Ketamine for Treatment Resistant Late-Life Depression

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT02556606
• Collaborator: (none)
• Enrollment: 33
• Location: 1
• Arms: 4
• Actual Duration (Months): 54
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to examine the effectiveness of a single infusion of ketamine (KET), to determine which dose is optimal 7 days after infusion using Bayesian Adaptive Randomization, and to learn about how ketamine works in the body and brain in persons with late-life treatment resistant depression.

Condition or Disease	Intervention/Treatment	Phase
Treatment Resistant Depressive Disorder	Drug: Ketamine; Drug: Ketamine; Drug: Ketamine; Drug: Midazolam	Phase 3

Detailed Description

Primary Aim: To identify the best performing condition across a single intravenous infusion of ketamine (KET) 0.1 mg/kg, KET 0.25 mg/kg, KET 0.50 mg/kg) and midazolam (MID) 0.03 mg/kg on Montgomery-Asberg Depression Rating Scale (MADRS) treatment response (at least a 50% improvement in depression from baseline) 7 days after the infusion in up to 72 Veterans with Late-Life Treatment Resistant Depression (LL-TRD) , using a triple blind (patient, rater, anesthesiologist) Bayesian adaptive randomization design.

Hypothesis 1: Single KET 0.5 mg/kg infusion is superior to KET 0.1 mg/kg, KET 0.25 mg/kg, and MID 0.03 mg/kg measured by the proportion of participants demonstrating > 50% reduction on MADRS scores 7 days post-treatment.

Secondary Aim: To evaluate the durability of day 7 treatment response across 3 sub-anesthetic doses of a single KET (0.1 mg/kg, 0.25 mg/kg, and 0.50 mg/kg) and MID (0.03 mg/kg) infusion in veterans with LL-TRD during a 4 week follow-up.

Hypothesis 2: a single KET 0.5 mg/kg infusion will be superior to a single infusion of KET 0.1 mg/kg, KET 0.25 mg/kg, and MID 0.03 mg/kg as measured by the proportion of participants demonstrating > 50% reduction on MADRS scores at 28 days post-infusion.

Tertiary Aim: To evaluate the immediate and longer-term safety and tolerability of the most effective KET infusion relative to MID in vets with LL-TRD.

Hypothesis 3: KET infusion at the most effective dose will be safe and well tolerated compared to MID, as assessed by psychoactive and general side effect rating scales during and up to 4 weeks post study infusion.

Exploratory Aims:

1. To measure the effects of the most effective dose of KET relative to MID on neurocognitive performance.

2. To measure the effects the most effective dose of KET relative to MID on peripheral biomarkers of cellular plasticity and inflammation.

3. To measure the effects the most effective dose of KET relative to MID on resting-state quantitative electroencephalography.

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: We use a Bayesian, adaptive, randomized design initially allocating subjects to 2 arms in a 1:3 ratio: ARM 1: MID 0.03 mg/kg (active placebo); ARM 2: four conditions KET 0.1 mg/kg, KET 0.25 mg/kg, KET 0.5 mg/kg or MID 0.03 mg/kg. After 1:1:1:1 allocation of the first 20 subjects to ARM 2, Bayesian adaptive randomization may stop for superiority, change randomization ratios and/or prune arms for futility based on the probability of a day 7 treatment response. ARM 1 remains open for allocation to ensure a placebo group sufficiently large for comparison with best dose KET. For analyses, MID of ARM 1 and ARM 2 will be combined so that there are 4 conditions (or arms) for final statistical analyses. We expected to enroll a maximum 72 patients.We use a Bayesian, adaptive, randomized design initially allocating subjects to 2 arms in a 1:3 ratio: ARM 1: MID 0.03 mg/kg (active placebo); ARM 2: four conditions KET 0.1 mg/kg, KET 0.25 mg/kg, KET 0.5 mg/kg or MID 0.03 mg/kg. After 1:1:1:1 allocation of the first 20 subjects to ARM 2, Bayesian adaptive randomization may stop for superiority, change randomization ratios and/or prune arms for futility based on the probability of a day 7 treatment response. ARM 1 remains open for allocation to ensure a placebo group sufficiently large for comparison with best dose KET. For analyses, MID of ARM 1 and ARM 2 will be combined so that there are 4 conditions (or arms) for final statistical analyses. We expected to enroll a maximum 72 patients.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Ketamine for Treatment Resistant Late-Life Depression
• Actual Study Start Date: Oct 1, 2015
• Actual Primary Completion Date: Mar 31, 2020
• Actual Study Completion Date: Mar 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ketamine 0.10 mg/kg randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg	Drug: Ketamine; randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg
Experimental: Ketamine 0.25 mg/kg randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg	Drug: Ketamine; randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg
Experimental: Ketamine 0.50 mg/kg randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg	Drug: Ketamine; randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg
Active Comparator: Midazolam 0.03 mg/kg randomly assigned to a single 40 min infusion of either MID 0.03mg/Kg	Drug: Midazolam; single 40 min infusion of MID 0.03mg/Kg

