Critical IllnessPhase 2KID-ICUNCT07639359
Subanesthetic Ketamine Infusions for Depressive Symptoms in Intensive Care Unit Patients
A Phase 2 study testing Ketamine (0.5 mg/kg) and Normal Saline (0.9% NaCl) in people with Critical Illness and Depressive Symptoms, run by Hospital Italiano de Buenos Aires at 2 sites in 2 countries.
Trial summary
Depressive symptoms are common among patients admitted to the intensive care unit (ICU) and may adversely affect recovery, participation in care, treatment adherence, quality of life, and outcomes after critical illness. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Critical Illness, Depressive Symptoms
- What is being tested?
- Ketamine (0.5 mg/kg) and Normal Saline (0.9% NaCl)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 14 May 2026to 1 Jun 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 to 99 years.
- Male or female.
- Admission to an intensive care unit for 6 or more days at the time of screening.
- Moderate to severe depressive symptoms, defined as a Patient Health Questionnaire-9 score of 10 or greater at screening.
- Ability to provide informed consent.
Who cannot join
- History of psychosis or hallucinations, as assessed by review of the electronic medical record and patient interview during screening.
- History of prolonged QT interval.
- History of dementia.
- History of major depressive disorder before the current intensive care unit admission.
- History of psychiatric diagnosis, including dissociative disorder, primary psychotic disorder, mania with psychosis, pervasive developmental disorder, cognitive disorder, or anorexia nervosa.
- Known allergy to ketamine or diphenhydramine.
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- History of increased intracranial pressure, hypertensive hydrocephalus, or increased intraocular pressure.
- Hemodynamic instability at the time of screening, defined as peripheral oxygen saturation <95%, systolic blood pressure <90 mmHg or >180 mmHg, heart rate <50 or >120 beats/min, or respiratory rate <10 or >30 breaths/min.
- Patient refusal to participate or to provide informed consent.
- Pregnancy, postpartum period within 2 months, or breastfeeding.
- Presence of intracranial mass or vascular lesion.
- Altered mental status precluding informed consent.
- Body weight >115 kg or <45 kg.
- Active psychosis.
- Current treatment with medications that may interfere with the N-methyl-D-aspartate receptor system, including lamotrigine, acamprosate, memantine, riluzole, or lithium.
- Current treatment with aminophylline or theophylline.
- Active substance withdrawal or use of hallucinogens, including cannabis, in the past month, as determined by clinical interview and urine drug screening.
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
United States1 site, 1 recruiting
- Recruiting
Mayo Clinic
Jacksonville, Florida, 32224
Devang K Sanghavi, MD, +13146408772, Sanghavi.Devang@mayo.edu
Devang K Sanghavi, MD
Argentina1 site, 1 recruiting
- Recruiting
Hospital Italiano de Buenos Aires - Sede Central
Buenos Aires, Buenos Aires
Ivan A Huespe, MD, +5493425382554, ivan.huespe@hospitalitaliano.org.ar
Ivan A Huespe, MD
About this study
Official title: Ketamine In Depression - Intensive Care Unit Trial (KID-ICU): A Phase II Randomized, Double-Blind, Placebo-Controlled Multicenter Study of Ketamine Infusion for Depressive Symptoms in Intensive Care Unit Patients
Depressive symptoms are common among patients admitted to the intensive care unit (ICU) and may adversely affect recovery, participation in care, treatment adherence, quality of life, and outcomes after critical illness. Conventional antidepressants have limited utility for rapidly treating depressive symptoms during an ICU admission because of their delayed onset of action and potential drug interactions in medically complex patients.
Ketamine is an N-methyl-D-aspartate receptor antagonist with rapid antidepressant effects when administered intravenously at subanesthetic doses. However, evidence regarding its efficacy and safety for depressive symptoms developing during critical illness remains limited.
Read more
The KID-ICU trial is a Phase II randomized, double-blind, placebo-controlled, multicenter trial evaluating subanesthetic intravenous ketamine for moderate-to-severe depressive symptoms in adult ICU patients. Eligible participants are adults who have been admitted to an ICU for 6 or more days and have a Patient Health Questionnaire-9 (PHQ-9) score of 10 or greater.
