Objective: To evaluate the effectiveness of screening and ultra-brief intervention (Ultra-BI) delivered by primary care physicians in less than 1 minute compared to simplified assessment only (SAO) for reducing alcohol consumption among patients with hazardous drinking. Design: Pragmatic, cluster randomised, parallel-group, superiority trial. We used a computer-generated random sequence to allocate clusters. Only participants and personnel who collected participant-reported outcomes remained blinded. Setting: 40 primary care clinics in Japan, which did not provide routine screening and brief intervention for hazardous drinking, treatment, or self-help groups for alcohol dependence. Participants: 1,133 outpatients aged 20-74 years with hazardous drinking (scores of Alcohol Use Disorders Identification Test-Consumption [AUDIT-C] ≥5 for men and ≥4 for women). Patients who were pregnant or suspected of having COVID-19-like symptoms were excluded. Interventions: Clusters were randomised to Ultra-BI (21 clusters, n=531) or SAO (19 clusters, n=602) groups. Ultra-BI comprised screening with AUDIT, brief oral advice, and an alcohol information leaflet. SAO involved only simplified assessment with AUDIT-C. Main outcome measures: The primary outcome was total alcohol consumption in the preceding 4 weeks (TAC) at 24 weeks post-randomisation. Secondary outcomes included TAC at 12 weeks and readiness to change drinking habits at 12 and 24 weeks. Results: At 24 weeks, the difference in TAC between Ultra-BI (1046.9g/4 weeks, 95% confidence interval [CI] 918.3-1175.4) and SAO (1019.0g/4 weeks, 95% CI 893.5-1144.6) groups was 27.8g/4 weeks (95% CI -149.7 to 205.4). Bayes factor analysis (0.08 ± 0.25) strongly supported the null hypothesis for TAC at 24 weeks. Ultra-BI group showed higher readiness to change drinking habits at both 12 (difference 0.30 [95% CI 0.10 to 0.40]; Hedge's g 0.21 [95% CI 0.10 to 0.33]) and 24 weeks (difference 0.20 [95% CI 0.10 to 0.30]; Hedge's g 0.16 [95% CI 0.05 to 0.28]). Conclusions: This trial did not support the effectiveness of Ultra-BI for alcohol consumption compared to SAO, but did improve readiness to change compared to SAO. These findings call for developing effective, low-cost interventions in primary care settings. Trial registration: UMIN000051388

Ryuhei So and Hiroki Nishimura were employed by CureApp, Inc. during the conduct of the study. Ryuhei So received institutional grants from the Osake-no-Kagaku Foundation and the Mental Health Okamoto Memorial Foundation. He holds multiple pending patents (JP2022049590A, US20220084673A1, JP2022178215A, JP2022070086, JP2023074128A). Sachio Matsushita received personal fees from CureApp, Inc., Otsuka Pharmaceutical Co., Ltd., EA Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., Yoshitomi Pharmaceutical Industries, Ltd., Eisai Co., Ltd., Nippon Shinyaku Co., Ltd., and MSD K.K. outside the submitted work. Toshi A. Furukawa reports personal fees from Boehringer-Ingelheim, Daiichi Sankyo, DT Axis, Micron, Shionogi, SONY and UpToDate, and a grant from DT Axis and Shionogi, outside the submitted work; In addition, Toshi A. Furukawa has a patent 7448125 and a pending patent 2022-082495, and has licensed intellectual properties for Kokoro-app to Mitsubishi-Tanabe. Yukio Tezuka received lecture fees from MSD K.K. outside the submitted work. Yoshinori Horie, Hitoshi Yoshiji received personal fees from CureApp, Inc. and Otsuka Pharmaceutical Co., Ltd., outside the submitted work. Takefumi Yuzuriha received personal fees from CureApp, Inc., Otsuka Pharmaceutical Co., Ltd., and Nippon Shinyaku Co., Ltd., outside the submitted work. Kazuhiro Nouso received personal fees from CureApp, Inc. for coordinating a pivotal study outside the submitted work. All other authors declare no competing interests.

UMIN000051388

The EASY study was conducted with a grant from the Japan Agency for Medical Research and Development (AMED) (23he0122018j0003), awarded to the consortium comprising CureApp, Inc., the Kurihama Medical and Addiction Center, and Okayama City Hospital. AMED had no involvement in any aspect of the study process.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study protocol, including these procedures, was approved by the institutional review board of the Kurihama Medical and Addiction Center on May 22, 2023 (registration number: 423).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors.