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| ID | Type | Description | Link |
|---|---|---|---|
| 271201100006I-0-27100007-1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
| Baylor College of Medicine | OTHER |
| Icahn School of Medicine at Mount Sinai | OTHER |
| Stanford University |
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This study is looking at the efficacy, durability, safety, and tolerability of multiple single doses of Ketamine vs. active placebo for treating patients with treatment resistant depression who are taking an antidepressant that is not working for them.
The primary objective is to investigate whether all doses (0.1 mg/kg, 0.2 mg/kg, 0.5 mg/kg, and 1.0 mg/kg) of ketamine are superior to active placebo (midazolam 0.045 mg/kg) therapy in the acute treatment of patients with treatment resistant depression within 72 hours (Day 3), when added to ongoing and stable antidepressant therapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ketamine 0.1mg | Active Comparator | Patients in this arm will receive 0.1 mg/kg of Ketamine - one single infusion |
|
| Ketamine 0.2mg | Active Comparator | Patients in this arm will receive 0.2 mg/kg of Ketamine - one single infusion |
|
| Ketamine 0.5mg | Active Comparator | Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion |
|
| Ketamine 1.0mg | Active Comparator | Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion |
|
| Midazolam (Active Placebo) | Placebo Comparator | Patients in this arm will receive 0.045 mg/kg of midazolam - one single infusion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ketamine | Drug | Dose of Ketamine will be 0.1 mg/kg - one single infusion |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Hamilton Rating Scale for Depression - 6 Items | The HAMD6 is a 6-item clinician-rated scale, where clinicians rate the presence of depression symptoms (i.e., depressed mood, guilt, work and interests, psychomotor retardation, psychic anxiety, somatic symptoms) on a 5-point scale, where 0 = not present, and 1-4 represent increasingly severe symptoms. One item (i.e., somatic symptoms) is rated on only a 3-point scale, ranging from 0-2. The possible scale range is 0-22, where higher values represent more severe depression. This instrument is completed with a structured interview guide by the clinician based on his/her assessment of the patient's symptoms. This structured interview has been validated for use with time frames shorter than one week. In this study, the HAMD6 was used to assess symptoms occurring in the past 24 hours. | A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1, & 3 |
| Measure | Description | Time Frame |
|---|---|---|
| Montgomery-Asberg Depression Rating Scale (MADRS) | The MADRS is a 10-item clinician-rated scale measuring depression severity. Symptoms are rated on a 7-point scale, where 0 = "not present", and 1-6 represent increasing severity. Values 2, 4, and 6 have specific anchoring text (e.g., 2="Difficulties in starting activities." 4="Difficulties in starting simple routine activities which are carried out with effort, 6="Complete lassitude. Unable to do anything without help.") Values 1, 3, and 5 do not have specific text. The possible scale range is 0-60, where higher values represent higher severity. In this study, the MADRS was used to rate symptoms occurring in the past 3 days. |
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Inclusion Criteria:
Exclusion Criteria:
Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study
Female that is pregnant or breastfeeding
Female with a positive pregnancy test at screening or baseline
History during the current MDE of failure to achieve a satisfactory response to >7 treatment courses of a therapeutic dose of an antidepressant therapy of at least 8 weeks duration during the current episode
Total MADRS score of <20 at the screen or baseline visits, or as assessed by the remote, independent MGH CTNI rater and reported to the site
Current diagnosis of a Substance Use Disorder (Abuse or Dependence) with the exception of nicotine dependence, at screening or within 6 months prior to screening
Current Axis I disorder that is the principal focus of treatment and MDD the secondary focus of treatment for the past 6 months or more
History of bipolar disorder, schizophrenia or schizoaffective disorders, or any history of psychotic symptoms in the current or previous depressive episodes
History of eating disorders within five years of screening
Any Axis I or Axis II Disorder, which at screening is clinically predominant to their MDD or has been predominant at any time within 6 months prior to screening
Subject is considered at significant risk for suicidal behavior during the course of their participation in the study
Has failed to respond to electroconvulsive therapy (ECT) during the current depressive episode
Has received vagus nerve stimulation (VNS) at any time prior to screening
Has dementia, delirium, amnestic, or any other cognitive disorder
Has a clinically significant abnormality on the screening physical examination
Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation
Current episode of:
Current history of hypertension, or on antihypertensives for the purpose of lowering blood pressure, who have either had an increase in antihypertensive dose or increase in the number of antihypertensive drugs used to treat hypertension over the last 2 months.
