Esketamine Versus Crisis Response Planning Versus Enhanced Treatment as Usual for Suicide Prevention: A Pragmatic Randomized Trial in a Brazilian Municipality (SAVE)

NCT07120477 · tracked via the Priya Life Science Brazil tracker

Sponsor

University of Sao Paulo

Phase

Phase 4

Started

2026-06-01

Last updated

2026-09-16

Condition(s) studied

Suicide PreventionKetamineCrisis Response Plan

Investigational drug(s) / intervention(s)

Intravenous Esketamine →Crisis Response Planning (CRP)Enhanced Treatment as Usual (eTAU)

Intravenous Esketamine: A single intravenous esketamine infusion of 0.375 mg/kg is administered over 40 minutes in a monitored medical setting. Monitoring includes blood pressure, ECG, and oxygen saturation, with structured safety assessments during the infusion and for 4 hours afterward. Administration is supervised by trained medical staff with emergency support available. Clinical observation continues, with discharge after 24 hours if clinically stable. Subsequent assessments follow the study assessment schedule.

Crisis Response Planning (CRP): A single 20-to-45-minute Crisis Response Planning (CRP) session is delivered by a trained clinician. The clinician and participant collaboratively develop a personalized plan identifying warning signs, internal coping strategies, reasons for living, social support contacts, and professional and emergency resources. Participants receive a printed plan and a digital copy. Clinicians receive standardized training and supervision, and intervention delivery is documented using a fidelity checklist.

Enhanced Treatment as Usual (eTAU): eTAU comprises early outpatient psychiatric consultation within 7 days of randomization and lethal means safety counseling during the index emergency attendance. Both components are offered in every randomized arm alongside routine emergency care. The consultation is arranged through CAPS or CEEM. During lethal means safety counseling, a trained team member collaborates with the participant on a plan to reduce access to potentially lethal means. Completion and dates of both components are recorded separately, together with reasons for non-completion. Consultation attendance is verified at the Day 7 assessment (T2) and through municipal service records; appointment booking alone is not counted as consultation delivery. Treating clinicians remain responsible for clinical care.

Study summary

The SAVE study will test whether a single esketamine infusion or a single Crisis Response Planning session, each added to enhanced treatment as usual, reduces future suicide-related events compared with enhanced treatment as usual alone. The study takes place in the public emergency care network of Indaiatuba, São Paulo, Brazil, and includes adolescents and adults aged 14 years or older who have attempted suicide within the previous 30 days or currently have severe suicidal thoughts with intent to act.

The main questions are whether either intervention reduces suicide-related events over 12 months and whether the interventions improve suicidal thoughts, depression, anxiety, sleep, well-being, hopelessness, and quality of life. Researchers will also evaluate acceptability, feasibility, use of health services, and costs.

Anticipated total enrollment is 478 participants: 10 participants in a separate pilot cohort and 468 in the main cohort used to test the study hypotheses. The main cohort will be assigned by chance, in equal numbers of 156 participants, to one of three groups:

1. Esketamine plus enhanced treatment as usual: one intravenous infusion of esketamine at 0.375 mg/kg over 40 minutes, with medical supervision and monitoring of heart rhythm, blood pressure, and oxygen levels. Participants remain under clinical observation, with discharge after 24 hours if clinically stable.
2. Crisis Response Planning plus enhanced treatment as usual: one 20-to-45-minute session with a trained clinician to develop a personalized plan covering warning signs, coping strategies, reasons for living, support contacts, and emergency resources. Participants receive a printed plan and a digital copy.
3. Enhanced treatment as usual alone: early outpatient psychiatric consultation, arranged to take place within seven days of randomization, plus lethal means safety counseling to reduce access to potentially lethal means. Both components are offered to participants in all three groups, alongside routine emergency care. The study records whether each component was delivered; booking a consultation alone does not count as receiving it.

Participants will complete assessments at enrollment, 24 hours, seven days, and weeks 2, 4, 8, 16, 24, 32, 40, and 52. Blood samples will be collected at enrollment for exploratory analyses of biological factors that may be associated with treatment response. Safety monitoring and contact to identify new events will continue throughout follow-up.

Participants will also use a smartphone application to answer brief questions about their mood, thoughts, and experiences during three periods of 30 consecutive days, beginning at enrollment and at calendar months 4 and 8. There will be three prompts each day: two at fixed times, 09:00 and 21:00, and one at a randomly selected time between 10:00 and 20:00, using local time in Indaiatuba. This represents 90 assessment days and 270 scheduled prompts over the study. The study team will contact participants within 24 hours of a safety alert through a dedicated study mobile phone with WhatsApp. Participants will be instructed to seek emergency care immediately when needed rather than wait for a study response.

