Krudsood 2002

Methods	Trial design: A sequential, open‐label trial. Follow up: Participants were hospitalised for 28 days or agreed to come for follow‐up weekly and stay in non‐endemic malaria area. Medical history, physical exam at baseline. Clinical signs and symptoms daily until day seven, and afterwards weekly. The oral temperature, pulse and respiratory rate were obtained every four hours. Blood pressure was measured once daily. Twelve‐hourly blood smears until negative, then once daily for 28 days in hospitalised participants or weekly after discharge. Adverse event monitoring: All participants were admitted for 28 days in order to observe adverse events; daily examinations for the first seven days and weekly thereafter. Routine haematology and biochemistry at baseline, repeated weekly until day 28. Number of participants assessed for adverse events not explicit.
Participants	Number enrolled: 170 Number available for analysis: 134 Inclusion criteria:  At least 15 years, body weight at least 40 kg, asexual forms of Plasmodium falciparum in blood smear, informed consent. Exclusion criteria: Signs of severe or complicated malaria (WHO criteria 2000); inability to tolerate oral medications; pregnant or lactating; allergy or sensitivity to drugs; consumption of any antimalarial drug therapy within two weeks prior to admission. Age range: 15 to 72 years; mean (SD) 27.0 (11.9) in arm 1, 25.2 years (11.1) in arm 2   Proportion male: 122/170 (71.8%) Pregnant women: Excluded
Interventions	arm 1) Azithromycin 500 mg plus dihydroartemisinin 80 mg once a day for three days. arm 2) Dihydroartemisinin 80 mg once a day for three days plus mefloquine 10 mg/kg on the first two days and 5 mg/kg on last day. Supervision of intake: Yes Other (symptomatic) medication: not reported
Outcomes	Outcomes:  Total failure by day 28 (primary endpoint) (not used) Parasite and fever clearance time (primary endpoint) (not used) Adverse events (used)
Notes	Location:  Bangkok Hospital for Tropical Diseases, Bangkok, Thailand Date:  Not reported Malaria endemicity:  No transmission in Bangkok Drug resistance: Not reported Method of determining parasite density:  Giemsa stained thin and thick blood smears, count of asexual parasites per 200 WBCs in thick film or against 1000 red blood cells in thin films. Negative if no parasites in 200 high power fields in thick film. Baseline data: Gender, age, duration of fever, first attack, P. falciparum density, hepatomegaly, splenomegaly, laboratory data (haemoglobin, WBC counts, kidney and liver functions) reported by treatment for those randomized. Look similar. Drug source:  dihydroartemisinin: Cotexin, Beijing Cotec New Technology Corp. Beijing Wan Hui pharmaceutical group, China, 20 mg/tablet. Mefloquine: not reported Source of funding:  Mahidol University Research Grant Other notes: Study included for adverse events, but not for efficacy analysis
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	High risk	Sequential assignment to one of two regimens
Allocation concealment?	High risk	Sequential assignment to one of two regimens
Blinding? All outcomes	High risk	Open‐label study
Incomplete outcome data addressed? All outcomes	High risk	Moderate loss to follow‐up, similar across arms: 82 and 88 enrolled in respective arms, 66 (80.5%) and 68 (77.3%) results at day 28 respectively. All persons lost were blood smear negative at discharge from the hospital.
Free of selective reporting?	High risk	Adverse events not reported by treatment arm
Free of other bias?	Unclear risk	Insufficient information; no date for study reported