Chronic lung disease excluding asthma.
Lifetime history of surgical procedures involving the brain or meninges, encephalitis, meningitis, degenerative central nervous system disorder, epilepsy, mental retardation, or any other disease/procedure/accident/intervention associated with significant injury to or malfunction of the central nervous system, or a history of significant head trauma within the past 2 years
Presents with any of the following lab abnormalities:
i. Unstable diabetes mellitus defined as glycosylated hemoglobin (HbA1c) >8.5% at screening ii. Admitted to hospital for treatment of diabetes mellitus or diabetes mellitus related illness in the past 12 weeks iii. Not under physician care for diabetes mellitus iv. Has not been on the same dose of oral hypoglycaemic drug(s) and/or diet for the 4 weeks prior to screening. For thiazolidinediones (glitazones) this period should not be less than 8 weeks.
c. Any other clinically significant abnormal laboratory result (as determined after evaluation by study investigator and MGH CTNI medical monitor) at the time of the screening exam.
History of hypothyroidism and has been on a stable dosage of thyroid replacement medication for less than 2 months prior to screening. (Subjects on a stable dosage of thyroid replacement medication for at least 2 months or more prior to screening are eligible for enrollment.)
History of hyperthyroidism which was treated (medically or surgically) less than six months prior to screening
Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation
History of positive screening urine test for drugs of abuse at screening
Patients with exclusionary laboratory values, or requiring treatment with exclusionary concomitant medications
Patients on exclusionary concomitant psychotropic medications, the half-life of which would not allow sufficient time for patients to have been free of the medication post-taper for five half-lives within the maximum screening period (28 days).
Patient who have participated in studies of ketamine or AZD6765 or other NMDA receptor antagonists for depression and received active treatment.
Patients with narrow angle glaucoma
Patients with a lifetime history of PCP/Ketamine drug use
Liver Function Tests higher than 2.5 times upper limit of normal
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| Name | Affiliation | Role |
|---|---|---|
| Maurizio Fava, MD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University | Palo Alto | California | 94304 | United States | ||
| Yale University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 14399272 | Background | HAMILTON M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960 Feb;23(1):56-62. doi: 10.1136/jnnp.23.1.56. No abstract available. | |
| 6080235 | Background | Hamilton M. Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol. 1967 Dec;6(4):278-96. doi: 10.1111/j.2044-8260.1967.tb00530.x. No abstract available. |
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The screening period served as a wash-out period for any prohibited medications that could be discontinued safely. Discontinuation of medications were discussed in consultation with the prescribing clinician.
