Equivalency Of Oral Amoxicillin Vs Injectable Penicillin In Children With Severe Pneumonia
This is a clinical trial to determine if oral amoxicillin is equivalent in efficacy to injectable penicillin (the standard treatment) in the treatment of WHO-defined severe pneumonia in children between the ages of 2 and 59 months.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomized Multicentre Equivalency Study Of Oral Amoxicillin Versus Injectable Penicillin In Children Aged 3 To 59 Months With Severe Pneumonia|
- The primary outcome was treatment failure at 48 hours.
- Secondary outcomes were treatment failure at five days and 14 days.
|Study Start Date:||January 1998|
|Estimated Study Completion Date:||January 2000|
BACKGROUND Injectable penicillin is recommended treatment for WHO-defined severe pneumonia (lower chest indrawing [LCI]). Oral amoxicillin, if found equally effective, could reduce referral, hospitalization, and treatment costs. We aimed to determine whether oral amoxicillin and parenteral penicillin were equivalent in the treatment of severe pneumonia in children aged 3-59 months.
METHODS This multicentre randomized, open label equivalency study was conducted at tertiary care centres in 8 countries. Children aged 3-59 months with severe pneumonia were hospitalized for 48 hours and, if improved, discharged with a 5-day course of oral amoxicillin. Follow-up evaluation occurred at 5 and 14 days after enrolment. The primary outcome was treatment failure (persistence of LCI or new danger signs) at 48 hours. Analyses were by intention to treat and per protocol.
RESULTS 1702 children were randomized to receive either oral amoxicillin (857) or parenteral penicillin (845) for 48 hours. Treatment failure was 19% in each group (risk difference –0.4; 95% CI –4.2 to 3.3) at 48 hours, 22% (cumulative) in each group at 5 days, and 25% in each group at 14 days. Relapse at day 5 and 14 occurred in 45/1375 (3.4%) and 65/1330 (4.8%) of the children, respectively. Infancy (OR 2.72, 95% CI 1.95—3.79), very fast breathing (1.94, 1.42—2.65) and hypoxia (1.95, 1.34—2.82) at baseline predicted treatment failure by multivariate analysis.
CONCLUSIONS Injectable penicillin and oral amoxicillin are equivalent in the treatment of severe pneumonia in developing world areas in a controlled environment. Additional research is needed in a public health setting in rural and urban areas before these finding can be recommended for widespread implementation. Potential benefits of oral therapy for pneumonia include a decrease in the 1) the risk of needle-borne infections; 2) need for referral or hospitalization; 3) administration costs and 4) costs to the family. (word count 294).