Subanesthetic Ketamine Infusions for Depressive Symptoms in Intensive Care Unit Patients
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-99
SponsorHospital Italiano de Buenos Aires
About this trial
\*\*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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Ketamine (0.5 mg/kg)
DrugKetamine 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 interventionNormal 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.
Treatment groups
50 Participants
are divided into 2 treatment groupsGroup A: KetamineExperimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
From baseline (before first infusion, Day 0) to Day 30 after the last infusion2
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.
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)Secondary outcomes
1
Clinical Response Rate on Hospital Anxiety and Depression Scale (HADS)
Proportion of patients achieving ≥50% reduction in HADS total score from baseline, assessed at each follow-up visit. HADS is a 14-item validated scale (range 0-42; higher scores indicate greater anxiety/depression severity)
Time frame
Baseline (Day 0, before first infusion), 24 hours, Day 7, Day 14, and Day 30 post-last infusion2
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.
Time frame
Baseline, Infusion Day 1, Infusion Day 2, 24 hours post-last infusion, Day 7, Day 14, and Day 30 post-last infusion.3
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.
Time frame
Infusion Day 2, 24 hours post-last infusion, Day 7, Day 14, and Day 30 post-last infusion.4
Intensive Care Unit Length of Stay
Number of days from randomization to Intensive Care Unit discharge
Time frame
From the date of randomization to the date of Intensive Care Unit discharge, for up to 100 daysSponsors and contacts
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Source ClinicalTrials.gov