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| ID | Title | Description |
|---|---|---|
| FG000 | Ketamine 0.1mg | Patients in this arm will receive 0.1 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.1 mg/kg - one single infusion |
| FG001 | Ketamine 0.2mg |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| OTHER |
| University of Texas | OTHER |
| Yale University | OTHER |
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| Ketamine |
| Drug |
Dose of Ketamine will be 0.2 mg/kg - one single infusion |
|
| Ketamine | Drug | Dose of Ketamine will be 0.5 mg/kg - one single infusion |
|
| Ketamine | Drug | Dose of Ketamine will be 1.0 mg/kg - one single infusion |
|
| Placebo Midazolam | Drug | Dose of Midazolam (active placebo) will be 0.045 mg/kg - one single infusion |
|
| A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0 and 3. |
| Clinical Global Impressions-Severity (CGI-S) | The CGI-S is a clinician rated single-item scale: "How depressed is the patient at this time?", rated on a 7-point response scale: 1 = Normal, not at all depressed, 2 = Borderline depressed, 3 = Mildly depressed, 4 = Moderately depressed. 5 = Markedly depressed, 6 = severely depressed, 7 = Among the most severely depressed patients. When rating patients, clinicians were asked to consider the past 24 hours. | A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1 and 3 |
| Clinical Global Impressions-Improvement (CGI-I) Scale | The CGI-I is a clinician rated single-item scale: "Compared to the patient's condition at admission, how much has the patient changed?", rated on a 7-point response scale: 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, and 7 = Very much worse. In this case, "admission" referred to the CGI-S screening assessments performed between Day -28 an -7, one conducted during the screening visit, and a second rating conducted by a remote, independent rater. | A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1 and 3 |
| Symptoms of Depression Questionnaire (SDQ) | The SDQ is a 44-item self-report scale, which aims to measure depression more comprehensively by including the assessment of symptoms in the anxiety-depression spectrum, including symptoms of irritability, anger attacks, and anxiety. Items are rated on an 6-point Likert scale, where participants are asked to rate if a specific symptom (e.g. "How has your mood been over the past 24 hours?") is normal for him or her (score = 2), what is better than normal (score = 1), and what is worse than normal (scores = 3-6). The total scale score is calculated by averaging across the items, resulting in a possible range from 1 to 6. Higher scores indicate greater depression severity. When rating, patients were asked to consider their symptoms during the past 24 hours. | A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1 and 3 |
| Clinical Positive Affect Scale (CPAS) | The CPAS is a 16-item self-report scale to assess the level to which participants experience persistent distress due to feeling that they have not returned to their normal or premorbid state. Items (e.g., "I look forward to things") are rated on a 5-point scale (0=not at all, 1=very much less than normal, 2=much less than normal, 3=slightly less than normal, 4=same as best or normal self). The possible scale range is 0 to 64, with higher scores indicating greater recovery from depression. Patients were asked to rate their experience of the past 24 hours. | A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1 and 3 |
| Snaith-Hamilton Pleasure-Scale (SHAPS) | The SHAPS is a 14-item self-report scale to measure hedonic tone. Items (e.g., "I would enjoy reading a book, magazine, or newspaper.") are rated on a 4-point scale (1=strongly disagree, 2=disagree, 3=agree, 4=strongly agree). Either of the 'disagree' responses scores 1 point, and either of the 'agree' responses scores 0 points, for a total scale range of 0-14. Higher scores indicate greater inability to experience pleasure. Patients were asked to rate their experience of the past 24 hours. | A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1 and 3 |
| Clinician-Administered Dissociative States Scale (CADSS) Scores During Infusion | The CADSS is a 23-item self-report scale for the assessment of dissociative states. It is a reliable, valid self-report instrument. The severity of each dissociative symptom ranges from 0 (not present) to 4 (extreme). The total score is calculated by summing across items, with a total possible range of 0-92. The CADSS was administered right before infusion, and 40, 80 minute and 120 minutes after the start of infusion. The timeframe is "at this moment". | Day 0/baseline at 0, 40, 80, and 120 minutes |
