Fixed dose artesunate amodiaquine – a phase IIb, randomized comparative trial with non-fixed artesunate amodiaquine

Ogutu, Bernhards; Juma, Elizabeth; Obonyo, Charles; Jullien, Vincent; Carn, Gwénaëlle; Vaillant, Michel; Taylor, Walter; Kiechel, Jean-René

doi:10.1186/1475-2875-13-498

Cited by 10 publications

(11 citation statements)

References 58 publications

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“…Appetite increase was reported, at 40%, in our study compared to 33% for Nauclea pobiguinii and drowsiness was observed, also at 20%, for CoBaT-Y017 compared to 7% for Nauclea pobiguinii [14]. Moreover, the increased appetite would be favorable to fight anorexia, one of the symptoms of uncomplicated malaria [17]. There were neither life-threatening adverse events reported in this trial nor clinically significant adverse findings on vital signs, significant modification of biochemical, or haematological parameters attributable to CoBaT-Y017 .…”

Section: Discussionmentioning

confidence: 54%

Short-Term Safety and Tolerability of an Antimalarial Herbal Medicine, CoBaT-Y017 in Healthy Volunteers

Noudjiegbe

Gnimassou

Gbenoudon

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Background. Malaria is the most prevalent parasitic disease in Benin and the main cause of morbidity and mortality. To fight this disease, a large proportion of the population resorts to herbal drugs. However, for most of these herbal preparations, no scientific evidence of their safety or efficacy has yet been established. The aim of this study was to evaluate the short-term safety and tolerability of CoBaT-Y017 and collect some data on its antimalarial efficacy. Material and Methods. CoBaT-Y017 was formulated into syrup accommodated in 70 mL bottles. The trial involved a sample of 10 male volunteers, selected using the Lot Quality Assurance Sampling (LQAS) method and declared apparently healthy by a physician through clinical examination. During the baseline analysis, two cases of parasitaemia were detected. The volunteers were hospitalized for 5 days and orally given 35 mL of CoBaT-Y017 diluted in 1.5 L of mineral water, for four consecutive days. Safety and tolerability were monitored clinically, haematologically, biochemically, and parasitologically on days 0 to 5, 7, and 14. Adverse events were recorded by self-reporting or by a physician through clinical examinations and biological investigations. Results. 60% of the volunteers experienced no adverse events; appetite increase (40%) and drowsiness (20%) were adverse events noted. There were no changes in physical characteristics or vital signs and haematological and biochemical parameters. The two initial positive cases of parasitaemia became negative 24 hours after administration. Conclusion. CoBaT-Y017 presented a significant safety and tolerability in healthy volunteers to allow its further development by starting a phase II clinical study.

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Section: Discussionmentioning

confidence: 54%

Short-Term Safety and Tolerability of an Antimalarial Herbal Medicine, CoBaT-Y017 in Healthy Volunteers

Noudjiegbe

Gnimassou

Gbenoudon

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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“…Bazett’s and Fridericia’s were both reported in 10% ( n = 12) of trials. Five trials [ 18 , 31 , 37 – 39 ] used alternative formulae, including Wernicke et al’s [ 40 ], Hodges’ and Karen [ 41 ].…”

Section: Resultsmentioning

confidence: 99%

The arrhythmogenic cardiotoxicity of the quinoline and structurally related antimalarial drugs: a systematic review

Haeusler

Chan

Guérin

et al. 2018

BMC Med

128

111

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BackgroundSeveral quinoline and structurally related antimalarial drugs are associated with cardiovascular side effects, particularly hypotension and electrocardiographic QT interval prolongation. A prolonged QT interval is a sensitive but not specific risk marker for the development of Torsade de Pointes—a potentially lethal polymorphic ventricular tachyarrhythmia. The increasing use of quinoline and structurally related antimalarials in mass treatments to eliminate malaria rapidly highlights the need to review their cardiovascular safety profiles.MethodsThe primary objective of this systematic review was to describe the documented clinical and electrocardiographic cardiovascular side effects of quinine, mefloquine, lumefantrine, piperaquine, halofantrine, chloroquine, sulfadoxine-pyrimethamine, amodiaquine, and primaquine. Trials in healthy subjects or patients with Plasmodium falciparum or P. vivax infection were included if at least two ECGs were conducted during the trial. All trial designs were included except case reports and pooled analyses. Secondary outcomes were the methods adopted by trials for measuring and reporting the QT interval.ResultsData from trials published between 1982 and July 2016 were included. A total of 177 trials met the inclusion criteria. 35,448 participants received quinoline antimalarials in these trials, of which 18,436 participants underwent ECG evaluation. Subjects with co-medication use or comorbidities including cardiovascular disease were excluded from the majority of trials. Dihydroartemisinin-piperaquine was the drug most studied (5083 participants). Despite enormous use over the past 60 years, only 1076, 452, and 150 patients had ECG recordings reported in studies of chloroquine, amodiaquine, and primaquine respectively. Transiently high concentrations of quinine, quinidine, and chloroquine following parenteral administration have all been associated with hypotension, but there were no documented reports of death or syncope attributable to a cardiovascular cause, nor of electrocardiographic recordings of ventricular arrhythmia in these trials. The large volume of missing outcome information and the heterogeneity of ECG interval reporting and measurement methodology did not allow pooled quantitative analysis of QT interval changes.ConclusionsNo serious cardiac adverse effects were recorded in malaria clinical trials of 35,548 participants who received quinoline and structurally related antimalarials with close follow-up including 18,436 individuals who underwent ECG evaluation. While these findings provide further evidence of the rarity of serious cardiovascular events after treatment with these drugs, they also underscore the need for continued strengthening of pharmacovigilance systems for robust detection of rare drug adverse events in real-world populations. A standardised approach to measurement and reporting of ECG data in malaria trials is also needed.Trial registrationPROSPERO CRD42016036678Electronic supplementary materialThe online version of this article (10.118...

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“…Our meta-analysis further confirms established relationships between the QT interval and the demographic factors of age and sex are relevant in malaria. The QT interval does not exhibit a sex difference in childhood [10] until around puberty, when it shortens in males but not females [28], then lengthens gradually in adulthood in males more than females [11]. This difference is thought to result from pubertal changes in sex hormone levels, although the underlying mechanisms are not fully understood [11].…”

Section: Discussionmentioning

confidence: 99%

Factors affecting the electrocardiographic QT interval in malaria: A systematic review and meta-analysis of individual patient data

et al. 2020

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Fixed dose artesunate amodiaquine – a phase IIb, randomized comparative trial with non-fixed artesunate amodiaquine

Cited by 10 publications

References 58 publications

Short-Term Safety and Tolerability of an Antimalarial Herbal Medicine, CoBaT-Y017 in Healthy Volunteers

Short-Term Safety and Tolerability of an Antimalarial Herbal Medicine, CoBaT-Y017 in Healthy Volunteers

The arrhythmogenic cardiotoxicity of the quinoline and structurally related antimalarial drugs: a systematic review

Factors affecting the electrocardiographic QT interval in malaria: A systematic review and meta-analysis of individual patient data

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