Dai 2021.

Study characteristics
Methods
Participants	Inclusion criteria: "The patients, aged from 3 to 6 years old, were given the diagnosis of ASD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM‐5) , by a team of autism experts; Scores for Children Autism Rating Scale (CARS) were more than 30; Signed Informed Consents were provided by parents." Exclusion criteria: "Liver and kidney dysfunction; With a history of allergy to sulfa drugs; abnormal ECG; chromosomal abnormality; suffering from nervous system diseases (such as epilepsy, schizophrenia, and so on); using the melatonin treatment for sleep disorders or withdrawal less than three weeks." Location/setting: Shanghai, China Sample size: bumetanide 59; placebo 60 (119 in total) Reasons for withdrawals/dropouts: bumetanide 1 dropped out due to non‐adherence; placebo 2 dropped out (1 due to hand and foot disease, the other "met the criteria for withdrawal") Gender: bumetanide group 51 male, 8 female; placebo group 49 male, 11 female Mean age: bumetanide group 4.03 years; placebo 4.22 years IQ: details not provided except that 75% in the intervention and 65% placebo groups had ASD plus intellectual or developmental disability Baseline ABC‐I or other BoC scale: not an outcome Concomitant medications: details not provided Previous medications: details not provided
Interventions	Intervention (bumetanide) for 3 months: bumetanide tablets, oral intake, 0.5 mg, twice daily, respectively at 8 am and 4 pm Comparator (placebo) for 3 months: "placebo tablets, oral intake, 0.5 mg, twice daily, respectively at 8 am and 4 pm"
Outcomes	Primary outcomes: AEs Secondary outcomes: self‐injurious behaviour, change from baseline; measured using the Repetitive Behaviour Scale (Bodfish 2000) Timing of outcome assessments: not clear
Notes	Study start date: May 2017 Study end date: July 2019 Funding: various grants Conflicts of interest: details not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"Participants were randomly assigned in a 1:1 ratio to receive 0.5 mg oral bumetanide or placebo twice daily for 3 months by using a block randomization scheme." "The generation of random allocation sequence and the preparation of trial medication were done by investigators in an external consultancy who do not participate in other aspects of the study."
Allocation concealment (selection bias)	Unclear risk	"The study medication (bumetanide or placebo tablet) was provided in sequentially numbered envelopes"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"The study medication (bumetanide or placebo tablet) was provided in sequentially numbered envelopes"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Stated that "Patients and their caregivers, investigators, experienced psychiatrists, and data analysts remained masked to the treatment allocation until the study database was locked"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	1 withdrew because "they met the criteria for withdrawal"
Selective reporting (reporting bias)	Unclear risk	2 of the outcomes on the trial registry have not been reported.
Other bias	High risk	The baseline Repetitive Behaviour Scale (self‐injury) scores were double that in the placebo group.