| Number of Participants Reporting Suicidal Ideation/Behavior on the Columbia Suicide Severity Rating Scale (C-SSRS) | The Columbia Suicide Severity Rating Scale (C-SSRS): The C-SSRS is a low-burden measure of the spectrum of suicidal ideation and behavior that was developed in the National Institute of Mental Health Treatment of Adolescent Suicide Attempters Study to assess severity and track suicidal events through any treatment. It is a clinical interview providing a summary of both ideation and behavior that can be administered during any evaluation or risk assessment to identify the level and type of suicidality present. The C-SSRS can also be used during treatment to monitor for clinical worsening or improvement. It contains 5 rating scale questions (yes/no) for suicidal ideation increasing severity and 5 rating scale questions (yes/no) for suicidal behavior of increasing severity. The time frame is for both lifetime and the past six months for the Baseline/Screening scale and since the last visit for the Since Last Visit scale. | Screening Visit and Days 0, 1, 3, 5, 7, 14 and 30 combined |
| Number of Participants With Abnormal and Clinically Significant CBC and Chemistry Labs by Treatment |
Testing was performed by study site laboratories and used institutional normal lab value ranges. | Day 3 and Early Termination Visit (approximately 3 weeks following intervention) |
| New Haven |
| Connecticut |
| 06520 |
| United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Mount Sinai School of Medicine | New York | New York | 10029 | United States |
| University of Texas Southwestern | Dallas | Texas | 75390 | United States |
| Baylor College of Medicine | Houston | Texas | 77030 | United States |
| 444788 | Background | Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979 Apr;134:382-9. doi: 10.1192/bjp.134.4.382. |
| Background | Guy W, editor. ECDEU Assessment Manual for Psychopharmacology. Rockville, MD: US Department of Heath, Education, and Welfare Public Health Service Alcohol, Drug Abuse, and Mental Health Administration; 1976. |
| 22990434 | Background | Nierenberg AA, Bentley KH, Farabaugh AH, Fava M, Deckersbach T. The absence of depressive symptoms is not the presence of wellness: validation of the Clinical Positive Affect Scale. Aust N Z J Psychiatry. 2012 Dec;46(12):1165-72. doi: 10.1177/0004867412459810. Epub 2012 Sep 18. |
| 17606655 | Background | Posner K, Oquendo MA, Gould M, Stanley B, Davies M. Columbia Classification Algorithm of Suicide Assessment (C-CASA): classification of suicidal events in the FDA's pediatric suicidal risk analysis of antidepressants. Am J Psychiatry. 2007 Jul;164(7):1035-43. doi: 10.1176/ajp.2007.164.7.1035. |
| 7551619 | Background | Snaith RP, Hamilton M, Morley S, Humayan A, Hargreaves D, Trigwell P. A scale for the assessment of hedonic tone the Snaith-Hamilton Pleasure Scale. Br J Psychiatry. 1995 Jul;167(1):99-103. doi: 10.1192/bjp.167.1.99. |
| 9479681 | Background | Bremner JD, Krystal JH, Putnam FW, Southwick SM, Marmar C, Charney DS, Mazure CM. Measurement of dissociative states with the Clinician-Administered Dissociative States Scale (CADSS). J Trauma Stress. 1998 Jan;11(1):125-36. doi: 10.1023/A:1024465317902. |
| 36383742 | Derived | Feeney A, Hoeppner BB, Freeman MP, Flynn M, Iosifescu DV, Trivedi MH, Sanacora G, Mathew SJ, DeBattista C, Ionescu DF, Cusin C, Papakostas GI, Jha MK, Fava M. Effect of Concomitant Benzodiazepines on the Antidepressant Effects of Ketamine: Findings From the RAPID Intravenous Ketamine Study. J Clin Psychiatry. 2022 Nov 14;84(1):22m14491. doi: 10.4088/JCP.22m14491. |
| 34090255 | Derived | Feeney A, Hock RS, Freeman MP, Flynn M, Hoeppner B, Iosifescu DV, Trivedi MH, Sanacora G, Mathew SJ, Debattista C, Ionescu DF, Fava M, Papakostas GI. The effect of single administration of intravenous ketamine augmentation on suicidal ideation in treatment-resistant unipolar depression: Results from a randomized double-blind study. Eur Neuropsychopharmacol. 2021 Aug;49:122-132. doi: 10.1016/j.euroneuro.2021.04.024. Epub 2021 Jun 3. |
| 32332464 | Derived | Freeman MP, Hock RS, Papakostas GI, Judge H, Cusin C, Mathew SJ, Sanacora G, Iosifescu DV, DeBattista C, Trivedi MH, Fava M. Body Mass Index as a Moderator of Treatment Response to Ketamine for Major Depressive Disorder. J Clin Psychopharmacol. 2020 May/Jun;40(3):287-292. doi: 10.1097/JCP.0000000000001209. |
| 30283029 | Derived | Fava M, Freeman MP, Flynn M, Judge H, Hoeppner BB, Cusin C, Ionescu DF, Mathew SJ, Chang LC, Iosifescu DV, Murrough J, Debattista C, Schatzberg AF, Trivedi MH, Jha MK, Sanacora G, Wilkinson ST, Papakostas GI. Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD). Mol Psychiatry. 2020 Jul;25(7):1592-1603. doi: 10.1038/s41380-018-0256-5. Epub 2018 Oct 3. |
Patients in this arm will receive 0.2 mg/kg of Ketamine - one single infusion
Ketamine: Dose of Ketamine will be 0.2 mg/kg - one single infusion