Participants will be randomized in a 1:1 ratio to receive either intravenous ketamine at 0.5 mg/kg, with a maximum dose of 60 mg per infusion, administered over 60 minutes once daily for 2 consecutive days, or normal saline placebo with an identical volume, appearance, and infusion duration.
The primary efficacy outcome is the change in PHQ-9 total score from baseline to Day 14 after the second scheduled infusion. Secondary outcomes include the longitudinal trajectory of PHQ-9 scores through Day 30, clinically meaningful PHQ-9 response at Day 14, anxiety and depressive symptoms assessed with the Hospital Anxiety and Depression Scale, Clinical Global Impression scores, prespecified safety events, time to ICU and hospital discharge alive, and 30-day all-cause mortality.
A total of 50 participants will be enrolled across participating ICUs in Argentina. Psychiatric and clinical follow-up will be provided to all participants regardless of treatment assignment.
Read the detailed description
Depressive symptoms are clinically relevant among patients with critical illness and may be exacerbated by acute illness, pain, immobility, sleep disruption, loss of autonomy, and prolonged hospitalization. These symptoms may negatively affect recovery, participation in care, treatment adherence, quality of life, and outcomes after critical illness.
Ketamine is an N-methyl-D-aspartate receptor antagonist with rapid antidepressant effects when administered at subanesthetic doses. In non-ICU populations, intravenous ketamine has been associated with early improvement in depressive symptoms. However, its efficacy and safety for depressive symptoms developing during critical illness remain uncertain.
KID-ICU is a Phase II randomized, double-blind, placebo-controlled, multicenter clinical trial with two parallel groups and 1:1 allocation. Eligible participants will be adult ICU patients with moderate-to-severe depressive symptoms, defined as a Patient Health Questionnaire-9 (PHQ-9) score of 10 or greater after 6 or more days of ICU admission. The PHQ-9 will be used to measure depressive symptom severity and not as a standalone diagnostic instrument for major depressive disorder.
Participants assigned to the ketamine group will receive intravenous ketamine at 0.5 mg/kg, with a maximum dose of 60 mg per infusion, administered over 60 minutes once daily for 2 consecutive days. Participants assigned to the placebo group will receive intravenous normal saline in an identical volume, appearance, and infusion duration. Study medication will be prepared by the research pharmacy in indistinguishable infusion bags.
Participants, care providers, investigators, and outcome assessors will remain blinded to treatment assignment. Only authorized unblinded research pharmacy personnel and the trial statistician responsible for generating or maintaining the allocation sequence will have access to treatment assignments. Emergency unblinding will be available through a predefined institutional procedure when knowledge of the assigned treatment is required for the clinical management of a serious or life-threatening event.
Randomization will be stratified by participating ICU site and implemented through the Research Electronic Data Capture randomization module. Treatment allocation will remain concealed until the database is locked, except when emergency unblinding is required.
Participants will undergo continuous clinical monitoring during and after each infusion, including heart rate, cardiac rhythm, blood pressure, peripheral oxygen saturation, respiratory status, and mental status. Adverse events will be assessed before, during, and after each infusion using clinical monitoring and the Ketamine Side Effect Tool. An infusion may be temporarily interrupted or permanently discontinued because of clinically significant hypertension, tachycardia, bradycardia, arrhythmia, respiratory deterioration, deterioration in consciousness, severe agitation, psychotic symptoms, or another serious adverse event according to prespecified criteria and investigator judgment.
Study assessments will be performed at baseline before the first infusion, before the second infusion, 24 hours after the second scheduled infusion, and at Days 7, 14, and 30 after the second scheduled infusion. Telephone follow-up will be permitted for participants discharged before completion of follow-up, using the same standardized outcome assessment procedures.
Depressive symptoms will be assessed with the PHQ-9. Anxiety and depressive symptoms will be assessed using the anxiety and depression subscales of the Hospital Anxiety and Depression Scale. Global clinical severity and improvement will be assessed using the Clinical Global Impression-Severity and Clinical Global Impression-Improvement scales.
The primary efficacy outcome is the change in PHQ-9 total score from baseline to Day 14 after the second scheduled infusion. Secondary outcomes include the longitudinal trajectory of PHQ-9 scores through Day 30, clinically meaningful PHQ-9 response at Day 14, longitudinal changes in Hospital Anxiety and Depression Scale subscale scores, Clinical Global Impression scores, prespecified treatment-emergent safety events, time to ICU discharge alive, time to hospital discharge alive, and all-cause mortality within 30 days after randomization.
