More recently, the UK National Institute for Health Research issued a Health Technology Assessment (HTA) report highlighting the findings of CAP-IT (Community-Acquired Pneumonia: a protocol for a randomized, controlled Trial), a randomized, double-blind, placebo-controlled, factorial, noninferiority trial that was conducted in emergency departments, assessment/observation units, and inpatient wards in the UK and Ireland.
CAP-IT examined the duration and dose of amoxicillin in the treatment of uncomplicated CAP in children older than age 6 months who weighed 6 to 24 kg for whom amoxicillin was the antibiotic to be administered upon discharge. HTA research is undertaken when some evidence is already present for a given intervention but needs to be compared with the current standard intervention to determine what approach works best.
The primary objective of the CAP-IT trial was twofold: to determine if a 3-day course of amoxicillin was noninferior to a 7-day course of another antibiotic that was clinically indicated for respiratory tract infections in the 4 weeks after randomization (up to Day 28) and to evaluate whether a lower dose of amoxicillin was noninferior to high-dose amoxicillin in CAP. Secondary objectives were to determine the impact of lower-dose and shorter-duration amoxicillin on antimicrobial resistance, severity and duration of CAP symptoms, and presence of adverse drug events.
Exclusion criteria included underlying chronic diseases that can increase the risk of developing CAP, such as sickle cell anemia immunoincompetence; chronic lung disease; cystic fibrosis; penicillin allergy; complicated pneumonia; or bilateral wheezing without focal chest signs.
Amoxicillin was administered as either a low-dose suspension (35-50 mg/kg/day) or a high-dose suspension (70-90 mg/kg/day) for 3 to 7 days upon discharge from the hospital.
Children were randomized to one of four groups based on dose and duration: low dose, short duration; low dose, long duration, high dose, short duration; or high dose, long duration. They were also evaluated to determine whether they had received nontrial antibiotics in the hospital prior to enrollment in the clinical trial.
The primary outcome was the use of any clinically indicated systemic antibiotic for a respiratory tract infection (including CAP), other than amoxicillin, within 4 weeks of randomization to CAP-IT. Secondary outcomes focused on the development of resistant S pneumoniae, severity and duration of CAP symptoms, adherence, and the occurrence of adverse events, especially serious adverse events.
Investigators found that of the 814 participants, 12.5% of the study population met the primary endpoint, including 12.6% in the lower-dose arm and 12.4% in the higher-dose arm and 12.5% each in the shorter-duration and longer-duration arms. The upper 90% confidence limit for both comparisons (low-high, short-long) was less than the noninferiority margin of 8%, indicating noninferiority for the dose and duration comparisons.
The only symptom for which a difference was observed was cough, which resolved faster in the longer-duration group than the shorter-duration group (10 days vs. 12 days, respectively). This cough affected sleep. The only difference in adverse events between the groups was that slightly more rash was observed after baseline in the longer-duration arm compared with the shorter-duration arm (27.4% vs. 21.5%, respectively).
A limitation of this study is that end-of-treatment nasal swabs were obtained in only slightly more than one-half (53%) of patients.
Pharmacists can educate parents about these study findings, which indicate that a 3-day course is just as effective as a 7-day course and a lower-dose course is just as beneficial as a higher-dose course of amoxicillin in treating uncomplicated CAP in children.
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