| FG002 | Ketamine 0.5mg | Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion |
| FG003 | Ketamine 1.0mg | Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion |
| FG004 | Midazolam (Active Placebo) | Patients in this arm will receive 0.045 mg/kg of midazolam - one single infusion Placebo Midazolam: Dose of Midazolam (active placebo) will be 0.045 mg/kg - one single infusion |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Ketamine 0.1mg | Patients in this arm will receive 0.1 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.1 mg/kg - one single infusion |
| BG001 | Ketamine 0.2mg | Patients in this arm will receive 0.2 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.2 mg/kg - one single infusion |
| BG002 | Ketamine 0.5mg | Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion |
| BG003 | Ketamine 1.0mg | Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion |
| BG004 | Midazolam (Active Placebo) | Patients in this arm will receive 0.045 mg/kg of midazolam - one single infusion Placebo Midazolam: Dose of Midazolam (active placebo) will be 0.045 mg/kg - one single infusion |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| BMI | Mean | Standard Deviation | kg/m^2 |
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| Abnormal and Clinically Significant Labs | Collected at Screening and Day 0 (Day 0 is pre-treatment) CBC, Chemistry (Total bilirubin, AST, ALT, GGT, ALK Phosphatase, Creatinine, BUN/Urea, Glucose, Uric Acid),Hormonal Measures in female subjects: Estradiol, Progesterone, FSH, LH, SHBG, Testosterone; Free testosterone, Hormonal Measures in male subjects: Testosterone, free testosterone, SHBG, DHEA, Progesterone, TSH, Pregnancy Test, Urine Tox Screen | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Hamilton Rating Scale for Depression - 6 Items | The HAMD6 is a 6-item clinician-rated scale, where clinicians rate the presence of depression symptoms (i.e., depressed mood, guilt, work and interests, psychomotor retardation, psychic anxiety, somatic symptoms) on a 5-point scale, where 0 = not present, and 1-4 represent increasingly severe symptoms. One item (i.e., somatic symptoms) is rated on only a 3-point scale, ranging from 0-2. The possible scale range is 0-22, where higher values represent more severe depression. This instrument is completed with a structured interview guide by the clinician based on his/her assessment of the patient's symptoms. This structured interview has been validated for use with time frames shorter than one week. In this study, the HAMD6 was used to assess symptoms occurring in the past 24 hours. | Several subjects dropped out of the study in between Day 0, Day 1 and Day 3. | Posted | Mean | Standard Deviation | units on a scale | A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1, & 3 |
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| Secondary | Montgomery-Asberg Depression Rating Scale (MADRS) | The MADRS is a 10-item clinician-rated scale measuring depression severity. Symptoms are rated on a 7-point scale, where 0 = "not present", and 1-6 represent increasing severity. Values 2, 4, and 6 have specific anchoring text (e.g., 2="Difficulties in starting activities." 4="Difficulties in starting simple routine activities which are carried out with effort, 6="Complete lassitude. Unable to do anything without help.") Values 1, 3, and 5 do not have specific text. The possible scale range is 0-60, where higher values represent higher severity. In this study, the MADRS was used to rate symptoms occurring in the past 3 days. | Several subjects dropped out of the study in between Day 0, Day 1 and Day 3. | Posted | Mean | Standard Deviation | units on a scale | A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0 and 3. |
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| Secondary | Clinical Global Impressions-Severity (CGI-S) | The CGI-S is a clinician rated single-item scale: "How depressed is the patient at this time?", rated on a 7-point response scale: 1 = Normal, not at all depressed, 2 = Borderline depressed, 3 = Mildly depressed, 4 = Moderately depressed. 5 = Markedly depressed, 6 = severely depressed, 7 = Among the most severely depressed patients. When rating patients, clinicians were asked to consider the past 24 hours. | Several subjects dropped out of the study in between Day 0, Day 1 and Day 3. | Posted | Mean | Standard Deviation | units on a scale | A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1 and 3 |
