Carbon 1995.

Methods	‐ RCT ‐ Double‐blinded ‐ Double‐dummy
Participants	‐ Number of participants enrolled: 250 ‐ Number of participants randomised: 240 ‐ Number of participants evaluated: 236 ‐ Number of dropouts: 4 (2%) ‐ Setting: 60 French General Practice clinics ‐ Age: > 15 yrs ‐ Diagnosis: rapid antigen test, throat culture ‐ Inclusion criteria: fever =/> 38 °C, odynophagia, erythema or purulent exudate of pharynx, at least one tender submaxillary lymph node, rapid antigen test positive for GABHS, followed by positive throat culture ‐ Exclusion criteria: allergy to beta‐lactams, pregnancy, lactation, chronic tonsillitis, antibiotics in 5 days preceding randomisation, no written consent
Interventions	‐ Groups: cefotiam hexetil (CTM), 200 mg twice a day for 5 days and a penicillin V (PEV)‐like placebo three times a day for 10 days (n = 119); penicillin V (PEV) megaunit (600 mg) three times a day for 10 days and CTM‐like placebo twice a day for 5 days (n = 125) ‐ Duration of treatment: 15 days ‐ Duration of follow‐up: 90 days
Outcomes	‐ Clinical outcomes: success = cure (complete resolution of fever and symptoms) on days 10 and 30 or improvement on day 10 and cure on day 30 without further antibiotics) ‐ Failure = no response to therapy on day 10, or improvement on day 10 but required further antibiotic or relapsed (recurrence of fever and/or symptoms), or cured on day 10 but subsequent relapse ‐ Relapse assessed on day 90 ‐ Adverse effects ‐ Bacteriological outcomes
Notes	‐ Funding: not reported ‐ Ethics approval: not mentioned ‐ Described as ITT analysis for efficacy, but post‐randomisation exclusions not included in analyses
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Reported as "randomised", but no description of randomisation sequence.
Allocation concealment (selection bias)	Unclear risk	Not described.
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Reported as "double blind, double dummy", but no description of how blinding of different administration frequency and duration was maintained.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Dropouts: 4 lost to follow‐up (all in penicillin group). no ITT analysis (although reported in table that ITT, the numbers do not correspond to ITT).
Selective reporting (reporting bias)	Unclear risk	Only clinical success reported, no specific symptoms; Adverse events reported, but no ITT analysis. 3 participants in each group discontinued because of adverse events.
Other bias	Unclear risk	Funding: not reported