The primary efficacy analysis will follow the intention-to-treat principle and compare PHQ-9 scores at Day 14 between treatment groups, adjusting for baseline PHQ-9 score and participating site. The treatment effect will be reported with a 95 percent confidence interval. Longitudinal PHQ-9 scores will be evaluated using a mixed-effects model including treatment group, categorical assessment time, and the treatment-by-time interaction. Time-to-discharge outcomes will account for death as a competing event. Secondary analyses will be considered exploratory.
All data will be collected prospectively using the Research Electronic Data Capture platform. Bedside assessments may initially be documented on paper source forms and subsequently transcribed into the electronic database. The planned sample size is 50 participants, with 25 participants assigned to each treatment group.
- Conditions
- Critical Illness, Depressive Symptoms
- Being tested
- Ketamine (0.5 mg/kg), Normal Saline (0.9% NaCl)
- Keywords
- ketamine, intensive care, Depressive Symptoms, Critical Illness, PHQ-9
- Medical subject headings
- Critical Illness, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketamine (0.5 mg/kg)Drug
Also called Ketalar, Ketamine hydrochloride
Ketamine hydrochloride for injection, diluted in 100 mL normal saline. Dose: 0.5 mg/kg (maximum 60 mg per infusion). Route: intravenous. Rate: infused over 40-60 minutes. Frequency: once daily. Duration: 2 consecutive days. Total maximum cumulative dose: 120 mg. Administered via peripheral or central venous catheter under continuous monitoring in the ICU.
Normal Saline (0.9% NaCl)Other
Normal saline (0.9% NaCl) in 100 mL bag, identical in appearance to the ketamine preparation. Infused over 40-60 minutes, once daily for 2 consecutive days. Administered via peripheral or central venous catheter.
| Study group | Role | What they receive |
|---|---|---|
| Ketamine | Experimental | Participants receive intravenous subanesthetic ketamine at 0.5 mg/kg (maximum 60 mg/day regardless of body weight), administered over 40-60 minutes, once daily for 2 consecutive days. The drug is prepared by the research pharmacy in bags visually identical to placebo. Administration via peripheral or central venous access with continuous hemodynamic monitoring. Receives: Drug: Ketamine (0.5 mg/kg) |
| Placebo | Placebo comparator | Participants receive intravenous normal saline (0.9% NaCl) prepared by the research pharmacy in bags visually identical to the ketamine preparation (same volume, color, and infusion duration of 40-60 minutes), once daily for 2 consecutive days. Identical hemodynamic monitoring and psychiatric assessment schedule as the experimental arm. Receives: Other: Normal Saline (0.9% NaCl) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in PHQ-9 Score from Baseline to Day 14 Post-Last Infusion
The Patient Health Questionnaire-9 (PHQ-9) is a validated 9-item self-report scale measuring the severity of depressive symptoms (score range 0-27; higher scores indicate greater severity). The primary efficacy endpoint is the change in PHQ-9 total score (ΔPHQ-9 = baseline score minus Day-14 score), where positive values indicate improvement.
Measured: From baseline (before first infusion, Day 0) to Day 14 after the last infusion
Incidence of Safety Events During and After Ketamine Infusion
Safety is assessed by the incidence of: (1) clinically significant hemodynamic instability requiring intervention (severe hypertension SBP ≥180 mmHg or DBP ≥110 mmHg requiring antihypertensives; sustained tachycardia ≥160 bpm; bradycardia <50 bpm; vasopressor initiation); (2) acute neuropsychiatric events (confusion, agitation, disorientation, dissociation, hallucinations, psychotic symptoms); (3) treatment discontinuation due to adverse events. Assessed using the Ketamine Side Effect Tool (KSET) and continuous monitoring.
Measured: During infusion and up to 240 minutes after each infusion (Days 1 and 2), and at follow-up visits (Days 1, 7, 14, and 30 post-last infusion)
Secondary outcomes (9)
Longitudinal Change in PHQ-9 Total Score Through Day 30 Post-Last Infusion
The PHQ-9 total score ranges from 0 to 27, with higher scores indicating greater depressive symptom severity. PHQ-9 scores will be assessed repeatedly at baseline, 24 hours, Day 7, Day 14, and Day 30 post-last infusion. Longitudinal trajectories will be compared between treatment groups. The analysis will estimate between-group differences in change from baseline at each follow-up time point and the overall treatment-by-time interaction.
