Ringwald 1998

Methods	Trial design: Randomized, parallel group, active controlled trial Duration of trial: 1996; duration not stated
Participants	Number randomized: 88 Age: Children in the age range five to 15 years Gender: Both Inclusion criteria: Fever at consultation or within previous 24 hrs Monoinfection with P. falciparum (parasite density = 5000 asexual parasites/µL blood) Easy access to health services Informed consent of parent or guardian Exclusion criteria: History of self-medication with antimalarials (confirmed by negative urine test) Signs and symptoms of severe or complicated malaria Severe anaemia (haemoglobin < 5.0 g/dL) Moderate or severe malnutrition
Interventions	Intervention: 1. Pyronaridine: 32 mg/kg (N = 48) (16 mg/kg on day 0, in two divided doses; 8 mg/kg on days 1 and 2) Control: 2. Chloroquine: 35 mg/kg (N = 48) (10 mg on days 0 and 1; 5 mg on day 2)
Outcomes	Outcomes used in this review: Proportions with normal serum aspartate aminotransferase (AST) enzyme levels at baseline and two-fold or greater elevations at day 7 Outcomes reported but not used in this review: Fever clearance (defined as the time from onset of treatment until Rectal temperature remained below 37.5 °C). Parasite clearance (the time required to obtain the first negative thick blood smear with subsequent blood smears remaining negative until day 14). Parasitaemia on day 14 Early treatment failure Fever clearance time Parasite clearance time Adverse events Others Haematological (Haemoglobin, counts); biochemical (mean liver functions values, creatinine, urea). In vitro drug sensitivity Gametocyte clearance
Notes	Country of recruitment: Cameroon Setting: Nlognkak Catholic missionary dispensary in Yaounde; outpatients. All interventions were supervised Source of funding: Pyronaridine provided by Institute of Parasitic Diseases, Chinese Academy of Preventive Medicine, Shanghai, China Endemicity: High; 50 to 60% chloroquine resistant Duration of follow-up: Until day 14 Comment: Proportions on whom transaminase enzyme levels were repeated on day 14 and in those in whom they were normal were not reported Trials registration: Nil
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote from report: "Patients were randomly assigned in blocks". Comment: Unpublished information provided by authors suggest that randomisation was done in "blocks of 10."
Allocation concealment (selection bias)	Low risk	Comment: Not mentioned in trial report. Quote from correspondence with authors: "central randomisation was used."
Blinding (performance bias and detection bias) Objective outcomes: parasitological and biochemical	Low risk	Comment: Not mentioned in report. Quote from correspondence: "It was blinded but the tablets were different and many patient treated with CQ suffered of pruritus". Comment: Blinding was probably compromised but risk of bias due to this may not have affected the reporting of liver enzymes that was the outcome used in this review.
Blinding (performance bias and detection bias) Subjective outcomes: adverse events	Low risk	Comment: As above. Comment: Blinding was probably compromised and risk of bias due to this may have affected the reporting or detection of some subjective adverse events, but not the objective outcome used in this review.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote from report: "Of the 88 patients enrolled in the study, 81 completed the14-day follow-up (dropout rate, 8%). Three patients in the pyronaridine group and four in the chloroquine group were lost to follow-up." Quote from correspondence: "Drop out were mainly lost to follow-up and most often after the patients were cured. We do not think that it was related to intervention." Comment: Equal numbers dropped out from each intervention arm and hence are unlikely to have differentially influenced the outcomes used in this review.
Selective reporting (reporting bias)	Low risk	Comment: The trial was not prospectively registered and the trial protocol was not available, but all outcomes stated in methods were reported.
Other bias	Unclear risk	Comment: The proportions re-tested for liver transaminases at day 14 and the proportions in whom they were normal were not reported.