Does 3-day course of oral amoxycillin benefit children of non-severe pneumonia with wheeze: a multicentric randomised controlled trial.
BACKGROUND
WHO-defined pneumonias, treated with antibiotics, are responsible for a significant proportion of childhood morbidity and mortality in the developing countries. Since substantial proportion pneumonias have a viral etiology, where children are more likely to present with wheeze, there is a concern that currently antibiotics are being over-prescribed for it. Hence the current trial was conducted with the objective to show the therapeutic equivalence of two treatments (placebo and amoxycillin) for children presenting with non-severe pneumonia with wheeze, who have persistent fast breathing after nebulisation with salbutamol, and have normal chest radiograph.


METHODS
This multi-centric, randomised placebo controlled double blind clinical trial intended to investigate equivalent efficacy of placebo and amoxicillin and was conducted in ambulatory care settings in eight government hospitals in India. Participants were children aged 2-59 months of age, who received either oral amoxycillin (31-54 mg/Kg/day, in three divided doses for three days) or placebo, and standard bronchodilator therapy. Primary outcome was clinical failure on or before day- 4.


RESULTS
We randomized 836 cases in placebo and 835 in amoxycillin group. Clinical failures occurred in 201 (24.0%) on placebo and 166 (19.9%) on amoxycillin (risk difference 4.2% in favour of antibiotic, 95% CI: 0.2 to 8.1). Adherence for both placebo and amoxycillin was >96% and 98.9% subjects were followed up on day- 4. Clinical failure was associated with (i) placebo treatment (adjusted OR = 1.28, 95% CI: 1.01 to1.62), (ii) excess respiratory rate of >10 breaths per minute (adjusted OR = 1.51, 95% CI: 1.19, 1.92), (iii) vomiting at enrolment (adjusted OR = 1.49, 95% CI: 1.13, 1.96), (iv) history of use of broncho-dilators (adjusted OR = 1.71, 95% CI: 1.30, 2.24) and (v) non-adherence (adjusted OR = 8.06, 95% CI: 4.36, 14.92).


CONCLUSIONS
Treating children with non-severe pneumonia and wheeze with a placebo is not equivalent to treatment with oral amoxycillin.


BACKGROUND
ClinicalTrials.gov NCT00407394.
Awasthi
Shally
S
King George's Medical University, Lucknow, India. sawasthi@sancharnet.in
Agarwal
Girdhar
G
Kabra
Sushil K
SK
Singhi
Sunit
S
Kulkarni
Madhuri
M
More
Vaishali
V
Niswade
Abhimanyu
A
Pillai
Raj Mohan
RM
Luke
Ravi
R
Srivastava
Neeraj M
NM
Suresh
Saradha
S
Verghese
Valsan P
VP
Raghupathy
P
P
Lodha
R
R
Walter
Stephen D
SD
D000284:Administration, Oral; D000658:Amoxicillin / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D006801:Humans; D007223:Infant; D011014:Pneumonia / Q000188:drug therapy* / Q000503:physiopathology*; D012135:Respiratory Sounds / Q000187:drug effects / Q000503:physiopathology*; D012307:Risk Factors; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D000658:Amoxicillin