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Demonstrating at Least a 50% Reduction on Montgomery-Asberg Depression Rating Scale Scores [Day 7 post-infusion]

   To determine the best performing intervention among three sub-anesthetic doses of a single ketamine (0.1 mg/kg, 0.25 mg/kg, and 0.50 mg/kg) and midazolam (0.03 mg/kg) in Veterans with LL-TRD as measured by the percentage of participants demonstrating at least a 50% reduction from pre-treatment baseline on Montgomery-Asberg Depression Rating Scale (MADRS; score range 0 - 60, higher scores meaning more severe depression) scores at 7 days post-infusion.

Secondary Outcome Measures

1. Percentage of Patients With Continuation From Day 7 to Day 28 Post-infusion of at Least a 50% Improvement in MADRS [28 days post-infusion follow-up]

   Patients with a day 7 treatment response (at least a 50% improvement from baseline in Montgomery-Asberg Depression Rating Scale [MADRS]) are followed until day 28 post-infusion; day 7 non-responders are not followed. Outcome measure is the percentage of patients who continue to be responder at day 28, and is interpreted as a measure of durability of efficacy.

Other Outcome Measures

1. Change in Clinician-Administered Dissociative States Scale (CADSS) [Baseline to 40 minutes after start of infusion]

   Change from pre-infusion baseline to end of infusion at 40 minutes after start of infusion on the Clinician-Administered Dissociative States Scale (CADSS; scale form 0 [no psychosis-like symptoms] to 90 [severe psychosis-like symptoms]) to assess psychosis-like side effect on day of infusion.

2. Change in Resting-state Quantitative Electroencephalography (EEG) Frontal Gamma Band Power (Log of Microvolt Squared) [Baseline to 30 minutes after start of infusion]

   Change in EEG frontal gamma power from pre-infusion baseline to 30 minutes after start of infusion to assess engagement of the study drug with the N-methyl-D-aspartate receptor.

3. Change in Systolic Blood Pressure (Millimeters of Mercury, mm Hg) [Baseline to 30 minutes after start of infusion]

   Change in systolic blood pressure from pre-infusion baseline to 30 minutes after start of infusion

4. Change in Diastolic Blood Pressure (Millimeters of Mercury, mm Hg) [Baseline to 30 minutes after start of infusion]

   Change in systolic blood pressure from pre-infusion baseline to 30 minutes after start of infusion

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female patients, 55 years of age,

• Participants must fulfill DSM 5 criteria for a Major Depressive Episode (Unipolar), based on a structured diagnostic interview, the DSM 5 M.I.N.I. 7.0

• Participants must have a history of at least one previous episode of depression prior to the current episode (recurrent MDD) or have chronic MDD (of at least two years' duration),

• Participants have not responded to two or more adequate trials of FDA-approved antidepressants, determined by Antidepressant Treatment Response Questionnaire (ATRQ) criteria.

• Participants must score 14 or greater on the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR), and score 27 on the Montgomery Asberg Depression Rating Scale (MADRS),

• Each participant must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document.

Exclusion Criteria:

• Patients currently on fluoxetine,

• History of schizophrenia, schizoaffective disorder or any psychotic disorder, or bipolar disorder,

• Documented history of a psychotic disorder in a first-degree relative,

• Current diagnosis of obsessive-compulsive disorder (OCD) or eating disorder [bulimia nervosa or anorexia nervosa],

• Alcohol or substance use [except nicotine] within the preceding 6 months,

• Patients with any clinically significant personality disorder that would, in the investigator's judgment, preclude safe study participation,

• Patients judged to be at serious and imminent suicidal or homicidal risk,

• Serious, unstable medical illnesses including respiratory [obstructive sleep apnea, or history of difficulty with airway management during previous anesthetics], cardiovascular [including ischemic heart disease and uncontrolled hypertension], and neurologic [including history of severe head injury],

• For study entry, patients must be reasonable medical candidates for ketamine or midazolam infusion, as determined by a board-certified physician co-investigator during study Screening,

• Clinically significant abnormal findings of laboratory parameters [including urine toxicology screen for drugs of abuse], physical examination, or ECG,

