EBQ:TOAST Trial

Complete Journal Club Article

Hayward GN, Hay AD, Moore MV, Jawad S, Williams N, Voysey M, Cook J, Allen J, Thompson M, Little P, Perera R, Wolstenholme J, Harman K, Heneghan C. "Effect of Oral Dexamethasone Without Immediate Antibiotics vs Placebo on Acute Sore Throat in Adults: A Randomized Clinical Trial.". JAMA. 2017. 317(15):1535-1543.
PubMed Full text

Clinical Question

• Does the use of oral dexamethasone in acute pharyngitis in the absence of antibiotics significantly increase the rate of resolution of symptoms at 24 hours?

Conclusion

• The use of single dose oral dexamethasone compared with placebo did not increase the proportion of patients with resolution of symptoms at 24 hours. However, there was a significant difference at 48 hours

Major Points

• Corticosteroids may be beneficial in the treatment of acute pharyngitis as they are in upper respiratory infections but the effect is likely more pronounced in those with severe symptoms.

Study Design

• Multicenter, double-blinded, placebo-controlled, parallel group randomized trial
• England, 42 family practice centers
• 576 adult patients with acute pharyngitis, not require antibiotics
• study group given single dose of 10mg dexamethasone or placebo.

Population

Inclusion Criteria

• ≥18 years of age
• Sore throat/odynophagia thought to be inefective in origin
• Symptom onset in the last 7 days
• No need for antibiotic treatment
• Consent to participate and willingness to keep a symptom journal.

Exclusion Criteria

• Pregnant/breast feeding
• Use of inhaled or oral corticosteroids within the last month
• History of tonsillectomy in the last month
• Use of antibiotics in the last 14 days
• Alternative Diagnosis
• Immunodeficiency
• Hospital admission
• Antibiotics needed
• Allergy to dexamethasone

Interventions

• 10mg oral dexamethasone or identical placebo

Outcomes

• 565 patients were eligible
  • 288 given dexamethason
  • 277 given placebo
• Median Age of 34
• 75.2% women
• 100% completed intervention

Primary Outcome

• Proportion of patients experiencing complete resolutino of symptoms at 24 hours
  • Dexamethasone 22.6%
  • Placebo 17.7%
  • Risk Difference (95% C.I.) 4.7% (-1.8-11.2)
  • RR (95% CI): 1.28 (0.92-1.78)
  • P value 0.14

Secondary Outcomes

• Complete Resolution in 48 hours
  • 35.4% Dexamethasone
  • 27.1% Placebo
  • Risk Difference 8.7% (1.2-16.2)
  • RR 1.31 (1.02-1.68)
  • P Value 0.03
• Duration of moderately bad symptoms (Based on Likert scale)
• Visual analog scales
• Health care attendance

No statistical difference in the remainder of secondary outcomes

Criticisms & Further Discussion

Strengths

• Multicenter, double-blind, placebo-controlled, parallel group randomized trial
• Sample size large enough to find 18% increase in resolution with 90% power
• Primary outcome was collected from 93.6% of participants

Limitations

• Excluding patients receiving antibiotics may have excluded a population that would have benefited more from treatment
• No children were studied
• Primary outcome was not well validated
• Study unable to detect difference less than 18% due to underpower

Discussion

• Although there was no difference in primary outcome, there was significant difference at 48 hours.
  • Gives a NNT of 12
• The study was underpowered to detect differences less than 18%
  • A larger study could potentially find a more significant difference
• Patients may not have had symptoms severe enough to benefit from treatment
  • Patients who needed antibiotics were excluded
  • Generally speaker, sicker patients, would likely benefit more from dexamethasone treatment
    • Other studies have supported this in the past
• Study was done at family care centers
  • Potentially the patient population may not represent what is seen in the ED as their symptoms may not have been as "severe" or emergent.

External Links

ISRCTN Registry

Funding

• National Institute for Health Research (UK)