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| Secondary | Clinical Global Impressions-Improvement (CGI-I) Scale | The CGI-I is a clinician rated single-item scale: "Compared to the patient's condition at admission, how much has the patient changed?", rated on a 7-point response scale: 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, and 7 = Very much worse. In this case, "admission" referred to the CGI-S screening assessments performed between Day -28 an -7, one conducted during the screening visit, and a second rating conducted by a remote, independent rater. | Several subjects dropped out of the study in between Day 0, Day 1 and Day 3. | Posted | Mean | Standard Deviation | units on a scale | A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1 and 3 |
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| Secondary | Symptoms of Depression Questionnaire (SDQ) | The SDQ is a 44-item self-report scale, which aims to measure depression more comprehensively by including the assessment of symptoms in the anxiety-depression spectrum, including symptoms of irritability, anger attacks, and anxiety. Items are rated on an 6-point Likert scale, where participants are asked to rate if a specific symptom (e.g. "How has your mood been over the past 24 hours?") is normal for him or her (score = 2), what is better than normal (score = 1), and what is worse than normal (scores = 3-6). The total scale score is calculated by averaging across the items, resulting in a possible range from 1 to 6. Higher scores indicate greater depression severity. When rating, patients were asked to consider their symptoms during the past 24 hours. | Several subjects dropped out of the study in between Day 0, Day 1 and Day 3. | Posted | Mean | Standard Deviation | units on a scale | A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1 and 3 |
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| Secondary | Clinical Positive Affect Scale (CPAS) | The CPAS is a 16-item self-report scale to assess the level to which participants experience persistent distress due to feeling that they have not returned to their normal or premorbid state. Items (e.g., "I look forward to things") are rated on a 5-point scale (0=not at all, 1=very much less than normal, 2=much less than normal, 3=slightly less than normal, 4=same as best or normal self). The possible scale range is 0 to 64, with higher scores indicating greater recovery from depression. Patients were asked to rate their experience of the past 24 hours. | Several subjects dropped out of the study in between Day 0, Day 1 and Day 3. | Posted | Mean | Standard Deviation | units on a scale | A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1 and 3 |
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| Secondary | Snaith-Hamilton Pleasure-Scale (SHAPS) | The SHAPS is a 14-item self-report scale to measure hedonic tone. Items (e.g., "I would enjoy reading a book, magazine, or newspaper.") are rated on a 4-point scale (1=strongly disagree, 2=disagree, 3=agree, 4=strongly agree). Either of the 'disagree' responses scores 1 point, and either of the 'agree' responses scores 0 points, for a total scale range of 0-14. Higher scores indicate greater inability to experience pleasure. Patients were asked to rate their experience of the past 24 hours. | Several subjects dropped out of the study in between Day 0, Day 1 and Day 3. | Posted | Mean | Standard Deviation | units on a scale | A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1 and 3 |
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| Secondary | Clinician-Administered Dissociative States Scale (CADSS) Scores During Infusion | The CADSS is a 23-item self-report scale for the assessment of dissociative states. It is a reliable, valid self-report instrument. The severity of each dissociative symptom ranges from 0 (not present) to 4 (extreme). The total score is calculated by summing across items, with a total possible range of 0-92. The CADSS was administered right before infusion, and 40, 80 minute and 120 minutes after the start of infusion. The timeframe is "at this moment". | Posted | Mean | Standard Deviation | units on a scale | Day 0/baseline at 0, 40, 80, and 120 minutes |
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| Secondary | Number of Participants Reporting Suicidal Ideation/Behavior on the Columbia Suicide Severity Rating Scale (C-SSRS) | The Columbia Suicide Severity Rating Scale (C-SSRS): The C-SSRS is a low-burden measure of the spectrum of suicidal ideation and behavior that was developed in the National Institute of Mental Health Treatment of Adolescent Suicide Attempters Study to assess severity and track suicidal events through any treatment. It is a clinical interview providing a summary of both ideation and behavior that can be administered during any evaluation or risk assessment to identify the level and type of suicidality present. The C-SSRS can also be used during treatment to monitor for clinical worsening or improvement. It contains 5 rating scale questions (yes/no) for suicidal ideation increasing severity and 5 rating scale questions (yes/no) for suicidal behavior of increasing severity. The time frame is for both lifetime and the past six months for the Baseline/Screening scale and since the last visit for the Since Last Visit scale. | Posted | Count of Participants | Participants | Screening Visit and Days 0, 1, 3, 5, 7, 14 and 30 combined |
