Dataset Information

High-Dose vs Standard-Dose Amoxicillin Plus Clavulanate for Adults With Acute Sinusitis: A Randomized Clinical Trial.

ABSTRACT:

Importance

Acute bacterial sinusitis is common, but currently recommended antibiotic treatment provides minimal benefit.

Objective

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.

Interventions

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.

Results

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.

Trial registration

ClinicalTrials.gov Identifier: NCT03431337.

SUBMITTER: Gregory J

PROVIDER: S-EPMC7988367 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe recommended treatment for acute bacterial sinusitis in adults, amoxicillin with clavulanate, provides only modest benefit.ObjectiveTo see if a higher dose of amoxicillin will lead to more rapid improvement.Design, setting, and participantsDouble-blind randomized trial in which, from November 2014 through February 2017, we enrolled 315 adult outpatients diagnosed with acute sinusitis in accordance with Infectious Disease Society of America guidelines.InterventionsStandard-dose (SD) immediate-release (IR) amoxicillin/clavulanate 875 /125 mg (n = 159) vs. high-dose (HD) (n = 156). The original HD formulation, 2000 mg of extended-release (ER) amoxicillin with 125 mg of IR clavulanate twice a day, became unavailable half way through the study. The IRB then approved a revised protocol after patient 180 to provide 1750 mg of IR amoxicillin twice a day in the HD formulation and to compare Time Period 1 (ER) with Time Period 2 (IR).Main measureThe primary outcome was the percentage in each group reporting a major improvement-defined as a global assessment of sinusitis symptoms as "a lot better" or "no symptoms"-after 3 days of treatment.Key resultsMajor improvement after 3 days was reported during Period 1 by 38.8% of ER HD versus 37.9% of SD patients (P = 0.91) and during Period 2 by 52.4% of IR HD versus 34.4% of SD patients, an effect size of 18% (95% CI 0.75 to 35%, P = 0.04). No significant differences in efficacy were seen at Day 10. The major side effect, severe diarrhea at Day 3, was reported during Period 1 by 7.4% of HD and 5.7% of SD patients (P = 0.66) and during Period 2 by 15.8% of HD and 4.8% of SD patients (P = 0.048).ConclusionsAdults with clinically diagnosed acute bacterial sinusitis were more likely to improve rapidly when treated with IR HD than with SD but not when treated with ER HD. They were also more likely to suffer severe diarrhea. Further study is needed to confirm these findings.Trial registrationClinicalTrials.gov Identifier: NCT02340000.

Project description:ObjectiveTo compare the effectiveness of amoxicillin-clavulanate versus amoxicillin for adults diagnosed with acute sinusitis (AS). A secondary objective compared antibiotic effectiveness in patients meeting risk criteria for treatment failure.MethodsA retrospective cohort study of adults diagnosed with AS prescribed amoxicillin ± clavulanate within Veterans Affairs emergency departments from 2012-2019 was conducted. The primary outcome was sinusitis-related return visits for amoxicillin versus amoxicillin-clavulanate. Secondary outcomes included 30-day infectious complications, gastrointestinal-related adverse events (AEs), and hospitalizations. Propensity-score matching and logistic regression models adjusted for potential confounders.ResultsA total of 89,627 AS patient visits were identified: 18,576 prescribed amoxicillin and 71,051 amoxicillin-clavulanate. Most patients were male (75,604; 84.4%) and afebrile (80,624; 91.7%). The propensity score-matched cohort comprised 17,929 amoxicillin and 42,294 amoxicillin-clavulanate patient visits. There was no difference in sinusitis-related return visits between amoxicillin (4.9%) and amoxicillin-clavulanate (5.1%) (adjusted odds ratio [OR], 0.96; 95% confidence interval [CI], 0.88, 1.04; P = 0.317). Infectious complications (amoxicillin [0.3%] vs amoxicillin-clavulanate [0.4%]); (adjusted OR, 0.78; 95% CI, 0.57, 1.07; P = 0.124) and hospitalization (amoxicillin [2.0%] vs amoxicillin-clavulanate [2.4%]); (adjusted OR, 0.92; 95% CI, 0.81, 1.04; P = 0.173) were not different. Gastrointestinal-related AEs were lower with amoxicillin (0.5%) relative to amoxicillin-clavulanate (0.7%); (adjusted OR, 0.67; 95% CI, 0.53, 0.86; P = 0.002). Comorbidity was the only guideline-recommended risk factor that was a significant predictor of infectious complications with respect to treatment (amoxicillin vs amoxicillin-clavulanate, OR, 0.63; 95% CI, 0.40 to 0.94; P = 0.022).ConclusionAmoxicillin demonstrated similar efficacy to amoxicillin-clavulanate for AS with fewer gastrointestinal-related AEs. Amoxicillin is a viable option in adults with AS meeting criteria for antibiotic therapy.

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Project description:ImportanceA lower dose of intravenous alteplase appears to be a safer treatment option than the standard dose, reducing the risk of symptomatic intracerebral hemorrhage. There is uncertainty, however, over how this effect translates into an overall clinical benefit for patients with acute ischemic stroke (AIS).ObjectiveTo assess whether older, Asian, or severely affected patients with AIS who are considered at high risk of thrombolysis may benefit more from low-dose rather than standard-dose alteplase treatment.Design, setting, and participantsThis study is a prespecified secondary analysis of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), an international, randomized, open-label, blinded, end-point clinical trial of low-dose vs standard-dose intravenous alteplase for patients with AIS. From March 1, 2012, to August 31, 2015, a total of 3310 patients who had a clinical diagnosis of AIS as confirmed by brain imaging and who fulfilled the local criteria for thrombolysis treatment were included in the alteplase-dose arms. Patients were randomly assigned to receive low-dose (0.6 mg/kg; 15% as bolus and 85% as infusion over 1 hour) or standard-dose (0.9 mg/kg; 10% as bolus and 90% as infusion over 1 hour) alteplase. Of the 3310 randomized patients, 13 patients were excluded for missing consent, mistaken randomization, and duplicate randomization numbers. This secondary analysis was conducted between May 1, 2016, and April 28, 2017.Main outcomes and measuresThe primary end point was a poor outcome defined by the combination of death and any disability as scored by the modified Rankin Scale (scores range from 2 to 6, with the highest score indicating death) at 90 days.ResultsOf the 3297 patients included in the analysis, 1248 (37.9%) were women, and the mean (SD) age was 67 (13) years. No significant differences in the treatment effects were observed between low- and standard-dose alteplase for poor outcomes (death or disability) by age, ethnicity, or severity (all P > .37 for interaction). Similarly, the treatment effects of low- vs standard-dose alteplase on function outcome (ordinal shift of the modified Rankin Scale) in Asians (odds ratio, 1.05; 95% CI, 0.90-1.22) was consistent with non-Asians (odds ratio, 0.93; 95% CI, 0.76-1.14) (P = .32 for interaction). There were generally consistent reductions in rates of symptomatic intracerebral hemorrhage with low-dose alteplase, although this reduction was not statistically significant by age, ethnicity, or severity.Conclusions and relevanceThis analysis found that the effects of low-dose alteplase were not clearly superior to the effects of standard-dose alteplase on death or disability in key demographic subgroups of patients with AIS. Further investigation is required to identify patients with AIS who may benefit from low-dose alteplase.Trial registrationclinicaltrials.gov Identifier: NCT01422616.

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