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

Sirima, Sodiomon B.; Tiono, Alfred B.; Gansané, Adama; Diarra, Amidou; Ouédraogo, Amidou; Konaté, Amadou; Kiechel, J. R.; Morgan, Caroline; Olliaro, Piero; Taylor, Walter

doi:10.1186/1475-2875-8-48

Cited by 57 publications

(64 citation statements)

References 31 publications

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“…Together with its efficacy against multidrug-resistant P. falciparum , its ability to reduce gametocyte carriage and to help reduce transmission of resistant alleles makes ACT an essential tool in malaria control and the fight to eliminate the disease [6]. The efficacy of ASAQ given as a FDC is supported by findings of clinical studies performed in locations throughout sub-Saharan Africa [12,13]. …”

Section: Discussionmentioning

confidence: 99%

Repeated treatment of recurrent uncomplicated Plasmodium falciparum malaria in Senegal with fixed-dose artesunate plus amodiaquine versus fixed-dose artemether plus lumefantrine: a randomized, open-label trial

Ndiaye

Faye

Gueye

et al. 2011

Malar J

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BackgroundThe use of artemisinin-based combination therapy (ACT) is currently recommended for treating uncomplicated malaria. The objective was to assess the efficacy and safety of repeated administrations of two fixed-dose presentations of ACT - artesunate plus amodiaquine (ASAQ) and artemether-lumefantrine (AL) - in subsequent episodes of Plasmodium falciparum malaria.MethodsA randomized comparative study was conducted in a rural community of central Senegal from August 2007 to January 2009. Children and adults with uncomplicated P. falciparum malaria were randomized to receive open-label ASAQ once daily or AL twice daily for three days. Drug doses were given according to body weight. Treatments for first episodes were supervised. For subsequent episodes, only the first intake of study drug was supervised. ECGs and audiograms were performed in patients ≥12 years of age. Primary outcome was adequate clinical and parasitological response rate (ACPR) after polymerase chain reaction (PCR) correction on day 28 for the first episode.ResultsA total of 366 patients were enrolled in the two groups (ASAQ 184, AL 182) and followed up during two malaria transmission seasons. In the intent-to-treat population, PCR-corrected ACPRs at day 28 for the first episode were 98.4% and 96.2%, respectively, in the ASAQ and AL groups. For the per-protocol population (ASAQ 183, AL 182), PCR-corrected ACPRs at day 28 for the first episode were 98.9% and 96.7%, respectively. A 100% ACPR rate was obtained at day 28 in the 60 and four patients, respectively, who experienced second and third episodes. Treatment-related adverse events were reported in 11.7% of the patients, without significant differences between the two groups. A better improvement of haemoglobin at day 28 was noted in the ASAQ versus the AL group (12.2 versus 11.8 g/dL; p = 0.03). No sign of ototoxicity was demonstrated. A prolongation of the QTc interval was observed in both groups during treatment with no clinical consequence.ConclusionsStudy results confirmed the satisfactory efficacy and safety profile of ASAQ and AL. Moreover, in patients who were treated at least twice, repeated administration of ASAQ or AL did not identify any major safety issues.Trial registrationClinicalTrials.gov identifier NCT00540410.

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Section: Discussionmentioning

confidence: 99%

Repeated treatment of recurrent uncomplicated Plasmodium falciparum malaria in Senegal with fixed-dose artesunate plus amodiaquine versus fixed-dose artemether plus lumefantrine: a randomized, open-label trial

Ndiaye

Faye

Gueye

et al. 2011

Malar J

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“…Intensity was graded nought to four (absent, mild, moderate, severe, very severe) - this analysis was only possible in the sub-group of patients from the sites who graded signs and symptoms; in two other studies [7,9] grades were recorded during the follow-up but not at enrolment, therefore TEAEs could not be analysed.…”

Section: Methodsmentioning

confidence: 99%

Clinical tolerability of artesunate-amodiaquine versus comparator treatments for uncomplicated falciparum malaria: an individual-patient analysis of eight randomized controlled trials in sub-Saharan Africa

