Repeat assessment of examination signs among children in Malawi with fast-breathing pneumonia.

BACKGROUND: As part of a randomised controlled trial of treatment with placebo versus 3 days of amoxicillin for nonsevere fast-breathing pneumonia among Malawian children aged 2-59 months, a subset of children was hospitalised for observation. We sought to characterise the progression of fast-breathing pneumonia among children undergoing repeat assessments to better understand which children do and do not deteriorate. METHODS: Vital signs and physical examination findings, including respiratory rate, arterial oxygen saturation measured by pulse oximetry (S pO2 ), chest indrawing and temperature were assessed every 3 h for the duration of hospitalisation. Children were assessed for treatment failure during study visits on days 1, 2, 3 and 4. RESULTS: Hospital monitoring data from 436 children were included. While no children had S pO2 90-93% at baseline, 7.4% (16 of 215) of children receiving amoxicillin and 9.5% (21 of 221) receiving placebo developed S pO2 90-93% during monitoring. Similarly, no children had chest indrawing at enrolment, but 6.6% (14 of 215) in the amoxicillin group and 7.2% (16 of 221) in the placebo group went on to develop chest indrawing during hospitalisation. CONCLUSION: Repeat monitoring of children with fast-breathing pneumonia identified vital and physical examination signs not present at baseline, including S pO2 90-93% and chest indrawing. This information may support providers and policymakers in developing guidance for care of children with nonsevere pneumonia.

Analysis of serious adverse events in a paediatric fast breathing pneumonia clinical trial in Malawi.

Introduction: Pneumonia is the leading infectious killer of children. We conducted a double-blind, randomised controlled non-inferiority trial comparing placebo to amoxicillin treatment for fast breathing pneumonia in HIV-negative children aged 2-59 months in Malawi. Occurrence of serious adverse events (SAEs) during the trial were examined to assess disease progression, co-morbidities, recurrence of pneumonia and side effects of amoxicillin. Methods: Enrolled children with fast breathing for age and a history of cough <14 days or difficult breathing were randomised to either placebo or amoxicillin for 3 days, and followed for 14 days to track clinical characteristics and outcomes. Medical history, physical exam, laboratory results and any chest radiographs collected at screening, enrolment and during hospitalisation were evaluated. All SAE reports were reviewed for additional information regarding hospitalisation, course of treatment and outcome. Results: In total, 102/1126 (9.0%) enrolled children with fast breathing pneumonia were reported to have a SAE. Seventy-five per cent (n=77) of SAEs were pneumonia-related (p<0.01). Children<2 years of age represented the greatest proportion (61/77, 79.2%) of those with a pneumonia-related SAE. In the amoxicillin group, there were 46 SAEs and 5 (10.9%) cases were identified as possibly related to study drug (4 gastroenteritis and 1 fever). There were no life-threatening pneumonia SAEs or deaths in either group, and by the time of exit from the study, all children recovered without sequelae. Discussion: In this fast breathing pneumonia clinical trial, SAEs occurred infrequently in both the amoxicillin and placebo groups, and amoxicillin was well tolerated. Trial registration number: NCT02760420. https://clinicaltrials.gov/ct2/show/NCT02760420?term=ginsburg&rank=9.