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Amoxicillin for 3 or 5 Days for Chest-Indrawing Pneumonia in Malawian Children.
N Engl J Med. 2020 07 02; 383(1):13-23.NEJM

Abstract

BACKGROUND

Evidence regarding the appropriate duration of treatment with antibiotic agents in children with pneumonia in low-resource settings in Africa is lacking.

METHODS

We conducted a double-blind, randomized, controlled, noninferiority trial in Lilongwe, Malawi, to determine whether treatment with amoxicillin for 3 days is less effective than treatment for 5 days in children with chest-indrawing pneumonia (cough lasting <14 days or difficulty breathing, along with visible indrawing of the chest wall with or without fast breathing for age). Children not infected with human immunodeficiency virus (HIV) who were 2 to 59 months of age and had chest-indrawing pneumonia were randomly assigned to receive amoxicillin twice daily for either 3 days or 5 days. Children were followed for 14 days. The primary outcome was treatment failure by day 6; noninferiority of the 3-day regimen to the 5-day regimen would be shown if the percentage of children with treatment failure in the 3-day group was no more than 1.5 times that in the 5-day group. Prespecified secondary analyses included assessment of treatment failure or relapse by day 14.

RESULTS

From March 29, 2016, to April 1, 2019, a total of 3000 children underwent randomization: 1497 children were assigned to the 3-day group, and 1503 to the 5-day group. Among children with day 6 data available, treatment failure had occurred in 5.9% in the 3-day group (85 of 1442 children) and in 5.2% (75 of 1456) in the 5-day group (adjusted difference, 0.7 percentage points; 95% confidence interval [CI], -0.9 to 2.4) - a result that satisfied the criterion for noninferiority of the 3-day regimen to the 5-day regimen. Among children with day 14 data available, 176 of 1411 children (12.5%) in the 3-day group and 154 of 1429 (10.8%) in the 5-day group had had treatment failure by day 6 or relapse by day 14 (between-group difference, 1.7 percentage points; 95% CI, -0.7 to 4.1). The percentage of children with serious adverse events was similar in the two groups (9.8% in the 3-day group and 8.8% in the 5-day group).

CONCLUSIONS

In HIV-uninfected Malawian children, treatment with amoxicillin for chest-indrawing pneumonia for 3 days was noninferior to treatment for 5 days. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT02678195.).

