Fonseca‐Aten 2006.

Methods	Design: randomised double‐blind placebo‐controlled trial Duration: trial endpoint of 5 days. Post‐treatment follow‐up carried out for 3 to 8 weeks Setting: trial participants initially treated in an emergency department setting. Trial carried out in the United States
Participants	Population: 43 children with an acute exacerbation of asthma were randomised to receive clarithromycin (n = 22) or placebo (n = 21), in both cases in addition to normal care Age: participants ranged in age from 4 to 15 years. Age range in the clarithromycin group was 5 to 15 years, and age range in the placebo group was 4 to 15 years Inclusion criteria: presentation for evaluation within 72 hours of the start of an acute exacerbation of asthma Exclusion criteria: children with diagnosed bacterial infection needing antibiotics; children with contraindications to clarithromycin administration or with drug interactions with clarithromycin; renal impairment; pregnancy; treatment with antibiotics or systemic steroids within 2 weeks before presentation; chronic lung conditions (other than asthma) or chronic systemic illnesses. Participants were also excluded following randomisation if they did not attend follow‐up visits 1 and 2 in the specified periods Percentage withdrawn: withdrawal from the clarithromycin group was 36.4%; withdrawal from the placebo group was 33.3% Allowed medication: none recorded Disallowed medication: none recorded
Interventions	Clarithromycin group: participants received 15 mg/kg, in 2 divided doses, to a maximum of 500 mg twice daily for 5 days Placebo group: participants received a placebo twice daily for 5 days. No further information given
Outcomes	Primary endpoints were comparison of nasal cytokine and chemokine concentrations, and serum cytokines, between the 2 arms. The secondary endpoint was a comparison between the 2 groups on the presence or absence of Chlamydia pneumoniae and Mycoplasma pneumoniae infection at each of the 2 follow‐up visits
Notes	Type of publication: peer‐reviewed Funding: study supported in part by grants from Abbott Laboratories Inc and Children's Medical Centre of Dallas Research Advisory Committee Contact: unsuccessful attempts made to contact study authors to seek further information about clinical outcomes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Study authors described the study as randomised but gave no further details
Allocation concealment (selection bias)	Unclear risk	"Abbott Laboratories Inc (Abbott Park, IL) provided formulations of clarithromycin and placebo to the Children's Medical Center at Dallas pharmacy for randomisation and distribution to patients" However, it is not clear if packs were identical, and if investigators would be able determine assignment
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Study authors stated that it was a "double‐blind placebo controlled" study
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No specific details were given regarding outcome assessor blinding
Incomplete outcome data (attrition bias) All outcomes	High risk	More than 50% of participants did not complete follow‐up; therefore status is unknown
Selective reporting (reporting bias)	High risk	No prospective registration was identified, and not all evaluated outcomes were reported numerically, e.g. "No clinical differences were demonstrated for clarithromycin therapy vs placebo on visit 3"
Other bias	Low risk	No other source of bias was identified