The efficacy and safety of a new fixed-dose combination of amodiaquine and artesunate in young African children with acute uncomplicated Plasmodium falciparum
Abstract Background Artesunate (AS) plus amodiaquine (AQ) is one artemisinin-based combination (ACT) recommended by the WHO for treating Plasmodium falciparum malaria. Fixed-dose AS/AQ is new, but its safety and efficacy are hitherto untested. Methods A randomized, open-label trial was conducted com...
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ftdoajarticles:oai:doaj.org/article:95fed554d3034e95b72ec91cfb1efad9 2023-05-15T15:18:08+02:00 The efficacy and safety of a new fixed-dose combination of amodiaquine and artesunate in young African children with acute uncomplicated Plasmodium falciparum Kiechel Jean Konaté Amadou T Ouédraogo Amidou Diarra Amidou Gansané Adama Tiono Alfred B Sirima Sodiomon B Morgan Caroline C Olliaro Piero L Taylor Walter RJ 2009-03-01T00:00:00Z https://doi.org/10.1186/1475-2875-8-48 https://doaj.org/article/95fed554d3034e95b72ec91cfb1efad9 EN eng BMC http://www.malariajournal.com/content/8/1/48 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-8-48 1475-2875 https://doaj.org/article/95fed554d3034e95b72ec91cfb1efad9 Malaria Journal, Vol 8, Iss 1, p 48 (2009) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2009 ftdoajarticles https://doi.org/10.1186/1475-2875-8-48 2022-12-31T12:32:48Z Abstract Background Artesunate (AS) plus amodiaquine (AQ) is one artemisinin-based combination (ACT) recommended by the WHO for treating Plasmodium falciparum malaria. Fixed-dose AS/AQ is new, but its safety and efficacy are hitherto untested. Methods A randomized, open-label trial was conducted comparing the efficacy (non-inferiority design) and safety of fixed (F) dose AS (25 mg)/AQ (67.5 mg) to loose (L) AS (50 mg) + AQ (153 mg) in 750, P . falciparum -infected children from Burkina Faso aged 6 months to 5 years. Dosing was by age. Primary efficacy endpoint was Day (D) 28, PCR-corrected, parasitological cure rate. Recipients of rescue treatment were counted as failures and new infections as cured. Documented, common toxicity criteria (CTC) graded adverse events (AEs) defined safety. Results Recruited and evaluable children numbered 750 (375/arm) and 682 (90.9%), respectively. There were 8 (AS/AQ) and 6 (AS+AQ) early treatment failures and one D7 failure (AS+AQ). Sixteen (AS/AQ) and 12 (AS+AQ) patients had recurrent parasitaemia (PCR new infections 10 and 6, respectively). Fourteen patients per arm required rescue treatment for vomiting/spitting out study drugs. Efficacy rates were 92.1% in both arms: AS/AQ = 315/342 (95% CI: 88.7–94.7) vs. AS+AQ = 313/340 (95% CI: 88.6–94.7). Non-inferiority was demonstrated at two-sided α = 0.05: Δ (AS+AQ – AS/AQ) = 0.0% (95% CI: -4.1% to 4.0%). D28, Kaplan Meier PCR-corrected cure rates (all randomized children) were similar: 93.7% (AS/AQ) vs. 93.2% (AS+AQ) Δ = -0.5 (95% CI -4.2 to 3.0%). By D2, both arms had rapid parasite (F & L, 97.8% aparasitaemic) and fever (97.2% [F], 96.0% [L] afebrile) clearances. Both treatments were well tolerated. Drug-induced vomiting numbered 8/375 (2.1%) and 6/375 (1.6%) in the fixed and loose arms, respectively ( p = 0.59). One patient developed asymptomatic, CTC grade 4 hepatitis (AST 1052, ALT 936). Technical difficulties precluded the assessment and risk of neutropaenia for all patients. Conclusion Fixed dose AS/AQ was efficacious and ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Meier ENVELOPE(-45.900,-45.900,-60.633,-60.633) Malaria Journal 8 1 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Kiechel Jean Konaté Amadou T Ouédraogo Amidou Diarra Amidou Gansané Adama Tiono Alfred B Sirima Sodiomon B Morgan Caroline C Olliaro Piero L Taylor Walter RJ The efficacy and safety of a new fixed-dose combination of amodiaquine and artesunate in young African children with acute uncomplicated Plasmodium falciparum |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Artesunate (AS) plus amodiaquine (AQ) is one artemisinin-based combination (ACT) recommended by the WHO for treating