Authors+Show Affiliations

From the Department of Biostatistics, University of Washington Clinical Trial Center, Seattle (A.-S.G., R.S., J.H., S.M.); the University of North Carolina Project, Lilongwe Medical Relief Fund Trust, Tidziwe Centre (T.M., M.P., C.B.N.), and Acute Respiratory Infection and Emergency Triage Assessment and Treatment, Malawi Ministry of Health (N.L.), Lilongwe, and the Department of Pediatrics and Child Health, College of Medicine, University of Malawi, Blantyre (A.P.) - all in Malawi; Save the Children, Fairfield, CT (E.N.); and Eudowood Division of Pediatric Respiratory Sciences, Department of Pediatrics, Johns Hopkins School of Medicine and Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore (E.D.M.).From the Department of Biostatistics, University of Washington Clinical Trial Center, Seattle (A.-S.G., R.S., J.H., S.M.); the University of North Carolina Project, Lilongwe Medical Relief Fund Trust, Tidziwe Centre (T.M., M.P., C.B.N.), and Acute Respiratory Infection and Emergency Triage Assessment and Treatment, Malawi Ministry of Health (N.L.), Lilongwe, and the Department of Pediatrics and Child Health, College of Medicine, University of Malawi, Blantyre (A.P.) - all in Malawi; Save the Children, Fairfield, CT (E.N.); and Eudowood Division of Pediatric Respiratory Sciences, Department of Pediatrics, Johns Hopkins School of Medicine and Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore (E.D.M.).From the Department of Biostatistics, University of Washington Clinical Trial Center, Seattle (A.-S.G., R.S., J.H., S.M.); the University of North Carolina Project, Lilongwe Medical Relief Fund Trust, Tidziwe Centre (T.M., M.P., C.B.N.), and Acute Respiratory Infection and Emergency Triage Assessment and Treatment, Malawi Ministry of Health (N.L.), Lilongwe, and the Department of Pediatrics and Child Health, College of Medicine, University of Malawi, Blantyre (A.P.) - all in Malawi; Save the Children, Fairfield, CT (E.N.); and Eudowood Division of Pediatric Respiratory Sciences, Department of Pediatrics, Johns Hopkins School of Medicine and Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore (E.D.M.).From the Department of Biostatistics, University of Washington Clinical Trial Center, Seattle (A.-S.G., R.S., J.H., S.M.); the University of North Carolina Project, Lilongwe Medical Relief Fund Trust, Tidziwe Centre (T.M., M.P., C.B.N.), and Acute Respiratory Infection and Emergency Triage Assessment and Treatment, Malawi Ministry of Health (N.L.), Lilongwe, and the Department of Pediatrics and Child Health, College of Medicine, University of Malawi, Blantyre (A.P.) - all in Malawi; Save the Children, Fairfield, CT (E.N.); and Eudowood Division of Pediatric Respiratory Sciences, Department of Pediatrics, Johns Hopkins School of Medicine and Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore (E.D.M.).From the Department of Biostatistics, University of Washington Clinical Trial Center, Seattle (A.-S.G., R.S., J.H., S.M.); the University of North Carolina Project, Lilongwe Medical Relief Fund Trust, Tidziwe Centre (T.M., M.P., C.B.N.), and Acute Respiratory Infection and Emergency Triage Assessment and Treatment, Malawi Ministry of Health (N.L.), Lilongwe, and the Department of Pediatrics and Child Health, College of Medicine, University of Malawi, Blantyre (A.P.) - all in Malawi; Save the Children, Fairfield, CT (E.N.); and Eudowood Division of Pediatric Respiratory Sciences, Department of Pediatrics, Johns Hopkins School of Medicine and Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore (E.D.M.).From the Department of Biostatistics, University of Washington Clinical Trial Center, Seattle (A.-S.G., R.S., J.H., S.M.); the University of North Carolina Project, Lilongwe Medical Relief Fund Trust, Tidziwe Centre (T.M., M.P., C.B.N.), and Acute Respiratory Infection and Emergency Triage Assessment and Treatment, Malawi Ministry of Health (N.L.), Lilongwe, and the Department of Pediatrics and Child Health, College of Medicine, University of Malawi, Blantyre (A.P.) - all in Malawi; Save the Children, Fairfield, CT (E.N.); and Eudowood Division of Pediatric Respiratory Sciences, Department of Pediatrics, Johns Hopkins School of Medicine and Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore (E.D.M.).From the Department of Biostatistics, University of Washington Clinical Trial Center, Seattle (A.-S.G., R.S., J.H., S.M.); the University of North Carolina Project, Lilongwe Medical Relief Fund Trust, Tidziwe Centre (T.M., M.P., C.B.N.), and Acute Respiratory Infection and Emergency Triage Assessment and Treatment, Malawi Ministry of Health (N.L.), Lilongwe, and the Department of Pediatrics and Child Health, College of Medicine, University of Malawi, Blantyre (A.P.) - all in Malawi; Save the Children, Fairfield, CT (E.N.); and Eudowood Division of Pediatric Respiratory Sciences, Department of Pediatrics, Johns Hopkins School of Medicine and Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore (E.D.M.).From the Department of Biostatistics, University of Washington Clinical Trial Center, Seattle (A.-S.G., R.S., J.H., S.M.); the University of North Carolina Project, Lilongwe Medical Relief Fund Trust, Tidziwe Centre (T.M., M.P., C.B.N.), and Acute Respiratory Infection and Emergency Triage Assessment and Treatment, Malawi Ministry of Health (N.L.), Lilongwe, and the Department of Pediatrics and Child Health, College of Medicine, University of Malawi, Blantyre (A.P.) - all in Malawi; Save the Children, Fairfield, CT (E.N.); and Eudowood Division of Pediatric Respiratory Sciences, Department of Pediatrics, Johns Hopkins School of Medicine and Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore (E.D.M.).From the Department of Biostatistics, University of Washington Clinical Trial Center, Seattle (A.-S.G., R.S., J.H., S.M.); the University of North Carolina Project, Lilongwe Medical Relief Fund Trust, Tidziwe Centre (T.M., M.P., C.B.N.), and Acute Respiratory Infection and Emergency Triage Assessment and Treatment, Malawi Ministry of Health (N.L.), Lilongwe, and the Department of Pediatrics and Child Health, College of Medicine, University of Malawi, Blantyre (A.P.) - all in Malawi; Save the Children, Fairfield, CT (E.N.); and Eudowood Division of Pediatric Respiratory Sciences, Department of Pediatrics, Johns Hopkins School of Medicine and Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore (E.D.M.).From the Department of Biostatistics, University of Washington Clinical Trial Center, Seattle (A.-S.G., R.S., J.H., S.M.); the University of North Carolina Project, Lilongwe Medical Relief Fund Trust, Tidziwe Centre (T.M., M.P., C.B.N.), and Acute Respiratory Infection and Emergency Triage Assessment and Treatment, Malawi Ministry of Health (N.L.), Lilongwe, and the Department of Pediatrics and Child Health, College of Medicine, University of Malawi, Blantyre (A.P.) - all in Malawi; Save the Children, Fairfield, CT (E.N.); and Eudowood Division of Pediatric Respiratory Sciences, Department of Pediatrics, Johns Hopkins School of Medicine and Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore (E.D.M.).From the Department of Biostatistics, University of Washington Clinical Trial Center, Seattle (A.-S.G., R.S., J.H., S.M.); the University of North Carolina Project, Lilongwe Medical Relief Fund Trust, Tidziwe Centre (T.M., M.P., C.B.N.), and Acute Respiratory Infection and Emergency Triage Assessment and Treatment, Malawi Ministry of Health (N.L.), Lilongwe, and the Department of Pediatrics and Child Health, College of Medicine, University of Malawi, Blantyre (A.P.) - all in Malawi; Save the Children, Fairfield, CT (E.N.); and Eudowood Division of Pediatric Respiratory Sciences, Department of Pediatrics, Johns Hopkins School of Medicine and Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore (E.D.M.).

