A randomised clinical trial indicate additional amoxicillin did not benefit adults receiving amoxicillin and clavulanate for acute sinusitis, researchers at Albany Medical College, Stony Brook University Hospital and the Albany College of Pharmacy and Health Sciences, report.
In the double-blind, comparative effectiveness trial, adult patients at Albany Medical Centre in New York who had symptoms of acute sinusitis were randomly allocated to two treatment groups: the standard treatment of 875 milligrams (mg) of amoxicillin and 125 mg of clavulanate plus a placebo tablet, or a high-dose treatment of 875 mg of amoxicillin and 125 mg of clavulanate plus 875 mg of amoxicillin twice a day for 7 days.
The purpose was to replicate a previous trial in which an unplanned subgroup analysis had found that higher-dose amoxicillin might provide a benefit.
The primary efficacy outcome was the percentage of patients who reported a Global Rating of Improvement (GRI) score of 5 or 6 ("a lot better" or "no symptoms") after 3 days of treatment. The primary safety outcome was a score of 3 ("severe") for diarrhoea at day 3 or 10. A total of 157 patients, out of a projected 240, were enrolled in the study, with 79 receiving the standard dose and 78 the high dose; 9 and 12 patients, respectively, withdrew or were lost to follow-up before assessment of the primary outcome.
An unplanned interim analysis prompted by COVID-19 restrictions found that at day 3, a total of 31 of 70 patients in the standard-dose group (44.3%) reported a score of 5 or 6, compared with 24 of 66 (36.4%) in the high-dose group, for a difference of -7.9% (95% CI, -24.4% to 8.5%). At that point, the study was stopped for futility. Evaluation of safety data showed diarrhoea was common in both groups at day 3, with 40.8% in the standard-dose group and 43.1% in the high-dose group reporting any diarrhoea. Severe diarrhoea was reported in 7.0% of the standard-dose patients and 7.7% of the high-dose group.
The study authors say the finding is disappointing, since the standard treatment has been found to provide only minimal benefits for acute sinusitis.
High-Dose vs Standard-Dose Amoxicillin Plus Clavulanate for Adults With Acute Sinusitis: A Randomized Clinical Trial
Jennifer Gregory; Bichtram Huynh; Brittany Tayler; Chaitali Korgaonkar-Cherala; Gina Garrison; Ashar Ata; Paul Sorum
Published in JAMA Network Open on 23 March 2021
Acute bacterial sinusitis is common, but currently recommended antibiotic treatment provides minimal benefit.
To confirm the previous finding that high-dose amoxicillin plus clavulanate (with double the amount of amoxicillin) may be superior to standard-dose amoxicillin plus clavulanate in adults.
Design, Setting, and Participants
This double-blind, comparative-effectiveness randomized clinical trial was conducted from February 26, 2018, through May 10, 2020, at the academic primary care internal medicine and pediatrics practice of Albany Medical Center, located in Cohoes, New York. Participants included adults aged 18 years or older who were prescribed amoxicillin plus clavulanate for acute bacterial sinusitis diagnosed in accordance with the Infectious Diseases Society of America guidelines.
Amoxicillin 875 mg with clavulanate 125 mg plus either placebo (standard dose) or amoxicillin 875 mg (high dose) twice a day for 7 days.
Main Outcomes and Measures
The primary efficacy outcome was a global rating of “a lot better” or “no symptoms” at the end of 3 days of treatment using a Global Rating of Improvement scale, with outcomes ranging from 1 (a lot worse) to 6 (no symptoms). The primary adverse effect outcome was severe diarrhea at 3 or 10 days after the start of treatment.
At an unplanned interim analysis prompted by COVID-19 restrictions, 157 of a projected 240 participants had been enrolled (mean age, 48.5 [range, 18.7-84.0] years; 117 women [74.5%]), with 79 randomized to the standard dose and 78 to the high dose; 9 and 12, respectively, withdrew or were lost to follow-up before the assessment of the primary outcome. At day 3, 31 of 70 participants (44.3%) in the standard-dose group reported a global rating of “a lot better” or “no symptoms,” as did 24 of 66 (36.4%) in the high-dose group, for a difference of −7.9% (95% CI, −24.4% to 8.5%; P = .35). The study was, therefore, stopped for futility. Diarrhea was common in both groups by day 3, with any diarrhea reported in 29 of 71 participants (40.8%) receiving the standard dose and 28 of 65 (43.1%) receiving the high dose and severe diarrhea reported in 5 of 71 (7.0%) and 5 of 65 (7.7%), respectively.
Conclusions and Relevance
The results of this randomized clinical trial suggest that adults treated for clinically diagnosed acute sinusitis did not appear to benefit from taking high-dose compared with standard-dose amoxicillin plus clavulanate.
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