Recruiting
Phase 2

Ketamine

Sponsor:

Hospital Italiano de Buenos Aires

Code:

NCT07639359

Conditions

Critical Illness

Depressive Symptoms

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Ketamine (0.5 mg/kg)

Normal Saline (0.9% NaCl)

Study Details

Brief 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. 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.

Conditions

Critical Illness

Depressive Symptoms

Study ID

NCT07639359

Start date

May 14, 2026

Status verified date

Aug, 2026

Completion date

Jun 1, 2028

Anticipated

Primary completion date

May 1, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

\*\*Inclusion Criteria:\*\*

  • 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.

\*\*Exclusion Criteria:\*\*

  • 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.
  • 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.

Study Design

Enrollment

50 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Ketamine

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 comparator: Placebo

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.

Interventions

Ketamine (0.5 mg/kg)

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)

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.

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 ]
  • 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) ]

Central Contacts and Locations

Central contacts

Ivan A. Huespe, M.D., M.P.H.

+5493425382554ivan.huespe@hospitalitaliano.org.ar

Locations

Mayo Clinic

Recruiting

Jacksonville, Florida, United States, 32224

Contacts

Devang K Sanghavi, MD

+13146408772Sanghavi.Devang@mayo.edu

Principal Investigator:

Devang K Sanghavi, MD

More Information

Sponsor

Hospital Italiano de Buenos Aires

Last update posted

Sep 2, 2026

Last verified

Aug, 2026

Keywords

  • ketamine
  • intensive care
  • Depressive Symptoms
  • Critical Illness
  • PHQ-9

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Hospital Italiano de Buenos Aires on 2026-09-02.