Effect of Amoxicillin Dose and Treatment Duration on the Need for Antibiotic Re-treatment in Children With Community-Acquired Pneumonia The CAP-IT Randomized Clinical Trial

Bielicki, Julia A, Stohr, Wolfgang, Barratt, Sam, Dunn, David, Naufal, Nishdha, Roland, Damian, Sturgeon, Kate, Finn, Adam, Rodriguez-Ruiz, Juan Pablo, Malhotra-Kumar, Surbhi
et al (show 9 more authors) (2021) Effect of Amoxicillin Dose and Treatment Duration on the Need for Antibiotic Re-treatment in Children With Community-Acquired Pneumonia The CAP-IT Randomized Clinical Trial. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 326 (17). pp. 1713-1724.

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<h4>Importance</h4>The optimal dose and duration of oral amoxicillin for children with community-acquired pneumonia (CAP) are unclear.<h4>Objective</h4>To determine whether lower-dose amoxicillin is noninferior to higher dose and whether 3-day treatment is noninferior to 7 days.<h4>Design, setting, and participants</h4>Multicenter, randomized, 2 × 2 factorial noninferiority trial enrolling 824 children, aged 6 months and older, with clinically diagnosed CAP, treated with amoxicillin on discharge from emergency departments and inpatient wards of 28 hospitals in the UK and 1 in Ireland between February 2017 and April 2019, with last trial visit on May 21, 2019.<h4>Interventions</h4>Children were randomized 1:1 to receive oral amoxicillin at a lower dose (35-50 mg/kg/d; n = 410) or higher dose (70-90 mg/kg/d; n = 404), for a shorter duration (3 days; n = 413) or a longer duration (7 days; n = 401).<h4>Main outcomes and measures</h4>The primary outcome was clinically indicated antibiotic re-treatment for respiratory infection within 28 days after randomization. The noninferiority margin was 8%. Secondary outcomes included severity/duration of 9 parent-reported CAP symptoms, 3 antibiotic-related adverse events, and phenotypic resistance in colonizing Streptococcus pneumoniae isolates.<h4>Results</h4>Of 824 participants randomized into 1 of the 4 groups, 814 received at least 1 dose of trial medication (median [IQR] age, 2.5 years [1.6-2.7]; 421 [52%] males and 393 [48%] females), and the primary outcome was available for 789 (97%). For lower vs higher dose, the primary outcome occurred in 12.6% with lower dose vs 12.4% with higher dose (difference, 0.2% [1-sided 95% CI -∞ to 4.0%]), and in 12.5% with 3-day treatment vs 12.5% with 7-day treatment (difference, 0.1% [1-sided 95% CI -∞ to 3.9]). Both groups demonstrated noninferiority with no significant interaction between dose and duration (P = .63). Of the 14 prespecified secondary end points, the only significant differences were 3-day vs 7-day treatment for cough duration (median 12 days vs 10 days; hazard ratio [HR], 1.2 [95% CI, 1.0 to 1.4]; P = .04) and sleep disturbed by cough (median, 4 days vs 4 days; HR, 1.2 [95% CI, 1.0 to 1.4]; P = .03). Among the subgroup of children with severe CAP, the primary end point occurred in 17.3% of lower-dose recipients vs 13.5% of higher-dose recipients (difference, 3.8% [1-sided 95% CI, -∞ to10%]; P value for interaction = .18) and in 16.0% with 3-day treatment vs 14.8% with 7-day treatment (difference, 1.2% [1-sided 95% CI, -∞ to 7.4%]; P value for interaction = .73).<h4>Conclusions and relevance</h4>Among children with CAP discharged from an emergency department or hospital ward (within 48 hours), lower-dose outpatient oral amoxicillin was noninferior to higher dose, and 3-day duration was noninferior to 7 days, with regard to need for antibiotic re-treatment. However, disease severity, treatment setting, prior antibiotics received, and acceptability of the noninferiority margin require consideration when interpreting the findings.<h4>Trial registration</h4>ISRCTN Identifier: ISRCTN76888927.

Item Type: Article
Uncontrolled Keywords: PERUKI, GAPRUKI, and the CAP-IT Trial Group, Humans, Community-Acquired Infections, Pneumonia, Amoxicillin, Anti-Bacterial Agents, Patient Discharge, Retreatment, Administration, Oral, Drug Administration Schedule, Severity of Illness Index, Child, Preschool, Infant, Female, Male, Duration of Therapy
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 04 Nov 2021 08:15
Last Modified: 18 Jan 2023 21:25
DOI: 10.1001/jama.2021.17843
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3142646