Crutel 2020.

Study name	Bumetanide oral liquid formulation for the treatment of children and adolescents with autism spectrum disorder: design of two phase III studies (SIGN Trials)
Methods	6‐month parallel trial of bumetanide versus placebo
Participants	Inclusion criteria: "a primary diagnosis of ASD as per DSM‐5 criteria, plus ASD criteria met on ADOS‐2 and ADI‐R", aged 7‐17 years (study 1) or 2‐6 years (study 2), moderate to severe ASD according to CGI score of at least 4, CARS2 total score of at least 34 Exclusion criteria: "concomitant participation in another study, or previous participation in a study of another medicinal product for 3 months prior to enrollment; known monogenic syndrome (e.g. Fragile X, Rett Syndrome); high suicide risk or psychiatric conditions considered likely to interfere with the conduct of the study; chronic hepatic disease, renal dysfunction or cardiac dysfunction; unstable psychotherapy, behavioral, cognitive, or cognitive‐behavioral therapy; concomitant psychotropic medication (exceptions: aripiprazole and risperidone in study 1, which are permitted if a stable dose is used between selection and inclusion, and up to Week 26; methylphenidate, atomoxetine, or guanfacine, which are permitted in both studies if stabilized for at least 4 weeks prior to inclusion and not planned to be modifed or stopped up to Week 26) or other contraindicated medication; and previous treatment with bumetanide that was not effective for the treatment of ASD symptoms" Setting/ location: across 13 countries Sample size: 170 per trial
Interventions	Intervention (bumetanide) for 6 months: oral solution of 0.04 mL/kg twice daily for participants weighing < 25 kg; participants ≥ 25 kg will receive 0.5 mg twice daily Comparator (placebo) for 6 months: equivalent placebo, twice daily depending on weight
Outcomes	Primary outcomes: AEs Secondary outcomes: QoL measured using the Pediatric Quality of Life Inventory (Varni 2001) and the WHOQoL (WHO 1998). Timing of outcome assessments: unclear
Starting date	Unclear
Contact information	Simon Kyaga E‐mail: simon.kyaga@servier.com
Notes	Source of funding: Servier (pharmaceutical company) Conflicts of interest: most study authors are employees of the funder (pharmaceutical company)