Na‐Bangchang 1996

Methods	Trial design: Open‐label, randomized, controlled trial with two arms. Follow up: Physical exam at baseline. Hospitalized until day 28, blood smear every six hours until negative, then daily until day 28. Adverse event monitoring: Monitoring of adverse events was performed daily until day 7, then once weekly until day 28. Baseline date for age, parasite density (P. falciparum), and red blood cell count, among those randomized. Look similar. Adverse events reported among participants who completed the study.
Participants	Number enrolled:  60 Number available for analysis:  57 Inclusion criteria:  15 to 59 years, uncomplicated Plasmodium falciparum infection with density < 100,000/µl, willing to provide informed consent Exclusion criteria: History of mefloquine or quinine treatment over the last four weeks (confirmed by drug levels determined in blood using HPLC) Age range:  15 to 59 years, median 23 in group 1, 25 in group 2. Proportion male: 60/60 (100%) Pregnant women: Excluded
Interventions	arm 1) Azithromycin 500 mg at start, 250 mg after 24 and 48 hrs, plus artemether 300 mg once at start. arm 2) Doxycycline 100 mg every 12 hrs for five days, plus artemether 300 mg once at the start and 100 mg after 12 hours. Supervision of intake: Yes Other (symptomatic) medication: Not reported
Outcomes	Outcomes used in this review:  Total failure by day 28 Parasite and fever clearance time Adverse events
Notes	Location:  Mae Sot, Tak Province, Thailand (Thai‐Myanmar border) Date:  June to August 1995 (rainy season) Malaria endemicity:  Not reported Drug resistance: Resistance in study area reported to chloroquine, sulphadoxine‐pyrimethamine, and mefloquine. Method of determining parasite density:  Giemsa stained thick and thin smear, parasite count per 1000 red blood cells or per 200 WBC. No definition of negative smear. Drug source:  artemether: Artenam, Arenco nv, Belgium; doxycycline: Vibramycin, Pfizer; azithromycin: Zithromax, Pfizer. Source of funding: Japan Association of Tropical Medicine Other notes: None
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Unclear risk	No information
Allocation concealment?	Unclear risk	No information
Blinding? All outcomes	High risk	Not blinded for participants or investigators, not clear for microscopist.
Incomplete outcome data addressed? All outcomes	Low risk	Low loss to follow‐up, similar across arms: 30 and 30 randomized in respective groups, 27 (90%) and 30 (100%) results at day 28. Three were lost to follow‐up; reason not specified, but reportedly not related to malaria or adverse effects at the time of study departure.
Free of selective reporting?	High risk	Only males included
Free of other bias?	Unclear risk	Insufficient information