Measured: Baseline, 24 hours, Day 7, Day 14, and Day 30 post-last infusion
PHQ-9 Response Rate (Sensitivity Analysis): Proportion Achieving ≥5-Point Reduction
Proportion of patients with a clinically significant improvement defined as a reduction of ≥5 points in PHQ-9 total score from baseline to Day 14
Measured: Baseline to Day 14 post-last infusion
Change From Baseline in Hospital Anxiety and Depression Scale Total Score at Day 14
The Hospital Anxiety and Depression Scale (HADS) is a 14-item participant-reported questionnaire assessing anxiety and depressive symptoms. Total scores range from 0 to 42, with higher scores indicating greater symptom severity. For each participant, change will be calculated as the baseline HADS total score minus the Day-14 score; therefore, positive values indicate improvement. The change in HADS total score will be compared between treatment groups, adjusting for baseline HADS score and participating site.
Measured: Time Frame: Baseline before the first infusion to Day 14 after the second scheduled infusion
Longitudinal Change in Hospital Anxiety and Depression Scale Total Score Through Day 30
The Hospital Anxiety and Depression Scale (HADS) is a 14-item participant-reported questionnaire assessing anxiety and depressive symptoms. Total scores range from 0 to 42, with higher scores indicating greater symptom severity. HADS total scores will be assessed repeatedly at baseline, 24 hours, Day 7, Day 14, and Day 30 after the second scheduled infusion. The analysis will estimate between-group differences in change from baseline at each follow-up assessment and the overall treatment-by-time interaction.
Measured: Baseline (Day 0, before first infusion), 24 hours, Day 7, Day 14, and Day 30 post-last infusion
Clinical Global Impression - Improvement Score
The Clinical Global Impression - Improvement scale is a clinician-rated instrument used to assess overall clinical improvement compared with baseline. The score ranges from 1 to 7, where 1 indicates "very much improved" and 7 indicates "very much worse." Scores will be compared between groups at each assessment point.
Measured: Infusion Day 2, 24 hours post-last infusion, Day 7, Day 14, and Day 30 post-last infusion.
Clinical Global Impression - Severity Score
The Clinical Global Impression - Severity scale is a clinician-rated instrument used to assess overall psychiatric illness severity. The score ranges from 1 to 7, where 1 indicates "normal, not at all ill" and 7 indicates "among the most extremely ill patients." Scores will be compared between groups at each assessment point.
Measured: Baseline, Infusion Day 1, Infusion Day 2, 24 hours post-last infusion, Day 7, Day 14, and Day 30 post-last infusion.
Intensive Care Unit Length of Stay
Number of days from randomization to Intensive Care Unit discharge
Measured: From the date of randomization to the date of Intensive Care Unit discharge, for up to 100 days
30-Day Mortality
Proportion of patients who die within 30 days of the last infusion
Measured: From randomization to hospital discharge or Day 30 post-last infusion, whichever comes first
Hospital length of stay
Number of days from randomization to hospital discharge, with death treated as a competing event
Measured: From the date of randomization to the date of hospital discharge, for up to 100 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2026
- Study start14 May 2026
- Primary completion1 May 2028 (estimated)
- Study completion1 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Critical IllnessStudies 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
- Two parallel groups (1:1 ratio): ketamine arm and placebo arm. Stratified randomization by participating ICU site. Double-blind: patients, care providers, and outcome assessors are blinded. Only the research pharmacist and trial statistician have access to the treatment allocation list.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Italiano de Buenos Aires
- Sponsor type
- University, hospital or other
- Collaborators
- Mayo Clinic
- Responsible party
- Principal investigator, Ivan A. Huespe, Hospital Italiano de Buenos Aires
- Investigators
- Ivan A Huespe, M.D., M.P.H., Principal investigator, Hospital Italiano de Buenos AiresDevang K Sanghavi, M.B.B.S., M.D., Study director, Mayo ClinicFederico Carini, M.D., Study chair, Hospital Italiano de Buenos Aires
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07639359
- Sponsor's protocol ID
- 7763
- Acronym
- KID-ICU
- Status last verified
- Aug 2026
- First submitted
- 1 Jun 2026
- Last updated
- 2 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Urtasun M, Daray FM, Teti GL, Coppolillo F, Herlax G, Saba G, Rubinstein A, Araya R, Irazola V. Validation and calibration of the patient health questionnaire (PHQ-9) in Argentina. BMC Psychiatry. 2019 Sep 18;19(1):291. doi: 10.1186/s12888-019-2262-9.
