Equivalency Of Oral Amoxicillin Vs Injectable Penicillin In Children With Severe Pneumonia
Information source: Boston Medical Center
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pneumonia
Intervention: Oral amoxicillin (Drug)
Sponsored by: Boston Medical Center
Official(s) and/or principal investigator(s):
Shamim Qazi, MD, Study Chair, Affiliation: World Health Organization
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.
Official title: A Randomized Multicentre Equivalency Study Of Oral Amoxicillin Versus Injectable Penicillin In Children Aged 3 To 59 Months With Severe Pneumonia
Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Primary outcome: The primary outcome was treatment failure at 48 hours.
Secondary outcome: Secondary outcomes were treatment failure at five days and 14 days.
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
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).
Minimum age: 2 Months.
Maximum age: 59 Months.
- Children aged three to 59 months admitted with severe pneumonia. Severe pneumonia is
defined as lower chest indrawing in children with cough and/or difficult breathing,
who are able to drink and do not have central cyanosis, regardless of the respiratory
rate. Known HIV infected patients in clinical category N or A (CDC) will be included.
- Presence of any danger sign during current illness (convulsions, abnormally sleepy or
difficult to awake, stridor in a calm child).
- Severe malnutrition defined as weight for age equal or less than -3 SD or
- Hospitalization in the last two weeks. This will exclude cases with possible
nosocomial pneumonia that could require second line antibiotics.
- Known prior episodes of asthma. These patients may have respiratory distress without
infection and most often do not need antibiotics. Children having had 3 or more
episodes of wheezing in the past will also be excluded. Wheezing that improves after
receiving bronchodilator therapy, as explained in the footnote . These children may
- Measles in the last month. These patients may have immune suppression.
- Previous history of HIV infection in clinical category B or C (CDC). These patients
have immune suppression and infections that may require other diagnostic or treatment
measures (see annex 1, page 39).
- Known or clinically recognizable chronic conditions (congenital cardiac or respiratory
anomalies, chronic lung disease including bronchopulmonary dysplasia, neurological
impairment that affects respiratory function, renal diseases, malignant or
- Other diseases requiring antibiotic therapy on presenting, such as meningitis, evident
tuberculosis, dysentery, osteomyelitis, septic arthritis, etc. Use of other
antibiotics needed for treatment.
- Children Lower Chest Indrawing due to non-infective cause such cardiac failure, active
rickets, or severe anemia, or with signs of severe dehydration according to WHO
criteria (see annex 2, page 42).
- Children with SaO2 <80% in room air at sea level, or SaO2 < 75% in Bogota and Mexico
(for measurement of oxygen saturation see Study Manual).
- Known prior anaphylactic reaction to penicillin or amoxycillin.
- Known antibiotic therapy for 48 hours or more prior to admission. Clinically, these
children would be considered for a change of treatment to second line antibiotics on
admission. Evidence of antibiotic use include any of the following: a) parental report
that an antibiotics has been given; b) parent can provide evidence for prescription
for antibiotics or c) has the container with antibiotic or d) recognizes medication
when shown appropriate containers for locally available antibiotics. Children that
have received antibiotics for less than 48 hours prior to admission will be accepted
in the trial.
- Inability to receive oral medications (three or more episodes of vomiting per hour).
These children should not be given oral antibiotics.
- Previous inclusion in the trial or children already included in another trial.
- Living outside the catchment area of the hospital. These patients may be difficult to
follow after discharge.
- Parental or caretaker refusal to participate in the trial.
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Ending date: January 2000
Last updated: May 2, 2006