• Hypertension (systolic BP >160 mm Hg or diastolic BP >90 mm Hg),

• Patients with one or more 11 seizures without a clear and resolved etiology,

• Patients starting hormonal treatment (e.g., estrogen) in the 3 months prior to Screening,

• Past intolerance or hypersensitivity to ketamine, or history of recreational use of phencyclidine (PCP) or ketamine,

• Past intolerance or hypersensitivity to midazolam,

• Age-related cognitive decline or mild dementia suggested by a score of < 25 on the Mini-Mental State Examination (MMSE) at Screening,

• Patients taking medications with known activity at the N-methyl-D-aspartate receptor (NMDA) or AMPA glutamate receptor [e.g., riluzole, amantadine, lamotrigine, memantine, topiramate, dextromethorphan, D-cycloserine], or the muopioid receptor,

• Patients taking any of the following medications: St John's Wort, theophylline, tramadol, metrizamide,

• Patients who demonstrate > 25% decrease in depressive symptoms as reflected by the QIDS-SR score from Screening to Randomization,

• Patients who have received electroconvulsive therapy (ECT) in the past 6 months prior to Screening,

• Patients currently receiving treatment with vagus nerve stimulation (VNS) or repetitive transcranial stimulation (rTMS).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Michael E. DeBakey VA Medical Center, Houston, TX	Houston	Texas	United States	77030

Sponsors and Collaborators

• VA Office of Research and Development

Investigators

• Principal Investigator: Sanjay Mathew, MD, Michael E. DeBakey VA Medical Center, Houston, TX

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 20, 2018

More Information

Publications

None provided.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT02556606
• Other Study ID Numbers: CLNA-001-14F
• First Posted: Sep 22, 2015
• Last Update Posted: Jan 11, 2022
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by VA Office of Research and Development: ketamine; depression; treatment resistant; treatment resistant depression; late life depression; depression in the elderly; geriatric depression
• Additional relevant MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Midazolam; Ketamine

Study Results

Participant Flow

Arm/Group Title	Ketamine 0.10 mg/kg	Ketamine 0.25 mg/kg	Ketamine 0.50 mg/kg	Midazolam 0.03 mg/kg
Arm/Group Description	randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg Ketamine: randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg	randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg Ketamine: randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg	randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg Ketamine: randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg	randomly assigned to a single 40 min infusion of either MID 0.03mg/Kg Midazolam: single 40 min infusion of MID 0.03mg/Kg
Period Title: Overall Study
STARTED	4	5	11	13
COMPLETED	4	5	11	13
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Ketamine 0.10 mg/kg	Ketamine 0.25 mg/kg	Ketamine 0.50 mg/kg	Midazolam 0.03 mg/kg	Total
Arm/Group Description	randomly assigned to a single 40 min infusion of KET 0.1 mg/kg	randomly assigned to a single 40 min infusion of KET 0.25 mg/kg	randomly assigned to a single 40 min infusion of KET 0.50 mg/kg	randomly assigned to a single 40 min infusion of MID 0.03 mg/kg	Total of all reporting groups
Overall Participants	4	5	11	13	33
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	66.75 (5.54)	61.8 (6.06)	60.91 (4.97)	62.15 (5.54)	62.24 (5.60)
Sex: Female, Male (Count of Participants)
Female	0 0%	3 60%	3 27.3%	4 30.8%	10 30.3%
Male	4 100%	2 40%	8 72.7%	9 69.2%	23 69.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 20%	0 0%	1 7.7%	2 6.1%
Not Hispanic or Latino	4 100%	4 80%	11 100%	12 92.3%	31 93.9%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	2 50%	3 60%	4 36.4%	7 53.8%	16 48.5%
White	2 50%	2 40%	7 63.6%	6 46.2%	17 51.5%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Demonstrating at Least a 50% Reduction on Montgomery-Asberg Depression Rating Scale Scores
Description	To determine the best performing intervention among three sub-anesthetic doses of a single ketamine (0.1 mg/kg, 0.25 mg/kg, and 0.50 mg/kg) and midazolam (0.03 mg/kg) in Veterans with LL-TRD as measured by the percentage of participants demonstrating at least a 50% reduction from pre-treatment baseline on Montgomery-Asberg Depression Rating Scale (MADRS; score range 0 - 60, higher scores meaning more severe depression) scores at 7 days post-infusion.
Time Frame	Day 7 post-infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine 0.10 mg/kg	Ketamine 0.25 mg/kg	Ketamine 0.50 mg/kg	Midazolam 0.03 mg/kg
Arm/Group Description	randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg Ketamine: randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg	randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg Ketamine: randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg	randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg Ketamine: randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg	randomly assigned to a single 40 min infusion of either MID 0.03mg/Kg Midazolam: single 40 min infusion of MID 0.03mg/Kg
Measure Participants	4	5	11	13
Count of Participants [Participants]	0 0%	2 40%	8 72.7%	6 46.2%

