Trial Outcomes & Findings for Efficacy of Antibiotics in Children With Acute Sinusitis: Which Subgroups Benefit? (NCT NCT02554383)

Children determined to be eligible for the study and whose parents agreed to participation were randomized to one of two treatments arms. At each site of enrollment, within stratum defined by the presence/absence of colored (yellow or green) nasal discharge, children were randomized 1:1 in blocks of four to receive either twice daily amoxicillin-clavulanate or matching placebo. The analyses of study data were based on the randomized treatment assignment.

Efficacy of Antibiotics in Children With Acute Sinusitis: Which Subgroups Benefit?

The Pediatric Rhinosinusitis Symptom Scale (PRSS) is a 8 item scale assessing symptoms of sinusitis. Parents are asked how their child has been doing over the last 24 hours by rating each of 8 symptoms - stuffy nose, runny nose, daytime cough, tiredness, irritability, trouble breathing through the nose, nighttime cough \& trouble sleeping - as none, almost none, a little, some, a lot \& an extreme amount with respective scores of 0, 1, 2, 3, 4 \& 5. The 8 ratings were summed to obtain a PRSS score. Scores ranged from 0-40. Higher scores indicate greater severity. The parent completed the scale on Day 1 (enrollment) \& electronically on diaries evenings Days 2-11. Pathogens cultured were Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.

The Pediatric Rhinosinusitis Symptom Scale (PRSS) is a 8 item scale assessing symptoms of sinusitis. Parents are asked how their child has been doing over the last 24 hours by rating each of 8 symptoms - stuffy nose, runny nose, daytime cough, tiredness, irritability, trouble breathing through the nose, nighttime cough \& trouble sleeping - as none, almost none, a little, some, a lot \& an extreme amount with respective scores of 0, 1, 2, 3, 4 \& 5. The 8 ratings were summed to obtain a PRSS score. Scores ranged from 0-40. Higher scores indicate greater severity. The parent completed the scale on Day 1 (enrollment) \& electronically on diaries evenings Days 2-11. Nasal discharge, either yellow or green, was considered colored.

The Pediatric Rhinosinusitis Symptom Scale (PRSS) is a 8 item scale assessing symptoms of sinusitis. Parents are asked how their child has been doing over the last 24 hours by rating each of 8 symptoms - stuffy nose, runny nose, daytime cough, tiredness, irritability, trouble breathing through the nose, nighttime cough \& trouble sleeping - as none, almost none, a little, some, a lot \& an extreme amount with respective scores of 0, 1, 2, 3, 4 \& 5. The 8 ratings were summed to obtain a PRSS score. Scores ranged from 0-40. Higher scores indicate greater severity. The parent completed the scale on Day 1 (enrollment), electronically evenings Days 2-11 \& at the follow-up visit. If, compared to the Day 1 score, there was \>20% increase at any time, decrease \<2 on Day 3, \<20% decrease on Day 4, \<20% decrease on 2 consecutive occasions Days 5-11 or \<50% decrease at follow-up, then criterion for treatment failure (TF) was met. Multiple imputation was used when data was insufficient to assess TF.

AOM is an infection of the middle ear marked by acute symptoms and a bulging tympanic membrane. Its diagnosis coincided with receipt of a systemic antibiotic. Systemic antibiotics include Amoxicillin, Amoxicillin-clavulanate, Azithromycin, Bacillin L-A, Cefdinir, Clindamycin, Doxycycline, Levofloxacin, Ofloxacin \& Sulfamethoxazole-Trimethoprim. Start and stop dates were recorded.

Systemic antibiotics include Amoxicillin, Amoxicillin-clavulanate, Azithromycin, Bacillin L-A, Cefdinir, Clindamycin, Doxycycline, Levofloxacin, Ofloxacin \& Sulfamethoxazole-Trimethoprim. Start and stop dates were recorded. The antibiotic received is exclusive of the study product assigned at enrollment.

The monitoring of adverse events (AEs), i.e. diarrhea or generalized rash, began on Day 1 (enrollment) and continued through Day 23 (the follow-up visit). Diarrhea was the occurrence of 3 or more watery stools on one day or 2 watery stools on each of 2 consecutive days. Parents recorded in daily diaries, Days 1-11, information regarding the occurrence of diarrhea. Additionally, parents were asked at the follow-up visit if their child had diarrhea while on study product.

Compliance, expressed as a percentage, is the total number of doses taken divided by the total number of expected doses. The child is considered compliant if he/she has received at least 70% of the study medication. The parent completed diaries evenings Days 2-11. The diaries included yes/no questions - (1) did your child take the study medication last night and (2) did your child take the study medication this morning? The total number of doses taken was calculated based on the responses to question (1), and accounted for the dose dispensed at enrollment when enrollment was 1pm or earlier on Day 1. The total of expected doses was determined from the responses to questions (1) and (2), and accounted for scenarios in which the child was taken off the study medication by the clinician. In some cases, due to incomplete diaries the information was insufficient to declare a child either compliant or not compliant.

The nonsusceptible pathogens considered are penicillin-intermediate and penicillin-resistant Streptococcus pneumoniae (SPN) and ß-lactamase-positive Haemophilus influenzae (NTHi). Susceptibility to penicillin was defined as follows: susceptible as a minimum inhibitory concentration (MIC) of \<=0.06 μg/mL; intermediate as an MIC of greater than 0.06 to less than 2 μg/mL; and resistant as an MIC of \>=2 μg/mL. A nasopharyngeal specimen for bacterial culture was obtained at the time of the follow-up visit, occurring between study days 11 and 23.