PMID- 19291301
OWN - NLM
STAT- MEDLINE
DCOM- 20090505
LR  - 20220408
IS  - 1475-2875 (Electronic)
IS  - 1475-2875 (Linking)
VI  - 8
DP  - 2009 Mar 16
TI  - The efficacy and safety of a new fixed-dose combination of amodiaquine and 
      artesunate in young African children with acute uncomplicated Plasmodium 
      falciparum.
PG  - 48
LID - 10.1186/1475-2875-8-48 [doi]
AB  - 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.
FAU - Sirima, Sodiomon B
AU  - Sirima SB
AD  - Centre National de Recherche et de Formation sur le Paludisme (CNRFP), BP 2208, 
      Ouagadougou, Burkina Faso. s.sirima.cnlp@fasonet.bf
FAU - Tiono, Alfred B
AU  - Tiono AB
FAU - Gansane, Adama
AU  - Gansane A
FAU - Diarra, Amidou
AU  - Diarra A
FAU - Ouedraogo, Amidou
AU  - Ouedraogo A
FAU - Konate, Amadou T
AU  - Konate AT
FAU - Kiechel, Jean Rene
AU  - Kiechel JR
FAU - Morgan, Caroline C
AU  - Morgan CC
FAU - Olliaro, Piero L
AU  - Olliaro PL
FAU - Taylor, Walter R J
AU  - Taylor WR
LA  - eng
SI  - ISRCTN/ISRCTN07576538
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20090316
PL  - England
TA  - Malar J
JT  - Malaria journal
JID - 101139802
RN  - 0 (Antimalarials)
RN  - 0 (Artemisinins)
RN  - 0 (Drug Combinations)
RN  - 0 (amodiaquine, artesunate drug combination)
RN  - 220236ED28 (Amodiaquine)
SB  - IM
MH  - Amodiaquine/administration & dosage/adverse effects/*therapeutic use
MH  - Animals
MH  - Antimalarials/administration & dosage/adverse effects/*therapeutic use
MH  - Artemisinins/administration & dosage/adverse effects/*therapeutic use
MH  - Burkina Faso
MH  - Child, Preschool
MH  - Drug Combinations
MH  - Drug Therapy, Combination
MH  - Female
MH  - Humans
MH  - Infant
MH  - Kaplan-Meier Estimate
MH  - Malaria, Falciparum/*drug therapy
MH  - Male
MH  - Parasitemia/drug therapy
MH  - Plasmodium falciparum/*drug effects
MH  - Polymerase Chain Reaction
MH  - Treatment Outcome
PMC - PMC2662869
EDAT- 2009/03/18 09:00
MHDA- 2009/05/06 09:00
PMCR- 2009/03/16
CRDT- 2009/03/18 09:00
PHST- 2008/07/31 00:00 [received]
PHST- 2009/03/16 00:00 [accepted]
PHST- 2009/03/18 09:00 [entrez]
PHST- 2009/03/18 09:00 [pubmed]
PHST- 2009/05/06 09:00 [medline]
PHST- 2009/03/16 00:00 [pmc-release]
AID - 1475-2875-8-48 [pii]
AID - 10.1186/1475-2875-8-48 [doi]
PST - epublish
SO  - Malar J. 2009 Mar 16;8:48. doi: 10.1186/1475-2875-8-48.