2. Secondary Outcome

Title	Percentage of Patients With Continuation From Day 7 to Day 28 Post-infusion of at Least a 50% Improvement in MADRS
Description	Patients with a day 7 treatment response (at least a 50% improvement from baseline in Montgomery-Asberg Depression Rating Scale [MADRS]) are followed until day 28 post-infusion; day 7 non-responders are not followed. Outcome measure is the percentage of patients who continue to be responder at day 28, and is interpreted as a measure of durability of efficacy.
Time Frame	28 days post-infusion follow-up

Outcome Measure Data

Analysis Population Description

Day 7 responders were followed until day 28 post-infusion or until relapse

Arm/Group Title	Ketamine 0.10 mg/kg	Ketamine 0.25 mg/kg	Ketamine 0.50 mg/kg	Midazolam 0.03 mg/kg
Arm/Group Description	randomly assigned to a single 40 min infusion of KET 0.1 mg/kg	randomly assigned to a single 40 min infusion of KET 0.25 mg/kg	randomly assigned to a single 40 min infusion of KET 0.50 mg/kg	randomly assigned to a single 40 min infusion of MID 0.03 mg/kg
Measure Participants	0	2	8	6
Count of Participants [Participants]	0 0%	1 20%	7 63.6%	4 30.8%

3. Other Pre-specified Outcome

Title	Change in Clinician-Administered Dissociative States Scale (CADSS)
Description	Change from pre-infusion baseline to end of infusion at 40 minutes after start of infusion on the Clinician-Administered Dissociative States Scale (CADSS; scale form 0 [no psychosis-like symptoms] to 90 [severe psychosis-like symptoms]) to assess psychosis-like side effect on day of infusion.
Time Frame	Baseline to 40 minutes after start of infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine 0.10 mg/kg	Ketamine 0.25 mg/kg	Ketamine 0.50 mg/kg	Midazolam 0.03 mg/kg
Arm/Group Description	randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg Ketamine: randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg	randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg Ketamine: randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg	randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg Ketamine: randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg	randomly assigned to a single 40 min infusion of either MID 0.03mg/Kg Midazolam: single 40 min infusion of MID 0.03mg/Kg
Measure Participants	4	5	11	13
Pre-infusion baseline	1.41 (0.71)	0 (0)	0.09 (0.30)	0.23 (0.60)
End of infusion at 40 minutes	4.79 (2.39)	14.98 (6.70)	21.36 (20.53)	4.38 (6.73)

4. Other Pre-specified Outcome

Title	Change in Resting-state Quantitative Electroencephalography (EEG) Frontal Gamma Band Power (Log of Microvolt Squared)
Description	Change in EEG frontal gamma power from pre-infusion baseline to 30 minutes after start of infusion to assess engagement of the study drug with the N-methyl-D-aspartate receptor.
Time Frame	Baseline to 30 minutes after start of infusion

Outcome Measure Data

Analysis Population Description

Missing data due to poor data quality for KET 0.1 (n=1), KET 0.5 (n=3) or MID (n=3)

Arm/Group Title	Ketamine 0.10 mg/kg	Ketamine 0.25 mg/kg	Ketamine 0.50 mg/kg	Midazolam 0.03 mg/kg
Arm/Group Description	randomly assigned to a single 40 min infusion of KET 0.1 mg/kg	randomly assigned to a single 40 min infusion of KET 0.25 mg/kg	randomly assigned to a single 40 min infusion of KET 0.50 mg/kg	randomly assigned to a single 40 min infusion of MID 0.03 mg/kg
Measure Participants	3	5	8	10
Pre-infusion baseline	0.0019 (0.0004)	0.055 (0.0030)	0.0042 (0.0026)	0.0061 (0.0078)
30 minutes after start of infusion	0.0035 (0.0012)	0.0057 (0.0044)	0.0098 (0.0067)	0.004 (0.0027)

