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The efficacy and safety of a new fixed-dose combination of amodiaquine and artesunate in young African children with acute uncomplicated Plasmodium falciparum.

Sirima SB, Tiono AB, Gansané A, Diarra A, Ouédraogo A, Konaté AT, Kiechel JR, Morgan CC, Olliaro PL, Taylor WR - Malar. J. (2009)

Bottom Line: Fixed-dose AS/AQ is new, but its safety and efficacy are hitherto untested.Documented, common toxicity criteria (CTC) graded adverse events (AEs) defined safety.Fixed dose AS/AQ was efficacious and well tolerated.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre National de Recherche et de Formation sur le Paludisme (CNRFP), BP 2208, Ouagadougou, Burkina Faso. s.sirima.cnlp@fasonet.bf

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 alpha = 0.05: Delta (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) Delta = -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 well tolerated. These data support the use of this new fixed dose combination for treating P. falciparum malaria with continued safety monitoring.

Trial registration: Current Controlled Trials ISRCTN07576538.

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Related in: MedlinePlus

Patient disposition. 1. SAE: 8 month old girl hospitalized for gastroenteritis. 2. Other reasons were: parent's/guardian's decision; patients taking anti-malarial drugs during follow up.
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Figure 1: Patient disposition. 1. SAE: 8 month old girl hospitalized for gastroenteritis. 2. Other reasons were: parent's/guardian's decision; patients taking anti-malarial drugs during follow up.

Mentions: A total of 750 patients were enrolled and randomized in the study, 375 per arm. Of these, 626 patients (83.5%) completed the study to D28. A total of 65 patients treated with AS/AQ and 59 patients treated with AS+AQ withdrew or were withdrawn from the study) (Figure 1).


The efficacy and safety of a new fixed-dose combination of amodiaquine and artesunate in young African children with acute uncomplicated Plasmodium falciparum.

Sirima SB, Tiono AB, Gansané A, Diarra A, Ouédraogo A, Konaté AT, Kiechel JR, Morgan CC, Olliaro PL, Taylor WR - Malar. J. (2009)

Patient disposition. 1. SAE: 8 month old girl hospitalized for gastroenteritis. 2. Other reasons were: parent's/guardian's decision; patients taking anti-malarial drugs during follow up.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2662869&req=5

Figure 1: Patient disposition. 1. SAE: 8 month old girl hospitalized for gastroenteritis. 2. Other reasons were: parent's/guardian's decision; patients taking anti-malarial drugs during follow up.
Mentions: A total of 750 patients were enrolled and randomized in the study, 375 per arm. Of these, 626 patients (83.5%) completed the study to D28. A total of 65 patients treated with AS/AQ and 59 patients treated with AS+AQ withdrew or were withdrawn from the study) (Figure 1).

Bottom Line: Fixed-dose AS/AQ is new, but its safety and efficacy are hitherto untested.Documented, common toxicity criteria (CTC) graded adverse events (AEs) defined safety.Fixed dose AS/AQ was efficacious and well tolerated.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre National de Recherche et de Formation sur le Paludisme (CNRFP), BP 2208, Ouagadougou, Burkina Faso. s.sirima.cnlp@fasonet.bf

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 alpha = 0.05: Delta (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) Delta = -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 well tolerated. These data support the use of this new fixed dose combination for treating P. falciparum malaria with continued safety monitoring.

Trial registration: Current Controlled Trials ISRCTN07576538.

Show MeSH
Related in: MedlinePlus