PubMed 31533674Rabiee A, Nikayin S, Hashem MD, Huang M, Dinglas VD, Bienvenu OJ, Turnbull AE, Needham DM. Depressive Symptoms After Critical Illness: A Systematic Review and Meta-Analysis. Crit Care Med. 2016 Sep;44(9):1744-53. doi: 10.1097/CCM.0000000000001811.
PubMed 27153046Bayes A, Short B, Zarate CA, Park L, Murrough JW, McLoughlin DM, Riva-Posse P, Schoevers R, Veraart J, Parikh S, Glue P, Fam J, McShane R, Galvez V, Martin D, Tor PC, Brunoni AR, Loo CK. The Ketamine Side Effect Tool (KSET): A comprehensive measurement-based safety tool for ketamine treatment in psychiatry. J Affect Disord. 2022 Jul 1;308:44-46. doi: 10.1016/j.jad.2022.04.020. Epub 2022 Apr 9.
PubMed 35405177Singh JB, Fedgchin M, Daly EJ, De Boer P, Cooper K, Lim P, Pinter C, Murrough JW, Sanacora G, Shelton RC, Kurian B, Winokur A, Fava M, Manji H, Drevets WC, Van Nueten L. A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression. Am J Psychiatry. 2016 Aug 1;173(8):816-26. doi: 10.1176/appi.ajp.2016.16010037. Epub 2016 Apr 8.
PubMed 27056608Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006 Aug;63(8):856-64. doi: 10.1001/archpsyc.63.8.856.
PubMed 16894061
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ketamine In Depression - Intensive Care Unit Trial (KID-ICU): A Phase II Randomized, Double-Blind, Placebo-Controlled Multicenter Study of Ketamine Infusion for Depressive Symptoms in Intensive Care Unit Patients
- ClinicalTrials.gov ID
- NCT07639359
- Acronym / sponsor ID
- KID-ICU / 7763
- Conditions
- Critical Illness, Depressive Symptoms
- Keywords
- ketamine, intensive care, Depressive Symptoms, Critical Illness, PHQ-9
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Hospital Italiano de Buenos AiresUniversity, hospital or other
- Collaborators
- Mayo Clinic
- Study start
- 14 May 2026 (actual)
- Primary completion
- 1 May 2028 (estimated)
- Study completion
- 1 Jun 2028 (estimated)
- First posted
- 10 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Depressive symptoms are common among patients admitted to the intensive care unit (ICU) and may adversely affect recovery, participation in care, treatment adherence, quality of life, and outcomes after critical illness. Conventional antidepressants have limited utility for rapidly treating depressive symptoms during an ICU admission because of their delayed onset of action and potential drug interactions in medically complex patients.
Ketamine is an N-methyl-D-aspartate receptor antagonist with rapid antidepressant effects when administered intravenously at subanesthetic doses. However, evidence regarding its efficacy and safety for depressive symptoms developing during critical illness remains limited.
The KID-ICU trial is a Phase II randomized, double-blind, placebo-controlled, multicenter trial evaluating subanesthetic intravenous ketamine for moderate-to-severe depressive symptoms in adult ICU patients. Eligible participants are adults who have been admitted to an ICU for 6 or more days and have a Patient Health Questionnaire-9 (PHQ-9) score of 10 or greater.
Participants will be randomized in a 1:1 ratio to receive either intravenous ketamine at 0.5 mg/kg, with a maximum dose of 60 mg per infusion, administered over 60 minutes once daily for 2 consecutive days, or normal saline placebo with an identical volume, appearance, and infusion duration.
