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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Change in PHQ-9 Score from Baseline to Day 14 Post-Last Infusion
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •**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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Ketamine (0.5 mg/kg) (Drug)
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.
干预措施: Normal Saline (0.9% NaCl) (Other)
结局指标
主要结局
Change in PHQ-9 Score from Baseline to Day 14 Post-Last Infusion
时间窗: 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.
次要结局
- Longitudinal Change in PHQ-9 Total Score Through Day 30 Post-Last Infusion(Baseline, 24 hours, Day 7, Day 14, and Day 30 post-last infusion)
- PHQ-9 Response Rate (Sensitivity Analysis): Proportion Achieving ≥5-Point Reduction(Baseline to Day 14 post-last infusion)
- Change From Baseline in Hospital Anxiety and Depression Scale Total Score at Day 14(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(Baseline (Day 0, before first infusion), 24 hours, Day 7, Day 14, and Day 30 post-last infusion)
研究者
Ivan A. Huespe
Head of the Section of Critical Care Research and Innovation
Hospital Italiano de Buenos Aires