Region (countries)
|
Africa (Ghana, South Africa, Zambia) Asia (India, Pakistan, Vietnam) South America (Columbia, Mexico)
|
Pakistan (Asia)
|
Africa (Egypt, Ghana) Asia (Bangladesh, Vietnam)
|
Data collection dates
|
1999–2002
|
2005–2006
|
2005–2008
|
Enrollment criteria
|
3–59 months
|
3–59 months
|
3–59 months
|
Study design
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Randomized multicenter equivalency study
|
Randomized multicenter equivalency study
|
Multicenter observational study
|
Intervention arm
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Oral amoxicillin 45 mg/kg/day for 5 days
|
Oral amoxicillin 80–90 mg/kg/day for 5 days
|
-
|
Control arm (or standard of care)
|
Intravenous 200,000 IU penicillin G for 2 days then oral amoxicillin 45 mg/kg/day for 3 days (total 5 days)
|
Intravenous ampicillin 100 mg/kg/day for 2 days then oral amoxicillin for 3 days (total 5 days)
|
Amoxicillin 80–90 mg/kg/day for 5 days
|
Blinding
|
No
|
No
|
-
|
Study site type(s)
|
Pediatric department of tertiary care hospitals
|
Pediatric department of tertiary care hospitals
|
Pediatric department of tertiary care and second-level hospitals, health centers
|
Number of study sites
|
9
|
7
|
5
|
Primary outcome
|
Equivalence
|
Equivalence
|
Treatment failure
|
Treatment failure definition
|
Day of assignment
|
Day 3
|
Day 6
|
Day 6
|
Respiratory ratea
|
No
|
No
|
No
|
Fever >38 °C and LCI
|
No
|
Yes (days 3–6)
|
Yes (day 3)
|
Fever >38 °C
|
No
|
Yes (day 6)
|
Yes (day 6)
|
LCI
|
Yes (day 3)
|
Yes (day 6)
|
Yes (day 6)
|
Convulsions
|
Yes (days 1–3)
|
Yes (days 1–6)
|
Yes (days 1–6)
|
Abnormally sleepy
|
Yes (days 1–3)
|
Yes (days 1–6)
|
Yes (days 1–6)
|
Inability to drink
|
Yes (days 1–3)
|
Yes (days 1–6)
|
Yes (days 1–6)
|
Stridor in calm child
|
No
|
No
|
No
|
Malnutrition
|
No
|
No
|
No
|
Cyanosis
|
Yes (days 1–3)
|
Yes (days 1–6)
|
Yes (days 1–6)
|
SpO2
|
<80 % at sea-level or <75 % below sea-level (days 1–3)
|
No
|
No
|
Antibiotic change
|
Yes (days 1–3)
|
No
|
Yes (days 1–6)
|
Hospitalization
|
No
|
Yes, if related to pneumonia (days 1–6)
|
No
|
Serious drug reaction
|
Yes (days 1–3)
|
No
|
Yes (days 1–6)
|
Serious adverse event
|
No
|
Yes (days 1–6)
|
No
|
New comorbid condition
|
Yes (days 1–3)
|
Yes, if required antibiotic (days 1–6)
|
Yes (days 1–6)
|
Lost to follow-up
|
Yes (days 1–3)
|
Yes (days 1–6)
|
Yes (day 6)
|
Study withdrawal
|
Yes (days 1–3)
|
Yes (days 1–6)
|
No
|
Death
|
Yes (days 1–3)
|
Yes (days 1–14)
|
Yes (days 1–6)
|
Study participants and description
|
Sample sizeb
|
1702
|
2037
|
823
|
Age:
|
3–11 months
|
1045/1669 (62.6 %)
|
1311/2037 (64.4 %)
|
562/873 (64.4 %)
|
|
12–59 months
|
624/1669 (37.4 %)
|
726/2037 (35.6 %)
|
310/873 (35.5 %)
|
Treatment failure ratec
|
328/1702 (19.3 %)
|
164/2037 (8.1 %)
|
76/823 (9.2 %)
|
Independent predictors of treatment failurec OR/RR (95 % CI)
|
Age 3–11 months, 2.72 OR (95 % CI 1.95–3.79)
|
Age 3–5 months, 3.22 OR, (95 % CI 1.87–5.52)
|
Age 3–5 months, 1.96 RR (95 % CI 1.09–3.51)
|
Very fast breathing, 1.94 OR (95 % CI 1.42–2.65)d
|
Very fast breathing, 1.65 OR (95 % CI 1.07–2.57)d
|
Very fast breathing, 12.5 RR (95 % CI 1.74–89.1)d
|
SpO2 < 90 %, 2.11 OR (95 % CI 1.6–2.78)
|
Weight for age z score <−2, 1.79 OR (95 % CI 1.23–2.60)
| |