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| Secondary | Number of Participants With Abnormal and Clinically Significant CBC and Chemistry Labs by Treatment |
Testing was performed by study site laboratories and used institutional normal lab value ranges. | Posted | Count of Participants | Participants | Day 3 and Early Termination Visit (approximately 3 weeks following intervention) |
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Number of patients with adverse events post infusion (treatment) up to 30 days.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ketamine 0.1mg | Patients in this arm will receive 0.1 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.1 mg/kg - one single infusion | 0 | 18 | 0 | 18 | 17 | 18 |
| EG001 | Ketamine 0.2mg | Patients in this arm will receive 0.2 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.2 mg/kg - one single infusion | 0 | 20 | 1 | 20 | 18 | 20 |
| EG002 | Ketamine 0.5mg | Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion | 0 | 22 | 0 | 22 | 14 | 22 |
| EG003 | Ketamine 1.0mg | Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion | 0 | 20 | 0 | 20 | 17 | 20 |
| EG004 | Midazolam (Active Placebo) | Patients in this arm will receive 0.045 mg/kg of midazolam - one single infusion Placebo Midazolam: Dose of Midazolam (active placebo) will be 0.045 mg/kg - one single infusion | 0 | 19 | 0 | 19 | 10 | 19 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Suicide Attempt | Psychiatric disorders | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Depression | Psychiatric disorders | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | Systematic Assessment |
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| Abnormal Dreams | Psychiatric disorders | Systematic Assessment |
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| Back Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Blood Pressure Increase | Cardiac disorders | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Insomnia | Psychiatric disorders | Systematic Assessment |
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| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Pain In Extremity | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Poor Quality Sleep | Psychiatric disorders | Systematic Assessment |
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| Suicidal Ideation | Psychiatric disorders | Systematic Assessment |
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| Tachycardia | Cardiac disorders | Systematic Assessment |
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| Tooth Abscess | Infections and infestations | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Asthenia | Nervous system disorders | Systematic Assessment |
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| Blood Testosterone | Reproductive system and breast disorders | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Dermatitis | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Dermatitis Contact | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Dissociation | Psychiatric disorders | Systematic Assessment |
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| Dizziness | General disorders | Systematic Assessment |
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| Exposure to Toxic Agent | Injury, poisoning and procedural complications | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | Systematic Assessment |
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| Flushing | Vascular disorders | Systematic Assessment |
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| Gastroenteritis Viral | Infections and infestations | Systematic Assessment |
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| Hepatic Enzyme Increased | Hepatobiliary disorders | Systematic Assessment |
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| Hot Flush | Vascular disorders | Systematic Assessment |
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| Hypertension | Cardiac disorders | Systematic Assessment |
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| Increased Appetite | Gastrointestinal disorders | Systematic Assessment |
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| Initial Insomnia | Psychiatric disorders | Systematic Assessment |
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| Intentional Self-Injury | Psychiatric disorders | Systematic Assessment |
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| Loss of Consciousness | Nervous system disorders | Systematic Assessment |
