Table 1

Study terms and definitions

Fast breathing for ageRespiratory rate >50 breaths per minute for children t2 to <12 months of age, or >40 breaths per minute for children>12 months of age
Severe respiratory distressGrunting, nasal flaring, head nodding and/or chest indrawing
HypoxaemiaArterial oxyhaemoglobin saturation (SpO2) <90% in room air, as assessed non-invasively by a pulse oximeter
WHO IMCI general danger signsLethargy or unconsciousness, convulsions, vomiting everything or inability to drink or breastfeed
Severe acute malnutritionWeight for height/length <-3 SD, MUAC <11.5 cm, or peripheral oedema
Severe malariaPositive malaria rapid diagnostic test with any WHO IMCI general danger sign, stiff neck, abnormal bleeding, clinical jaundice, or haemoglobinuria
HIV exposureChildren<24 months of age with a HIV-infected mother
Serious adverse event Adverse event that:
  •  Results in death

  •  Is life threatening

  •  Requires inpatient hospitalisation or prolongation of existing hospitalisation

  •  Results in persistent or significant disability/incapacity

  •  Is a medical event, based on appropriate medical judgement, that may jeopardise 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

  •  Fast breathing for age

Exclusion criteria
  •  Severe respiratory distress

  •  Hypoxaemia

  •  Resolution of fast-breathing after bronchodilator challenge, if wheezing at screening examination

  •  WHO IMCI general danger signs

  •  Stridor when calm

  •  HIV seropositivity or HIV exposure

  •  Severe acute malnutrition

  •  Possible tuberculosis (coughing >14 days)

  •  Anaemia with haemoglobin <80 g/L

  •  Severe malaria

  •  Known allergy to penicillin or amoxicillin

  •  Receipt of an antibiotic treatment in the 48 hours prior to the study

  •  Hospitalised 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 jeopardise the child’s health

  •  Any non-pneumonia acute medical illness which requires antibiotic treatment as per local standard of care

  •  Participation in a clinical study of another investigational product within 12 weeks prior to randomisation or planning to begin participation during this study

  •  Prior participation in the study during a previous pneumonia diagnosis

Treatment failure
Any time on or before day 4
  •  Severe respiratory distress

  •  Hypoxaemia

  •  WHO IMCI danger signs

  •  Missing >2 study drug doses due to vomiting

  •  Change in antibiotics prescribed by a study clinician

  •  Hospitalisation due to pneumonia (if not initially admitted)

  •  Prolonged hospitalisation or re-admission due to pneumonia (if initially admitted)

  •  Death

On day 4 only
  •  Axillary temperature >38°C in the absence of a diagnosed co-infection with fever symptoms (eg, malaria)

Clinical relapse
Any time after day 4
  •  Recurrence of signs of pneumonia

  •  Signs of severe disease

NIH DAIDS severity grading
Grade 1Mild event
Grade 2Moderate event
Grade 3Severe event
Grade 4Potentially life-threatening event
Grade 5Death
  • DAIDS, Division of AIDS; IMCI, Integrated Management of Childhood Illness; MUAC, mid-upper arm circumference; NIH, National Institutes of Health.