Table 1 Study definitions
Chest indrawing pneumonia | Cough less than 14 days or difficulty breathing AND visible indrawing of the chest wall with or without fast breathing for age |
Fast breathing pneumonia | Cough less than 14 days or difficulty breathing AND fast breathing for age |
Fast breathing for age | Respiratory rate > 50 breaths per minute (for children 2 to < 12 months of age) or > 40 breaths per minute (for children > 12 months of age) |
Very fast breathing for age | > 70 breaths per minute (for children 2 to < 12 months of age) or > 60 breaths per minute (for children > 12 months of age). |
Severe respiratory distress | Grunting, nasal flaring, and/or head nodding |
Hypoxemia | Arterial oxyhemoglobin saturation (SpO2) < 90% in room air, as assessed non-invasively by a pulse oximeter |
World Health Organization (WHO) Integrated Management of Childhood Illness (IMCI) general danger signs | Lethargy or unconsciousness, convulsions, vomiting everything, inability to drink or breastfeed |
Severe acute malnutrition | Weight for height/length < − 3 SD, mid-upper arm circumference (MUAC) < 11·5 cm, or peripheral edema |
Severe malaria | Positive malaria rapid diagnostic test (mRDT) with any WHO IMCI general danger sign, stiff neck, abnormal bleeding, clinical jaundice, or hemoglobinuria |
HIV-1 exposure | Children < 24 months of age with a HIV-infected mother |
Serious adverse event | Adverse event that: • Results in death • Is life threatening • Requires inpatient hospitalization or prolongation of existing hospitalization • Results in persistent or significant disability/incapacity • Is a medical event, based on appropriate medical judgment, that may jeopardize the health of the participating child or require medical or surgical intervention to prevent one of the outcomes listed |
Eligibility criteria | |
Inclusion criteria | • 2–59 months of age • Cough < 14 days or difficulty breathing • Visible indrawing of the chest wall with or without fast breathing for age • Ability and willingness of child’s caregiver to provide informed consent and to be available for follow-up for the planned duration of the study, including accepting a home visit if he/she fails to return for a scheduled study follow-up visit |
Exclusion criteria | • Severe respiratory distress • Hypoxemia • Resolution of chest indrawing after bronchodilator challenge, if wheezing at screening examination • WHO IMCI general danger signs • Stridor when calm • HIV-1 seropositivity or HIV-1 exposure • Severe acute malnutrition • Possible tuberculosis (coughing for more than 14 days) • Hemoglobin < 8·0 g/dL • Severe malaria • Known allergy to penicillin or amoxicillin • Receipt of an antibiotic treatment in the 48 h prior to the study • Hospitalized within 14 days prior to the study • Living outside the study area • Any medical or psychosocial condition or circumstance that, in the opinion of the investigators, would interfere with the conduct of the study or for which study participation might jeopardize the child’s health • Any non-pneumonia acute medical illness which requires antibiotic treatment per local standard of care • Participation in a clinical study of another investigational product within 12 weeks prior to randomization or planning to begin participation during this study • Prior participation in the study during a previous pneumonia diagnosis |
Treatment failure criteria | |
Anytime on or before day 6 | • Severe respiratory distress • Hypoxemia • WHO IMCI danger signs • Missing > 3 study drug doses due to vomiting • Change in antibiotics prescribed by a study clinician • Prolonged hospitalization or re-admission due to pneumonia • Death |
At or after initial hospitalization discharge (between 42 and 60 h post-enrollment) | • Axillary temperature > 38 °C with chest indrawing |
On day 6 | • Axillary temperature > 38 °C • Chest indrawing |