Plasmodium falciparum malaria. Fixed-dose AS/AQ is new, but its safety and efficacy are hitherto untested. Methods A randomized, open-label trial was conducted comparing the efficacy (non-inferiority design) and safety of fixed (F) dose AS (25 mg)/AQ (67.5 mg) to loose (L) AS (50 mg) + AQ (153 mg) in 750, P . falciparum -infected children from Burkina Faso aged 6 months to 5 years. Dosing was by age. Primary efficacy endpoint was Day (D) 28, PCR-corrected, parasitological cure rate. Recipients of rescue treatment were counted as failures and new infections as cured. Documented, common toxicity criteria (CTC) graded adverse events (AEs) defined safety. Results Recruited and evaluable children numbered 750 (375/arm) and 682 (90.9%), respectively. There were 8 (AS/AQ) and 6 (AS+AQ) early treatment failures and one D7 failure (AS+AQ). Sixteen (AS/AQ) and 12 (AS+AQ) patients had recurrent parasitaemia (PCR new infections 10 and 6, respectively). Fourteen patients per arm required rescue treatment for vomiting/spitting out study drugs. Efficacy rates were 92.1% in both arms: AS/AQ = 315/342 (95% CI: 88.7–94.7) vs. AS+AQ = 313/340 (95% CI: 88.6–94.7). Non-inferiority was demonstrated at two-sided α = 0.05: Δ (AS+AQ – AS/AQ) = 0.0% (95% CI: -4.1% to 4.0%). D28, Kaplan Meier PCR-corrected cure rates (all randomized children) were similar: 93.7% (AS/AQ) vs. 93.2% (AS+AQ) Δ = -0.5 (95% CI -4.2 to 3.0%). By D2, both arms had rapid parasite (F & L, 97.8% aparasitaemic) and fever (97.2% [F], 96.0% [L] afebrile) clearances. Both treatments were well tolerated. Drug-induced vomiting numbered 8/375 (2.1%) and 6/375 (1.6%) in the fixed and loose arms, respectively ( p = 0.59). One patient developed asymptomatic, CTC grade 4 hepatitis (AST 1052, ALT 936). Technical difficulties precluded the assessment and risk of neutropaenia for all patients. Conclusion Fixed dose AS/AQ was efficacious and ... |
format |
Article in Journal/Newspaper |
author |
Kiechel Jean Konaté Amadou T Ouédraogo Amidou Diarra Amidou Gansané Adama Tiono Alfred B Sirima Sodiomon B Morgan Caroline C Olliaro Piero L Taylor Walter RJ |
author_facet |
Kiechel Jean Konaté Amadou T Ouédraogo Amidou Diarra Amidou Gansané Adama Tiono Alfred B Sirima Sodiomon B Morgan Caroline C Olliaro Piero L Taylor Walter RJ |
author_sort |
Kiechel Jean |
title |
The efficacy and safety of a new fixed-dose combination of amodiaquine and artesunate in young African children with acute uncomplicated Plasmodium falciparum |
title_short |
The efficacy and safety of a new fixed-dose combination of amodiaquine and artesunate in young African children with acute uncomplicated Plasmodium falciparum |
title_full |
The efficacy and safety of a new fixed-dose combination of amodiaquine and artesunate in young African children with acute uncomplicated Plasmodium falciparum |
title_fullStr |
The efficacy and safety of a new fixed-dose combination of amodiaquine and artesunate in young African children with acute uncomplicated Plasmodium falciparum |
title_full_unstemmed |
The efficacy and safety of a new fixed-dose combination of amodiaquine and artesunate in young African children with acute uncomplicated Plasmodium falciparum |
title_sort |
efficacy and safety of a new fixed-dose combination of amodiaquine and artesunate in young african children with acute uncomplicated plasmodium falciparum |
publisher |
BMC |
publishDate |
2009 |
url |
https://doi.org/10.1186/1475-2875-8-48 https://doaj.org/article/95fed554d3034e95b72ec91cfb1efad9 |
long_lat |
ENVELOPE(-45.900,-45.900,-60.633,-60.633) |
geographic |
Arctic Meier |
geographic_facet |
Arctic Meier |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 8, Iss 1, p 48 (2009) |
op_relation |
http://www.malariajournal.com/content/8/1/48 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-8-48 1475-2875 https://doaj.org/article/95fed554d3034e95b72ec91cfb1efad9 |
op_doi |
https://doi.org/10.1186/1475-2875-8-48 |
container_title |
Malaria Journal |
container_volume |
8 |
container_issue |
1 |
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1766348357848006656 |