The primary efficacy outcome is the change in PHQ-9 total score from baseline to Day 14 after the second scheduled infusion. Secondary outcomes include the longitudinal trajectory of PHQ-9 scores through Day 30, clinically meaningful PHQ-9 response at Day 14, anxiety and depressive symptoms assessed with the Hospital Anxiety and Depression Scale, Clinical Global Impression scores, prespecified safety events, time to ICU and hospital discharge alive, and 30-day all-cause mortality.
A total of 50 participants will be enrolled across participating ICUs in Argentina. Psychiatric and clinical follow-up will be provided to all participants regardless of treatment assignment.
Detailed description
Depressive symptoms are clinically relevant among patients with critical illness and may be exacerbated by acute illness, pain, immobility, sleep disruption, loss of autonomy, and prolonged hospitalization. These symptoms may negatively affect recovery, participation in care, treatment adherence, quality of life, and outcomes after critical illness.
Ketamine is an N-methyl-D-aspartate receptor antagonist with rapid antidepressant effects when administered at subanesthetic doses. In non-ICU populations, intravenous ketamine has been associated with early improvement in depressive symptoms. However, its efficacy and safety for depressive symptoms developing during critical illness remain uncertain.
KID-ICU is a Phase II randomized, double-blind, placebo-controlled, multicenter clinical trial with two parallel groups and 1:1 allocation. Eligible participants will be adult ICU patients with moderate-to-severe depressive symptoms, defined as a Patient Health Questionnaire-9 (PHQ-9) score of 10 or greater after 6 or more days of ICU admission. The PHQ-9 will be used to measure depressive symptom severity and not as a standalone diagnostic instrument for major depressive disorder.
Participants assigned to the ketamine group will receive intravenous ketamine at 0.5 mg/kg, with a maximum dose of 60 mg per infusion, administered over 60 minutes once daily for 2 consecutive days. Participants assigned to the placebo group will receive intravenous normal saline in an identical volume, appearance, and infusion duration. Study medication will be prepared by the research pharmacy in indistinguishable infusion bags.
Participants, care providers, investigators, and outcome assessors will remain blinded to treatment assignment. Only authorized unblinded research pharmacy personnel and the trial statistician responsible for generating or maintaining the allocation sequence will have access to treatment assignments. Emergency unblinding will be available through a predefined institutional procedure when knowledge of the assigned treatment is required for the clinical management of a serious or life-threatening event.
Randomization will be stratified by participating ICU site and implemented through the Research Electronic Data Capture randomization module. Treatment allocation will remain concealed until the database is locked, except when emergency unblinding is required.
Participants will undergo continuous clinical monitoring during and after each infusion, including heart rate, cardiac rhythm, blood pressure, peripheral oxygen saturation, respiratory status, and mental status. Adverse events will be assessed before, during, and after each infusion using clinical monitoring and the Ketamine Side Effect Tool. An infusion may be temporarily interrupted or permanently discontinued because of clinically significant hypertension, tachycardia, bradycardia, arrhythmia, respiratory deterioration, deterioration in consciousness, severe agitation, psychotic symptoms, or another serious adverse event according to prespecified criteria and investigator judgment.
Study assessments will be performed at baseline before the first infusion, before the second infusion, 24 hours after the second scheduled infusion, and at Days 7, 14, and 30 after the second scheduled infusion. Telephone follow-up will be permitted for participants discharged before completion of follow-up, using the same standardized outcome assessment procedures.
Depressive symptoms will be assessed with the PHQ-9. Anxiety and depressive symptoms will be assessed using the anxiety and depression subscales of the Hospital Anxiety and Depression Scale. Global clinical severity and improvement will be assessed using the Clinical Global Impression-Severity and Clinical Global Impression-Improvement scales.
The primary efficacy outcome is the change in PHQ-9 total score from baseline to Day 14 after the second scheduled infusion. Secondary outcomes include the longitudinal trajectory of PHQ-9 scores through Day 30, clinically meaningful PHQ-9 response at Day 14, longitudinal changes in Hospital Anxiety and Depression Scale subscale scores, Clinical Global Impression scores, prespecified treatment-emergent safety events, time to ICU discharge alive, time to hospital discharge alive, and all-cause mortality within 30 days after randomization.
