Suicidal IdeationPhase 2NCT07888933
Intravenous Ketamine for Acute Suicidal Crisis and Psychiatric Hospital Length of Stay
A Phase 2 study testing Esketamine and Midazolam (Intravenous) in people with Suicidal Ideation and Suicidal Behavior, run by University of Sao Paulo at 1 site in Brazil.
Trial summary
This randomized, double-blind, active placebo-controlled superiority trial will evaluate whether intravenous esketamine reduces time to psychiatric hospital discharge in adults hospitalized because of acute suicide risk. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Suicidal Ideation, Suicidal Behavior
- What is being tested?
- Esketamine and Midazolam (Intravenous)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 106 participants
- Where
- 1 siteBrazil
- Study dates
- 30 Apr 2027to 30 Mar 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years.
- Psychiatric hospitalization because of suicide risk.
- Acute suicidal ideation, defined as a Scale for Suicide Ideation (SSI) score >3.
- Ability to understand the study procedures and provide written informed consent.
- Willingness to participate in the study.
Who cannot join
- Current diagnosis of schizophrenia or another psychotic disorder.
- Active substance use disorder within the previous 6 months, except caffeine or nicotine.
- Known contraindication to esketamine, including severe hypertension, previous stroke, intracranial hypertension, porphyria, or known hypersensitivity to the study drug.
- Pregnancy or breastfeeding.
- Unstable medical condition or clinically relevant cardiovascular risk.
- Participation in another clinical trial within the previous 3 months.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil1 site
Institute of Psychiatry, Hospital das Clínicas, University of São Paulo Medical School
São Paulo, São Paulo
About this study
Official title: Intravenous Ketamine for the Management of Acute Suicidal Crisis: Effect on Psychiatric Hospital Length of Stay - A Randomized, Double-Blind, Active Placebo-Controlled Superiority Trial
This randomized, double-blind, active placebo-controlled superiority trial will evaluate whether intravenous esketamine reduces time to psychiatric hospital discharge in adults hospitalized because of acute suicide risk. A total of 106 participants will be randomized in a 1:1 ratio to receive intravenous esketamine or midazolam as an active placebo. Participants assigned to esketamine will receive eight 40-minute intravenous infusions at a dose of 0.5 mg/kg administered twice weekly. The primary outcome is time from the first study infusion to psychiatric hospital discharge. Secondary outcomes include suicidal ideation and behavior, depressive symptoms, psychological pain, hopelessness, global clinical improvement, safety, tolerability, dissociative symptoms, and healthcare costs. Exploratory analyses will investigate peripheral inflammatory markers, BDNF, and polygenic risk scores as potential predictors or mediators of treatment response. Clinical follow-up will continue through Week 12.
Read the detailed description
Acute suicidal crises frequently require psychiatric hospitalization and are associated with substantial morbidity, mortality, and healthcare utilization. Conventional antidepressant treatments may require several weeks to achieve clinically meaningful effects, creating an important therapeutic gap during periods of acute suicide risk. Rapid-acting glutamatergic interventions may therefore provide an important therapeutic option during this critical period.
This is a single-center, randomized, double-blind, active placebo-controlled superiority trial conducted at the Institute of Psychiatry, Hospital das Clínicas, University of São Paulo Medical School (IPq-HCFMUSP), São Paulo, Brazil. Adults hospitalized because of suicide risk and presenting with acute suicidal ideation will be randomized in a 1:1 ratio using permuted blocks stratified by psychiatric diagnosis.
Participants assigned to the experimental group will receive eight intravenous infusions of esketamine at a dose of 0.5 mg/kg administered over 40 minutes twice weekly. Participants assigned to the control group will receive intravenous midazolam 0.045 mg/kg as an active placebo. Participants, investigators, and outcome assessors will remain blinded to treatment allocation.
Eligible participants must be enrolled within 72 hours after hospital admission. Following written informed consent and baseline assessments, the first study infusion will be administered within 24 hours after randomization. For the primary analysis, time zero will be defined as the first study infusion.
The primary objective is to determine whether intravenous esketamine reduces time to psychiatric hospital discharge compared with active placebo. Secondary objectives include evaluating remission and severity of suicidal ideation, suicidal behavior, depressive symptoms, psychological pain, hopelessness, global clinical improvement, safety and tolerability, dissociative symptoms, and healthcare costs. Clinical follow-up will continue through Week 12. Exploratory analyses will assess inflammatory biomarkers, BDNF, and genetic markers as potential predictors or mediators of treatment response.
- Conditions
- Suicidal Ideation, Suicidal Behavior
- Being tested
- Esketamine, Midazolam (Intravenous)
- Keywords
- Acute suicidal crisis, Suicide risk, Esketamine, Psychiatric hospitalization, Suicidal ideation, Suicide prevention, Rapid-acting treatment, Psychiatric hospital length of stay
- Medical subject headings
- Suicidal Ideation, Suicide Prevention
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EsketamineDrug
ntravenous esketamine 0.5 mg/kg diluted in 100 mL of 0.9% saline, administered over 40 minutes twice weekly for a total of eight infusions.
