RecruitingPhase 4
Esketamine Versus Crisis Response Planning Versus Enhanced Treatment as Usual for Suicide Prevention: A Pragmatic Randomized Trial in a Brazilian Municipality (SAVE)
NCT07120477 · SAVE · University of Sao Paulo
Recruiting
Status
Accepting participants
Phase 4
Phase
478
Target enrolment
1
Study sites
Outside the US
What it is testing
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.
Summary as written by the trial’s own sponsor and published on ClinicalTrials.gov API v2. It is the sponsor’s description, reproduced unedited, not an assessment by this site.
What counts as success
Primary outcome measures
Time to first event
Measured over One year from randomization
A trial succeeds or fails on its primary outcome, declared in advance. Everything else it reports is secondary by definition.
Who can take part
Eligibility, as published
14 Years
Ages
All
Sex
Not accepted
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.
Where
1 study site
| Facility | City | Region | Country |
|---|---|---|---|
| Prefeitura de Indaiatuba | Indaiatuba | São Paulo | Brazil |
On the registry
Contact the trial directly
This site does not enrol anyone and is not involved in this trial. To ask about taking part, use the sponsor’s own contact details on the official registry record. The registry also holds the most current version of everything above.
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NCT07120477 on ClinicalTrials.gov →
Last updated in the registry 2026-09-16. Registry records change; this page reflects the data build of 2026-10-06.
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