NAIA3003.

Methods	Randomised, double‐blind, placebo‐controlled, multicentre trial investigating the efficacy and safety of inhaled zanamivir compared with standard care in controlling outbreaks of influenza in nursing homes
Participants	Participants in nursing homes were randomised when healthy and followed until an outbreak of influenza was declared in that nursing home
Interventions	Zanamivir 2 inhalations (5 mg per inhalation) once a day plus 1 placebo tablet once a day Placebo 2 inhalations once a day plus 1 rimantadine tablet (100 mg) once a day
Outcomes	Primary outcome: the proportion of randomised participants who, during prophylaxis, developed a new sign or symptom and had laboratory confirmation of influenza infection Secondary outcomes: The proportion of randomised participants who, during prophylaxis, developed febrile illness The proportion of randomised participants who, during prophylaxis (days 1 to 15) or anytime during the study (days 1 to 28), developed complications of influenza and had subsequent associated laboratory confirmation of influenza infection The proportion of randomised participants who, during prophylaxis (days 1 to 15) or anytime during the study (days 1 to 28), took an antibiotic due to complications of influenza and had subsequent associated laboratory confirmation of influenza infection The proportion of randomised participants who, during days 3 to 15 of prophylaxis, developed a new sign or symptom with subsequent associated laboratory confirmation of influenza infection The proportion of randomised participants who, during prophylaxis, had laboratory‐confirmed influenza infection
Notes	4 protocol amendments were made and do not appear to have any influence on the outcomes. Adverse event data were not extracted from this study because of exposure to rimantadine
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Method of sequence generation not specified
Allocation concealment (selection bias)	Low risk	Pharmacy‐controlled randomisation
Incomplete outcome data (attrition bias) Symptoms	Low risk	All randomised participants included in ITT for efficacy
Incomplete outcome data (attrition bias) Complications of influenza	Low risk	All randomised participants included in ITT for efficacy
Incomplete outcome data (attrition bias) Safety data	Low risk	All who took at least 1 dose of medication included in ITT for safety
Selective reporting (reporting bias)	Low risk	Outcomes were reported as specified in the protocol and analysis plan
Other bias	High risk	2 protocol amendments for interim safety analysis; some re‐randomisation of patients occurred
Blinding of participants and personnel (performance bias) All outcomes	High risk	No certificates of analysis were provided
Blinding of outcome assessment (detection bias) All outcomes	Low risk	This study was double‐blind. As such, the investigators, participants and study monitors were unaware of which treatment a participant was randomly assigned to receive. Breaking of the code by opening the hidden portion of the detachable drug label was expressly forbidden except in the event of a medical emergency where the identity of the drug was necessary in order to treat the participant properly