Artesunate-pyronaridine compared to artesunate plus mefloquine for treating uncomplicated P. falciparum malaria
Patient or population: Patients with uncomplicated P. falciparum malaria Settings: Malaria endemic areas Intervention: Artesunate-pyronaridine (AS-Pyr) Comparison: Artesunate plus mefloquine (AS+MQ)
Outcomes		Number of participants having adverse events (95% CI)		No of participants (trials)	Quality of the evidence (GRADE)
		AS+MQ	AS-Pyr
Serious adverse events (including deaths)		7 per 1000	0 more per 1000 (From 5 fewer to 21 more)	1271(1 trial)	low 1,2,3,4
Adverse events leading to withdrawal		9 per 1000	3 fewer per 1000 (From 7 fewer to 7 more)	1271(1 trial)	low 1,2,3,4
Gastroenterological	Vomiting	2 per 100	0 more per 100 (From 1 fewer to 2 more)	1271(1 trial)	low 1,2,5,6
	Diarrhoea	2 per 100	1 fewer per 100 (From 2 fewer to 0 more)	1271(1 trial)	low 1,2,5,6
	Abdominal pain	—	—	—	—7
Neuropsychiatric	Headache	10 per 100	2 more per 100 (From 2 fewer to 6 more)	1271(1 trial)	low 1,2,5,6
	Dizziness	7 per 100	4 fewer per 100 (From 5 fewer to 2 fewer)	1271(1 trial)	low 1,2,5,6
Cardiorespiratory	Cough	2 per 100	2 more per 100 (From 1 fewer to 4 more)	1271(1 trial)	low 1,2,5,6
	ECG abnormality	7 per 1000	0 more per 1000 (From 7 fewer to 21 more)	1271(1 trial)	low 1,2,3,8
	Prolonged QT interval	7 per 100	7 fewer per 100 (From 7 fewer to 4 more)	1271(1 trial)	moderate 1,2,3,6
Musculoskeletal/ dermatological	Myalgia	4 per 100	2 more per 100 (From 1 fewer to 5 more)	1271(1 trial)	low 1,2,5,6
Biochemical	Alanine aminotransferase Grade 3 or 4 toxicity	2 per 1000	16 more per 1000 (From 0 fewer to 110 more)	1271(1 trial)	low 1,2,3,8
	Aspartate aminotransferase Grade 3 or 4 toxicity	0 per 1000	11 more per 1000 (From 0 more to 161 more)	1271(1 trial)	low 1,2,3,8
The assumed risk of adverse events in the artesunate plus mefloquine group is the risk from the single trial. The corresponding risk with artesunate-pyronaridine (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval.
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
1 No serious risk of bias: This single trial is at low risk of bias. 2 No serious inconsistency: Not applicable as only one trial. 3 Downgraded by one for serious indirectness: This trial excluded children aged below five years. 4 Downgraded by one for imprecision: Trials of this size do not exclude the possibility of rare but clinically important adverse effects. 5 Downgraded by two for very serious indirectness: This trial excluded children aged less than five years. 6 No serious imprecision: The finding is of no difference between treatments and the sample size is adequately powered to detect differences if they existed. 7 This outcome was not reported. 8 Downgraded by one for serious imprecision: The 95% CI is wide and includes both no difference and clinically important differences.