The main outcome is the time to the first qualifying event: a suicide attempt, including an attempt stopped by the person or interrupted by someone else; a psychiatric admission to prevent suicide; death by suicide; or self-injury requiring emergency department care. An external adjudicator who does not know the assigned treatment will review suspected events and determine whether they meet the study definition. Outcome assessors will also be unaware of treatment allocation.

Participants who experience a qualifying event may be offered rescue treatment combining esketamine and Crisis Response Planning, depending on clinical eligibility and safety. They will remain in follow-up and in analyses according to their original randomized group. The first qualifying event will still count in the main analysis. Pilot data will be described separately and will not be included in confirmatory efficacy analyses.

Eligibility

Sex

ALL

Min age

14 Years

Max age

—

Healthy volunteers

Inclusion Criteria: Participants must meet all of the following criteria: 1. Age 14 years or older. 2. Presentation to a participating public emergency service (ED/UEU) in Indaiatuba, São Paulo, Brazil. 3. Either of the following: 1. A suicide attempt within the previous 30 days, including an actual, interrupted, or aborted attempt; OR 2. Current severe suicidal ideation, defined as endorsement of item 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) screening version: active suicidal ideation with intent to act, without a specific plan (item 4), or with a specific plan (item 5). Non-suicidal self-injury alone does not satisfy this criterion. 4. Residence within the study catchment area in Indaiatuba, enabling completion of follow-up assessments. 5. Ability to provide written informed consent for participants aged 18 years or older, or written assent with written informed consent from a parent or legal guardian for participants aged 14-17 years. 6. No clinical decision for voluntary or involuntary admission to a psychiatric inpatient unit following the index emergency evaluation. Exclusion Criteria: Participants meeting any of the following criteria are excluded: 1. A contraindication to esketamine, including aneurysmal vascular disease, arteriovenous malformation, a history of intracerebral hemorrhage, or known hypersensitivity to esketamine or ketamine. 2. Current pregnancy or breastfeeding. Pregnancy testing is performed in the emergency setting for participants with pregnancy potential; breastfeeding status is established by clinical history. 3. Medical instability requiring intensive care unit admission without feasible study follow-up. 4. A primary psychotic disorder, such as schizophrenia or schizoaffective disorder; or current acute psychosis or an acute manic episode that precludes informed participation. 5. Any of the following substance-related conditions: 1. Acute intoxication at assessment that precludes valid informed consent, reliable administration of the C-SSRS, or safe delivery of the assigned intervention, as determined by the attending physician. Re-screening is permitted after clinical recovery if all other eligibility criteria remain satisfied. For participants qualifying on the basis of a recent suicide attempt, that attempt must still fall within the preceding 30 days. 2. High-risk hallucinogen involvement, defined as a WHO ASSIST substance-specific involvement score of 27 or higher for the hallucinogen category, item (h). 3. A documented history of ketamine use disorder identified during baseline psychiatric assessment. 6. Inability to maintain contact for follow-up assessments. Substance-use assessment: The Brazilian Portuguese WHO ASSIST is administered during baseline eligibility assessment. Substance-specific involvement scores are calculated from questions 2 through 7, with question 5 omitted for tobacco. Questions 1 and 8 do not contribute to these scores. High risk is defined as a score of 27 or higher. The ASSIST hallucinogen category does not identify ketamine exposure specifically; relevant substance history is also assessed clinically. Except for the high-risk hallucinogen criterion above, ASSIST scores do not automatically exclude participation. Among eligible participants, high-risk involvement with alcohol or other non-tobacco substances is recorded for exploratory moderation analyses and to inform clinical care.

Primary outcome measure(s)

Time to first event — One year from randomization
Time from randomization to the first suicide-related event: an actual, interrupted, or aborted suicide attempt; suicide-preventive psychiatric admission; suicide death; or self-injury requiring emergency department care. Events are identified through structured C-SSRS interviews, medical record linkage, and routine clinical surveillance. An external adjudicator blinded to treatment allocation reviews treatment-redacted source documentation to confirm whether each event meets the endpoint definition, its component and date, and whether multiple reports refer to the same episode. Suicidal intent and event components are recorded separately. The confirmatory analysis uses Cox proportional-hazards models, with Holm family-wise error control for esketamine plus eTAU versus eTAU and CRP plus eTAU versus eTAU. The 10 pilot participants are excluded from confirmatory efficacy analyses and reported descriptively.

Trial sites (1)

Facility	City	Region	Status
Prefeitura de Indaiatuba	Indaiatuba	São Paulo	Recruiting

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07120477 on ClinicalTrials.gov ↗ ← All trials in Brazil