Phimda 2007.

Methods	RCT Duration: 1 year, 6 months (July 2003 to January 2005) Adverse event monitoring: patient report
Participants	Adults and adolescents with acute undifferentiated fever (subsequent diagnoses included leptospirosis, scrub typhus, murine typhus, mixed infections) Number randomized: 296 (57 patients with subsequent diagnosis of scrub typhus) Inclusion criteria: age > 14 years; oral temperature ≥ 38°C for < 15 days; no obvious focus of infection Exclusion criteria: inability to take oral medications; pregnancy/breastfeeding; allergy to study drugs; concurrent infection; anti‐rickettsial drugs < 48 hours before enrolment Laboratory diagnosis: IFA (microimmunofluorescence) with specific IgM and/or IgG > 1:400; OR > 4‐fold increased titres in paired serum specimens
Interventions	Azithromycin 1 g daily for 3 days, followed by 500 mg daily for 2 days (n = 30) Doxycycline 200 mg day 0, then 100 mg 12‐hourly for 7 days (n = 27)
Outcomes	Resolution of fever within 5 days ("cure") Treatment failure, defined as persistence of fever or development of complications after 48 hours of treatment Time to defervescence* Adverse events *Temperature < 37.5°C maintained for > 2 measurements without anti‐pyretics
Notes	Country: Thailand Setting: 4 hospitals Funding: Thailand Research Fund, Ministry of Public Health, Thailand, and the Welcome Trust of Great Britain Follow‐up: 15 days
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Independent, computer‐generated, simple random allocation sequences
Allocation concealment (selection bias)	Low risk	Central randomization; sealed, opaque envelopes
Blinding (performance bias and detection bias) All outcomes	High risk	Open‐label. Outcome assessment "independent". Statistician blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	296 randomized. 43 excluded after randomization owing to prior antibiotics. 89 lost to follow‐up (uncertain diagnosis). 296 included in final analysis; of these 57 participants had confirmed scrub typhus. Missing data balanced between final diagnosis groups
Selective reporting (reporting bias)	Low risk	All prespecified outcomes adequately reported
Other bias	Low risk	No obvious other sources of bias