The primary efficacy analysis will follow the intention-to-treat principle and compare PHQ-9 scores at Day 14 between treatment groups, adjusting for baseline PHQ-9 score and participating site. The treatment effect will be reported with a 95 percent confidence interval. Longitudinal PHQ-9 scores will be evaluated using a mixed-effects model including treatment group, categorical assessment time, and the treatment-by-time interaction. Time-to-discharge outcomes will account for death as a competing event. Secondary analyses will be considered exploratory.
All data will be collected prospectively using the Research Electronic Data Capture platform. Bedside assessments may initially be documented on paper source forms and subsequently transcribed into the electronic database. The planned sample size is 50 participants, with 25 participants assigned to each treatment group.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Two parallel groups (1:1 ratio): ketamine arm and placebo arm. Stratified randomization by participating ICU site. Double-blind: patients, care providers, and outcome assessors are blinded. Only the research pharmacist and trial statistician have access to the treatment allocation list.
| Arm | Type | Receives |
|---|---|---|
| Ketamine | Experimental | Drug: Ketamine (0.5 mg/kg)Participants receive intravenous subanesthetic ketamine at 0.5 mg/kg (maximum 60 mg/day regardless of body weight), administered over 40-60 minutes, once daily for 2 consecutive days. The drug is prepared by the research pharmacy in bags visually identical to placebo. Administration via peripheral or central venous access with continuous hemodynamic monitoring. |
| Placebo | Placebo comparator | Other: Normal Saline (0.9% NaCl)Participants receive intravenous normal saline (0.9% NaCl) prepared by the research pharmacy in bags visually identical to the ketamine preparation (same volume, color, and infusion duration of 40-60 minutes), once daily for 2 consecutive days. Identical hemodynamic monitoring and psychiatric assessment schedule as the experimental arm. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age 18 to 99 years.
- Male or female.
- Admission to an intensive care unit for 6 or more days at the time of screening.
- Moderate to severe depressive symptoms, defined as a Patient Health Questionnaire-9 score of 10 or greater at screening.
- Ability to provide informed consent.
Key exclusion criteria (17 listed)
- History of psychosis or hallucinations, as assessed by review of the electronic medical record and patient interview during screening.
- History of prolonged QT interval.
- History of dementia.
- History of major depressive disorder before the current intensive care unit admission.
- History of psychiatric diagnosis, including dissociative disorder, primary psychotic disorder, mania with psychosis, pervasive developmental disorder, cognitive disorder, or anorexia nervosa.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketamine (0.5 mg/kg)Also: Ketalar, Ketamine hydrochlorideKetamine hydrochloride for injection, diluted in 100 mL normal saline. Dose: 0.5 mg/kg (maximum 60 mg per infusion). Route: intravenous. Rate: infused over 40-60 minutes. Frequency: once daily. Duration: 2 consecutive days. Total maximum cumulative dose: 120 mg. Administered via peripheral or central venous catheter under continuous monitoring in the ICU. | Drug | Ketamine |
| Normal Saline (0.9% NaCl)Normal saline (0.9% NaCl) in 100 mL bag, identical in appearance to the ketamine preparation. Infused over 40-60 minutes, once daily for 2 consecutive days. Administered via peripheral or central venous catheter. | Other | Placebo |
Primary outcome
Change in PHQ-9 Score from Baseline to Day 14 Post-Last Infusion
Time frame: From baseline (before first infusion, Day 0) to Day 14 after the last infusion
The Patient Health Questionnaire-9 (PHQ-9) is a validated 9-item self-report scale measuring the severity of depressive symptoms (score range 0-27; higher scores indicate greater severity). The primary efficacy endpoint is the change in PHQ-9 total score (ΔPHQ-9 = baseline score minus Day-14 score), where positive values indicate improvement.
Incidence of Safety Events During and After Ketamine Infusion
Time frame: During infusion and up to 240 minutes after each infusion (Days 1 and 2), and at follow-up visits (Days 1, 7, 14, and 30 post-last infusion)
Safety is assessed by the incidence of: (1) clinically significant hemodynamic instability requiring intervention (severe hypertension SBP ≥180 mmHg or DBP ≥110 mmHg requiring antihypertensives; sustained tachycardia ≥160 bpm; bradycardia <50 bpm; vasopressor initiation); (2) acute neuropsychiatric events (confusion, agitation, disorientation, dissociation, hallucinations, psychotic symptoms); (3) treatment discontinuation due to adverse events. Assessed using the Ketamine Side Effect Tool (KSET) and continuous monitoring.
