Subanesthetic Ketamine Infusions for Depressive Symptoms in Intensive Care Unit Patients

NCT07639359 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 7763
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 2

Brief Summary

\*\*Brief Summary\*\* Depressive symptoms are frequent among patients admitted to the intensive care unit (ICU) and may be associated with worse clinical outcomes, reduced participation in care, lower treatment adherence, and increased mortality. Conventional antidepressants, including selective serotonin reuptake inhibitors (SSRIs), have limited utility in this setting because of their delayed onset of action, incomplete efficacy, and potential drug interactions in medically complex patients. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has emerged as a rapid-acting antidepressant when administered at subanesthetic doses. Preliminary evidence suggests that intravenous ketamine may improve mood-related symptoms within a short time frame and may have an acceptable safety profile in selected critically ill patients. The KID-ICU trial (Ketamine In Depression - Intensive Care Unit) is a Phase II randomized, double-blind, placebo-controlled multicenter trial designed to evaluate the efficacy and safety of subanesthetic intravenous ketamine infusions for moderate-to-severe depressive symptoms in adult ICU patients. Eligible participants are adults who have been admitted to the ICU for 6 or more days and have moderate-to-severe depressive symptoms, defined as 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 day, administered over 40 to 60 minutes on 2 consecutive days, or placebo with normal saline in an identical presentation. The primary efficacy outcome is the change in PHQ-9 score from baseline to Day 30 after the last infusion. Safety outcomes include prespecified hemodynamic, neuropsychiatric, and treatment-discontinuation events during and after infusion. Secondary outcomes include anxiety and depression symptoms assessed with the Hospital Anxiety and Depression Scale (HADS), clinical severity and improvement assessed with Clinical Global Impression scales, intensive care unit and hospital length of stay, and mortality. A total of 50 participants will be enrolled across intensive care unit sites at Hospital Italiano de Buenos Aires. Psychiatric and clinical follow-up will be provided to all participants regardless of treatment assignment.

Conditions

Depression Disorder; Ketamine

Keywords

ketamine; intensive care; depression

Outcome Measures

Primary Outcomes (2)

• Change in PHQ-9 Score from Baseline to Day 30 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-30 score), where positive values indicate improvement.

  From baseline (before first infusion, Day 0) to Day 30 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.

  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 (7)

• Clinical Response Rate on Hospital Anxiety and Depression Scale (HADS)

  Baseline (Day 0, before first infusion), 24 hours, Day 7, Day 14, and Day 30 post-last infusion

• Clinical Global Impression - Severity Score

  Baseline, Infusion Day 1, Infusion Day 2, 24 hours post-last infusion, Day 7, Day 14, and Day 30 post-last infusion.

• Clinical Global Impression - Improvement Score

  Infusion Day 2, 24 hours post-last infusion, Day 7, Day 14, and Day 30 post-last infusion.

• Intensive Care Unit Length of Stay

  From the date of randomization to the date of Intensive Care Unit discharge, for up to 100 days

• 30-Day Mortality

  From randomization to hospital discharge or Day 30 post-last infusion, whichever comes first

Study Arms (2)

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.

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.

Other: Normal Saline (0.9% NaCl)

Interventions

Ketamine (0.5 mg/kg) DRUG

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.

Also known as: Ketalar, Ketamine hydrochloride

Ketamine

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Hospital Italiano de Buenos Aires: lead

Study Sites (2)

Mayo Clinic

Jacksonville, Florida, 32224, United States

RECRUITING

Hospital Italiano de Buenos Aires - Sede Central

Buenos Aires, Buenos Aires, Argentina

RECRUITING

Related Publications (2)

• Zwettler FU, Spindler MC, Reinhard S, Klein T, Kurz A, Benavente R, Sauer M. Tracking down the molecular architecture of the synaptonemal complex by expansion microscopy. Nat Commun. 2020 Jun 26;11(1):3222. doi: 10.1038/s41467-020-17017-7.

  PMID: 32591508 BACKGROUND

• Tang-Siegel GG, Chen C, Mintz KP. Increased sensitivity of Aggregatibacter actinomycetemcomitans to human serum is mediated by induction of a bacteriophage. Mol Oral Microbiol. 2023 Feb;38(1):58-70. doi: 10.1111/omi.12378. Epub 2022 Jul 25.

  PMID: 35833243 BACKGROUND

MeSH Terms

Conditions

Depression

Interventions

Ketamine; Saline Solution

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Ivan A Huespe, MD

  Hospital Italiano de Buenos Aires

  PRINCIPAL INVESTIGATOR

• Devang K Sanghavi, M.B.B.S., M.D.

  Mayo Clinic

  STUDY DIRECTOR

• Federico Carini, M.D.

  Hospital Italiano de Buenos Aires

  STUDY CHAIR

Central Study Contacts

Ivan IH Huespe, MD

CONTACT

+5493425382554; ivan.huespe@hospitalitaliano.org.ar

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The research pharmacy prepares and dispenses identical-appearing bags for both ketamine and normal saline. Ketamine is diluted so that both preparations are visually indistinguishable. The clinical team administering the infusion and assessing outcomes is fully blinded. Emergency unblinding is available to the treating physician in case of a life-threatening adverse event via a sealed envelope system.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of the Section of Critical Care Research and Innovation

Model Details: 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.

Study Record Dates

• First Submitted: June 1, 2026
• First Posted: June 10, 2026
• Study Start: May 14, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: June 10, 2026

Record last verified: 2026-06

Locations

US (1); AR (1)