5. Other Pre-specified Outcome

Title	Change in Systolic Blood Pressure (Millimeters of Mercury, mm Hg)
Description	Change in systolic blood pressure from pre-infusion baseline to 30 minutes after start of infusion
Time Frame	Baseline to 30 minutes after start of infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine 0.10 mg/kg	Ketamine 0.25 mg/kg	Ketamine 0.50 mg/kg	Midazolam 0.03 mg/kg
Arm/Group Description	randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg Ketamine: randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg	randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg Ketamine: randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg	randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg Ketamine: randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg	randomly assigned to a single 40 min infusion of either MID 0.03mg/Kg Midazolam: single 40 min infusion of MID 0.03mg/Kg
Measure Participants	4	5	11	13
Pre-infusion baseline	154.25 (5.91)	142.2 (15.97)	132.91 (10.56)	125.54 (213.01)
30 minutes after start of infusion	152.75 (12.97)	148.2 (18.07)	160.36 (25.94)	116.62 (15.56)

6. Other Pre-specified Outcome

Title	Change in Diastolic Blood Pressure (Millimeters of Mercury, mm Hg)
Description	Change in systolic blood pressure from pre-infusion baseline to 30 minutes after start of infusion
Time Frame	Baseline to 30 minutes after start of infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine 0.10 mg/kg	Ketamine 0.25 mg/kg	Ketamine 0.50 mg/kg	Midazolam 0.03 mg/kg
Arm/Group Description	randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg Ketamine: randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg	randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg Ketamine: randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg	randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg Ketamine: randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg	randomly assigned to a single 40 min infusion of either MID 0.03mg/Kg Midazolam: single 40 min infusion of MID 0.03mg/Kg
Measure Participants	4	5	11	13
Pre-infusion baseline	80.5 (7.05)	74.6 (13.37)	82.64 (4.72)	72.23 (9.36)
30 minutes after start of infusion	91.25 (14.24)	82.6 (18.53)	95.45 (16.01)	73.54 (12.29)

Adverse Events

Time Frame	28 days
Arm/Group Title	Ketamine 0.10 mg/kg		Ketamine 0.25 mg/kg		Ketamine 0.50 mg/kg		Midazolam 0.03 mg/kg
Arm/Group Description	randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg Ketamine: randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg		randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg Ketamine: randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg		randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg Ketamine: randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg		randomly assigned to a single 40 min infusion of either MID 0.03mg/Kg Midazolam: single 40 min infusion of MID 0.03mg/Kg
All Cause Mortality
	Ketamine 0.10 mg/kg		Ketamine 0.25 mg/kg		Ketamine 0.50 mg/kg		Midazolam 0.03 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/5 (0%)		0/11 (0%)		0/13 (0%)
Serious Adverse Events
	Ketamine 0.10 mg/kg		Ketamine 0.25 mg/kg		Ketamine 0.50 mg/kg		Midazolam 0.03 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/5 (0%)		0/11 (0%)		1/13 (7.7%)
Psychiatric disorders
Suicide attempt	0/4 (0%)	0	0/5 (0%)	0	0/11 (0%)	0	1/13 (7.7%)	1
Other (Not Including Serious) Adverse Events
	Ketamine 0.10 mg/kg		Ketamine 0.25 mg/kg		Ketamine 0.50 mg/kg		Midazolam 0.03 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		5/5 (100%)		11/11 (100%)		13/13 (100%)
Cardiac disorders
Cardiac complaints	1/4 (25%)	1	3/5 (60%)	3	4/11 (36.4%)	4	7/13 (53.8%)	7
Eye disorders
Eye or ear complaints	3/4 (75%)	3	5/5 (100%)	5	4/11 (36.4%)	4	11/13 (84.6%)	11
Gastrointestinal disorders
Gastrointestinal complaints	4/4 (100%)	4	4/5 (80%)	4	8/11 (72.7%)	8	11/13 (84.6%)	11
General disorders
Sleep complaints	4/4 (100%)	4	5/5 (100%)	5	11/11 (100%)	11	13/13 (100%)	13
Other complaints	4/4 (100%)	4	5/5 (100%)	5	11/11 (100%)	11	13/13 (100%)	13
Nervous system disorders
Nervous system complaints	4/4 (100%)	4	5/5 (100%)	5	7/11 (63.6%)	7	11/13 (84.6%)	11
Reproductive system and breast disorders
Genital or urinary complaints	2/4 (50%)	2	3/5 (60%)	3	5/11 (45.5%)	5	6/13 (46.2%)	6
Sexual functioning complaints	3/4 (75%)	3	4/5 (80%)	4	9/11 (81.8%)	9	12/13 (92.3%)	12
Skin and subcutaneous tissue disorders
Skin complaints	4/4 (100%)	4	5/5 (100%)	5	7/11 (63.6%)	7	9/13 (69.2%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.