Pub Type(s)

Equivalence Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32609979

Citation

Ginsburg, Amy-Sarah, et al. "Amoxicillin for 3 or 5 Days for Chest-Indrawing Pneumonia in Malawian Children." The New England Journal of Medicine, vol. 383, no. 1, 2020, pp. 13-23.
Ginsburg AS, Mvalo T, Nkwopara E, et al. Amoxicillin for 3 or 5 Days for Chest-Indrawing Pneumonia in Malawian Children. N Engl J Med. 2020;383(1):13-23.
Ginsburg, A. S., Mvalo, T., Nkwopara, E., McCollum, E. D., Phiri, M., Schmicker, R., Hwang, J., Ndamala, C. B., Phiri, A., Lufesi, N., & May, S. (2020). Amoxicillin for 3 or 5 Days for Chest-Indrawing Pneumonia in Malawian Children. The New England Journal of Medicine, 383(1), 13-23. https://doi.org/10.1056/NEJMoa1912400
Ginsburg AS, et al. Amoxicillin for 3 or 5 Days for Chest-Indrawing Pneumonia in Malawian Children. N Engl J Med. 2020 07 2;383(1):13-23. PubMed PMID: 32609979.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Amoxicillin for 3 or 5 Days for Chest-Indrawing Pneumonia in Malawian Children. AU - Ginsburg,Amy-Sarah, AU - Mvalo,Tisungane, AU - Nkwopara,Evangelyn, AU - McCollum,Eric D, AU - Phiri,Melda, AU - Schmicker,Robert, AU - Hwang,Jun, AU - Ndamala,Chifundo B, AU - Phiri,Ajib, AU - Lufesi,Norman, AU - May,Susanne, PY - 2020/7/2/entrez PY - 2020/7/2/pubmed PY - 2020/7/15/medline SP - 13 EP - 23 JF - The New England journal of medicine JO - N. Engl. J. Med. VL - 383 IS - 1 N2 - BACKGROUND: Evidence regarding the appropriate duration of treatment with antibiotic agents in children with pneumonia in low-resource settings in Africa is lacking. METHODS: We conducted a double-blind, randomized, controlled, noninferiority trial in Lilongwe, Malawi, to determine whether treatment with amoxicillin for 3 days is less effective than treatment for 5 days in children with chest-indrawing pneumonia (cough lasting <14 days or difficulty breathing, along with visible indrawing of the chest wall with or without fast breathing for age). Children not infected with human immunodeficiency virus (HIV) who were 2 to 59 months of age and had chest-indrawing pneumonia were randomly assigned to receive amoxicillin twice daily for either 3 days or 5 days. Children were followed for 14 days. The primary outcome was treatment failure by day 6; noninferiority of the 3-day regimen to the 5-day regimen would be shown if the percentage of children with treatment failure in the 3-day group was no more than 1.5 times that in the 5-day group. Prespecified secondary analyses included assessment of treatment failure or relapse by day 14. RESULTS: From March 29, 2016, to April 1, 2019, a total of 3000 children underwent randomization: 1497 children were assigned to the 3-day group, and 1503 to the 5-day group. Among children with day 6 data available, treatment failure had occurred in 5.9% in the 3-day group (85 of 1442 children) and in 5.2% (75 of 1456) in the 5-day group (adjusted difference, 0.7 percentage points; 95% confidence interval [CI], -0.9 to 2.4) - a result that satisfied the criterion for noninferiority of the 3-day regimen to the 5-day regimen. Among children with day 14 data available, 176 of 1411 children (12.5%) in the 3-day group and 154 of 1429 (10.8%) in the 5-day group had had treatment failure by day 6 or relapse by day 14 (between-group difference, 1.7 percentage points; 95% CI, -0.7 to 4.1). The percentage of children with serious adverse events was similar in the two groups (9.8% in the 3-day group and 8.8% in the 5-day group). CONCLUSIONS: In HIV-uninfected Malawian children, treatment with amoxicillin for chest-indrawing pneumonia for 3 days was noninferior to treatment for 5 days. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT02678195.). SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/32609979/Amoxicillin_for_3_or_5_Days_for_Chest-Indrawing_Pneumonia_in_Malawian_Children L2 - http://www.nejm.org/doi/full/10.1056/NEJMoa1912400?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -