effusion. Lancet (London, England), 392(10147), 533–534. Doi: 10.1016/S0140-6736(18)31862-2.