9 secondary outcomes
Longitudinal Change in PHQ-9 Total Score Through Day 30 Post-Last Infusion
Time frame: Baseline, 24 hours, Day 7, Day 14, and Day 30 post-last infusion
PHQ-9 Response Rate (Sensitivity Analysis): Proportion Achieving ≥5-Point Reduction
Time frame: Baseline to Day 14 post-last infusion
Change From Baseline in Hospital Anxiety and Depression Scale Total Score at Day 14
Time frame: Time Frame: Baseline before the first infusion to Day 14 after the second scheduled infusion
Longitudinal Change in Hospital Anxiety and Depression Scale Total Score Through Day 30
Time frame: Baseline (Day 0, before first infusion), 24 hours, Day 7, Day 14, and Day 30 post-last infusion
Clinical Global Impression - Improvement Score
Time frame: Infusion Day 2, 24 hours post-last infusion, Day 7, Day 14, and Day 30 post-last infusion.
Clinical Global Impression - Severity Score
Time frame: Baseline, Infusion Day 1, Infusion Day 2, 24 hours post-last infusion, Day 7, Day 14, and Day 30 post-last infusion.
Intensive Care Unit Length of Stay
Time frame: From the date of randomization to the date of Intensive Care Unit discharge, for up to 100 days
30-Day Mortality
Time frame: From randomization to hospital discharge or Day 30 post-last infusion, whichever comes first
Hospital length of stay
Time frame: From the date of randomization to the date of hospital discharge, for up to 100 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2026.
- Background: PubMed 31533674Urtasun M, Daray FM, Teti GL, Coppolillo F, Herlax G, Saba G, Rubinstein A, Araya R, Irazola V. Validation and calibration of the patient health questionnaire (PHQ-9) in Argentina. BMC Psychiatry. 2019 Sep 18;19(1):291. doi: 10.1186/s12888-019-2262-9.
- Background: PubMed 27153046Rabiee A, Nikayin S, Hashem MD, Huang M, Dinglas VD, Bienvenu OJ, Turnbull AE, Needham DM. Depressive Symptoms After Critical Illness: A Systematic Review and Meta-Analysis. Crit Care Med. 2016 Sep;44(9):1744-53. doi: 10.1097/CCM.0000000000001811.
- Background: PubMed 35405177Bayes A, Short B, Zarate CA, Park L, Murrough JW, McLoughlin DM, Riva-Posse P, Schoevers R, Veraart J, Parikh S, Glue P, Fam J, McShane R, Galvez V, Martin D, Tor PC, Brunoni AR, Loo CK. The Ketamine Side Effect Tool (KSET): A comprehensive measurement-based safety tool for ketamine treatment in psychiatry. J Affect Disord. 2022 Jul 1;308:44-46. doi: 10.1016/j.jad.2022.04.020. Epub 2022 Apr 9.
- Background: PubMed 27056608Singh JB, Fedgchin M, Daly EJ, De Boer P, Cooper K, Lim P, Pinter C, Murrough JW, Sanacora G, Shelton RC, Kurian B, Winokur A, Fava M, Manji H, Drevets WC, Van Nueten L. A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression. Am J Psychiatry. 2016 Aug 1;173(8):816-26. doi: 10.1176/appi.ajp.2016.16010037. Epub 2016 Apr 8.
- Background: PubMed 16894061Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006 Aug;63(8):856-64. doi: 10.1001/archpsyc.63.8.856.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ivan A Huespe, M.D., M.P.H. principal investigator
Hospital Italiano de Buenos Aires
Devang K Sanghavi, M.B.B.S., M.D. study director
Mayo Clinic
Federico Carini, M.D. study chair
Hospital Italiano de Buenos Aires
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ketamine (0.5 mg/kg) and Normal Saline (0.9% NaCl) in people with Critical Illness and Depressive Symptoms, run by Hospital Italiano de Buenos Aires at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Argentina. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ivan A. Huespe, M.D., M.P.H. (+5493425382554, ivan.huespe@hospitalitaliano.org.ar), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in PHQ-9 Score from Baseline to Day 14 Post-Last Infusion (time frame: From baseline (before first infusion, Day 0) to Day 14 after the last infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07639359, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2026.