Midazolam (Intravenous)Drug
Intravenous midazolam 0.045 mg/kg diluted in 0.9% saline and administered as an active placebo.
| Study group | Role | What they receive |
|---|---|---|
| Intravenous Esketamine | Experimental | Participants will receive eight intravenous esketamine infusions at a dose of 0.5 mg/kg administered over 40 minutes twice weekly. Esketamine will be diluted in 100 mL of 0.9% saline and administered using a volumetric infusion pump. Blood pressure, heart rate, oxygen saturation, and cardiac rhythm will be monitored during and after each infusion. Receives: Drug: Esketamine |
| Midazolam Active Placebo | Placebo comparator | Participants will receive intravenous midazolam at a dose of 0.045 mg/kg diluted in 0.9% saline. Midazolam is used as an active placebo to improve maintenance of masking. Blood pressure, heart rate, oxygen saturation, and cardiac rhythm will be monitored during and after the infusion. Receives: Drug: Midazolam (Intravenous) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Psychiatric Hospital Discharge
Time, in days, from the first study infusion to discharge from the index psychiatric hospitalization. Hospital discharge will be considered the event of interest. Participants who do not experience the event during the observation period will be censored at the last date for which outcome information is available. Time to discharge will be compared between participants randomized to intravenous esketamine and participants randomized to active placebo.
Measured: From the first study infusion until discharge from the index psychiatric hospitalization, assessed up to 6 months.
Secondary outcomes (15)
Remission of Suicidal Ideation at 72 Hours
Proportion of participants achieving complete remission of suicidal ideation, defined as a Scale for Suicide Ideation (SSI) score ≤3.
Measured: 72 hours after the first study infusion
Change in Suicidal Ideation Severity
Change in clinician-rated and self-rated Scale for Suicide Ideation (SSI) scores from baseline across treatment and follow-up assessments. Higher scores indicate greater severity of suicidal ideation.
Measured: Baseline through Week 12
Suicidal Ideation and Behavior During Follow-up
Change in suicidal ideation and occurrence of suicidal behavior assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS).
Measured: Baseline through Week 12
Suicide Attempts During Follow-up
Number and proportion of participants experiencing at least one suicide attempt during clinical follow-up.
Measured: From the first study infusion through Week 12
Change in Depressive Symptoms Assessed by PHQ-9
Change in Patient Health Questionnaire-9 total score from baseline. Higher scores indicate greater severity of depressive symptoms.
Measured: Baseline through Week 12
Change in Depressive Symptoms Assessed by QIDS-SR
Change in Quick Inventory of Depressive Symptomatology-Self-Report total score from baseline.
Measured: Baseline through Week 12
Change in Clinician-Rated Depressive Symptoms
Change in Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) total score from baseline.
Measured: Baseline through Week 12
Change in Psychological Pain
Change in Psychological Pain Visual Analog Scale (PPP-VAS) score from baseline.
Measured: Baseline through Week 12
Change in Hopelessness
Change in Beck Hopelessness Scale (BHS) total score from baseline. Higher scores indicate greater hopelessness.
Measured: Baseline through Week 12
Clinical Global Improvement
Overall clinical improvement assessed using the Clinical Global Impression-Improvement (CGI-I) scale.
Measured: Through Week 12
Change in Manic Symptoms
Change in Young Mania Rating Scale (YMRS) total score during treatment and follow-up.
Measured: Baseline through Week 12
Change in General Psychiatric Symptoms
Change in Brief Psychiatric Rating Scale (BPRS) total score during treatment and follow-up.
Measured: Baseline through Week 12
Dissociative Symptoms
Severity of dissociative symptoms assessed using the Clinician-Administered Dissociative States Scale (CADSS) after the first study infusion and at weeks 1, 2, 4, 6 and 12.
Measured: After the first study infusion and at weeks 1, 2, 4, 6 and 12.
Treatment-Emergent Adverse Events
Incidence and severity of adverse events occurring during study treatment and clinical follow-up.
Measured: From the first study infusion through Week 12
Treatment-Related Healthcare Costs
Healthcare costs associated with the index psychiatric hospitalization, medications, and psychotherapeutic treatments.
Measured: From the first study infusion through Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2026
- Study start30 Apr 2027 (estimated)
- Primary completion30 Jan 2029 (estimated)
- Study completion30 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Suicidal IdeationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomly assigned in a 1:1 ratio to receive intravenous esketamine or intravenous midazolam as an active placebo. Randomization will use permuted blocks and will be stratified by psychiatric diagnosis.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 106 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daniel Costa, University of Sao Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07888933
- Sponsor's protocol ID
- KET-SUICIDE-IPQ-2026-01
- Status last verified
- Oct 2026
- First submitted
- 7 Oct 2026
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Sajid S, Mann JJ, Grunebaum MF. Clinical trials since 2020 of rapid anti-suicidal ideation effects of ketamine and its enantiomers: a systematic review. Transl Psychiatry. 2025 Feb 6;15(1):44. doi: 10.1038/s41398-025-03255-0.
PubMed 39915491Jollant F, Colle R, Nguyen TML, Corruble E, Gardier AM, Walter M, Abbar M, Wagner G. Ketamine and esketamine in suicidal thoughts and behaviors: a systematic review. Ther Adv Psychopharmacol. 2023 Feb 7;13:20451253231151327. doi: 10.1177/20451253231151327. eCollection 2023.
PubMed 36776623Grunebaum MF, Galfalvy HC, Choo TH, Keilp JG, Moitra VK, Parris MS, Marver JE, Burke AK, Milak MS, Sublette ME, Oquendo MA, Mann JJ. Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial. Am J Psychiatry. 2018 Apr 1;175(4):327-335. doi: 10.1176/appi.ajp.2017.17060647. Epub 2017 Dec 5.
PubMed 29202655Abbar M, Demattei C, El-Hage W, Llorca PM, Samalin L, Demaricourt P, Gaillard R, Courtet P, Vaiva G, Gorwood P, Fabbro P, Jollant F. Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial. BMJ. 2022 Feb 2;376:e067194. doi: 10.1136/bmj-2021-067194.
PubMed 35110300