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
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.
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 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.
Time frame
From baseline (before first infusion, Day 0) to Day 14 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
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.
Time frame
Baseline, 24 hours, Day 7, Day 14, and Day 30 post-last infusion2
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
Time frame
Baseline to Day 14 post-last infusion3
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.
Time frame
Time Frame: Baseline before the first infusion to Day 14 after the second scheduled infusion4
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.
Time frame
Baseline (Day 0, before first infusion), 24 hours, Day 7, Day 14, and Day 30 post-last infusionSponsors and contacts
Click on the lead sponsor to view all of their trials.
Hospital Italiano de Buenos Aires
Lead sponsor
Mayo Clinic
Collaborator
Source ClinicalTrials.gov