TY - JOUR
T1 - Analysis of serious adverse events in a paediatric fast breathing pneumonia clinical trial in Malawi
AU - Nkwopara, Evangelyn
AU - Schmicker, Robert
AU - Mvalo, Tisungane
AU - Phiri, Melda
AU - Phiri, Ajib
AU - Couasnon, Mari
AU - McCollum, Eric D.
AU - Ginsburg, Amy Sarah
N1 - Funding Information:
Funding This research is supported by a grant from the Bill and Melinda Gates Foundation.
Funding Information:
This research is supported by a grant from the Bill and Melinda Gates Foundation. We thank the dedicated study staff at the University of North Carolina (UNC) Project, Lilongwe Medical Relief Fund Trust for providing patient care and data collection; the UNC Project Lilongwe community advisory board for their work as participant advocates and their assistance with community outreach; Triclinium Clinical Development for facilitating data review and management; and the Malawi Ministry of Health. We also thank the trial participants, their caregivers and the local community in Lilongwe, Malawi for their participation and support.
Publisher Copyright:
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - 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.
AB - 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.
KW - pneumonia
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UR - http://www.scopus.com/inward/citedby.url?scp=85072035972&partnerID=8YFLogxK
U2 - 10.1136/bmjresp-2019-000415
DO - 10.1136/bmjresp-2019-000415
M3 - Article
C2 - 31548894
AN - SCOPUS:85072035972
SN - 2052-4439
VL - 6
JO - BMJ Open Respiratory Research
JF - BMJ Open Respiratory Research
IS - 1
M1 - e00415
ER -