Zwang

Dorsey

Djimdé

et al. 2012

Malar J

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BackgroundThe widespread use of artesunate-amodiaquine (ASAQ) for treating uncomplicated malaria makes it important to gather and analyse information on its tolerability.MethodsAn individual-patient tolerability analysis was conducted using data from eight randomized controlled clinical trials conducted at 17 sites in nine sub-Saharan countries comparing ASAQ to other anti-malarial treatments. All patients who received at least one dose of the study drug were included in the analysis. Differences in adverse event (AE) and treatment emergent adverse event (TEAE) were analysed by Day 28.ResultsOf the 6,179 patients enrolled (74% <5 years of age), 50% (n = 3,113) received ASAQ, 20% (n = 1,217) another ACT, and 30% (n = 1,849) a non-ACT (combination or single-agent) treatment. Overall, 8,542 AEs were recorded. The proportion of patients experiencing at least one gastro-intestinal AE on ASAQ was 43% (and higher than that with artemether-lumefantrine and dihydroartemisinin-piperaquine at two sites), and was 23% for any other AEs (not different from other treatments). Specifically, the risk of diarrhoea, vomiting, cough and weakness was lower with artemether-lumefantrine; artemether-lumefantrine and dihydroartemisinin-piperaquine carried a higher risk of pruritus, chloroquine-SP had a higher risk of nausea. Parasitological recurrence increased the risk of occurrence of any AE. No other difference was detected. Comparing AE to TEAE in patients who had pre-treatment occurrence and grades of intensity recorded, AEs were significantly more related to the pre-treatment prevalence of the symptom (p = 0.001, Fisher test); AEs overestimated TEAEs by a factor ranging from none to five-fold. The overall incidence of serious AEs (SAEs) with ASAQ was nine per 1,000 (29/3,113) and mortality was one per 1,000 (three deaths, none drug-related); both were similar to other treatments.ConclusionASAQ was comparatively well-tolerated. Safety information is important, and must be collected and analysed in a standardized way. TEAEs are a more objective measure of treatment-induced toxicity.

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“…Data on age, parasitemia, hematologic parameters (leukocyte total counts, neutrophil and lymphocyte counts, hemoglobin levels or hematocrit, platelet counts), treatment and treatment outcome were extracted from a database of seven RCTs conducted with 28-day follow-up at 14 sites in sub-Saharan Africa [6][7][8][9][10][11][12] ( Table 1 ). Data were censored for patients who did not complete follow-up or had recurrent P. falciparum infections.…”

Section: Methodsmentioning

confidence: 99%

Hematologic Parameters in Pediatric Uncomplicated Plasmodium falciparum Malaria in Sub-Saharan Africa

Olliaro

Djimdé²,

Dorsey³

et al. 2011

The American Society of Tropical Medicine and Hygiene

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Hematologic changes in acute and convalescent uncomplicated Plasmodium falciparum malaria have not been well studied, particularly in young children in Africa. Hematologic data were obtained for 3,044 children less than five years of age in seven randomized controlled trials at 14 sites. Using paired analysis between day 28 and baseline in patients without parasitologic failure as a proxy for malaria-induced effects, we found a statistically significant but clinically modest increase in leukocyte counts (5%) resulting from a larger increase in neutrophils (43%) than the decrease in lymphocytes counts (–16%); levels of hemoglobin and platelets decreased (–13% and –49%, respectively). Multivariate random effects analysis showed trends during follow-up (increased levels of hemoglobin, platelets and lymphocytes, and decreased levels of leukocytes and neutrophils) and identified explanatory variables. The risk of neutropenia increased with follow-up time independent of treatment outcome, and was lower with age, higher baseline parasitemia, and artemisinin combination treatment. These analyses provides information on hematologic variations caused by malaria.

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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

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.

Cited by 57 publications

References 31 publications

Repeated treatment of recurrent uncomplicated Plasmodium falciparum malaria in Senegal with fixed-dose artesunate plus amodiaquine versus fixed-dose artemether plus lumefantrine: a randomized, open-label trial

Repeated treatment of recurrent uncomplicated Plasmodium falciparum malaria in Senegal with fixed-dose artesunate plus amodiaquine versus fixed-dose artemether plus lumefantrine: a randomized, open-label trial

Clinical tolerability of artesunate-amodiaquine versus comparator treatments for uncomplicated falciparum malaria: an individual-patient analysis of eight randomized controlled trials in sub-Saharan Africa

Hematologic Parameters in Pediatric Uncomplicated Plasmodium falciparum Malaria in Sub-Saharan Africa

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