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| Malaise | Psychiatric disorders | Systematic Assessment |
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| Overdose | Psychiatric disorders | Systematic Assessment |
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| Presyncope | General disorders | Systematic Assessment |
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| Respiratory Tract Infection | Infections and infestations | Systematic Assessment |
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| Self Injurious Behavior | Psychiatric disorders | Systematic Assessment |
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| Sinusitis | Infections and infestations | Systematic Assessment |
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| Upper Respiratory Tract Infection | Infections and infestations | Systematic Assessment |
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| Vertigo | Vascular disorders | Systematic Assessment |
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| Viral Upper Respiratory Tract Infection | Infections and infestations | Systematic Assessment |
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| White Blood Cell Count Decreased | Blood and lymphatic system disorders | Systematic Assessment |
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Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Maurizio Fava, MD | Massachusetts General Hospital | 617-724-2513 | MFAVA@mgh.harvard.edu |
| ID | Term |
|---|---|
| D061218 | Depressive Disorder, Treatment-Resistant |
| D003863 | Depression |
| D003865 | Depressive Disorder, Major |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
Not provided
Not provided
| ID | Term |
|---|---|
| D007649 | Ketamine |
| ID | Term |
|---|---|
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
Not provided
Not provided
| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Chemistry |
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| Hormonal Measures (testosterone, SHBG, Free T) |
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| Hormonal Measures (DHEA) |
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| Hormonal Measures (remaining tests) |
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| Pregnancy Test |
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| Urine Toxicology Screen |
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| Day 1 |
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| Day 3 |
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| Superiority |
| Ketamine 0.2mg/kg vs. midazolam at Day 1: As estimated by the repeated measures fixed effects model with DAY (0, 1, 3), GROUP (5 groups as specified above), and the DAY*GROUP interaction effect. Because there were eight pairwise comparisons of interest (see Analysis 1-8), we used Holm's method to protect family-wise error rate in the presence of multiple testing. | Mixed Models Analysis | 0.79 | Holm's method was applied to the model-produced differences of least squares for the eight a priori identified contrasts of interest, that is, the difference between each ketamine group vs. placebo at Days 1 and 3. | Mean Difference (Final Values) | -1.13 | 2-Sided | 95 | -3.75 | 1.49 | Superiority |
| Ketamine 0.5mg/kg vs. midazolam at Day 1: As estimated by the repeated measures fixed effects model with DAY (0, 1, 3), GROUP (5 groups as specified above), and the DAY*GROUP interaction effect. Because there were eight pairwise comparisons of interest (see Analysis 1-8), we used Holm's method to protect family-wise error rate in the presence of multiple testing. | Mixed Models Analysis | <0.01 | Holm's method was applied to the model-produced differences of least squares for the eight a priori identified contrasts of interest, that is, the difference between each ketamine group vs. placebo at Days 1 and 3. | Mean Difference (Final Values) | -4.79 | 2-Sided | 95 | -7.35 | -2.24 | Superiority |
| Ketamine 1.0mg/kg vs. midazolam at Day 1: As estimated by the repeated measures fixed effects model with DAY (0, 1, 3), GROUP (5 groups as specified above), and the DAY*GROUP interaction effect. Because there were eight pairwise comparisons of interest (see Analysis 1-8), we used Holm's method to protect family-wise error rate in the presence of multiple testing. | Mixed Models Analysis | 0.04 | Mean Difference (Final Values) | -3.76 | 2-Sided | 95 | -6.37 | -1.15 | Superiority |
| Ketamine 0.1mg/kg vs. midazolam at Day 3: As estimated by the repeated measures fixed effects model with DAY (0, 1, 3), GROUP (5 groups as specified above), and the DAY*GROUP interaction effect. Because there were eight pairwise comparisons of interest (see Analysis 1-8), we used Holm's method to protect family-wise error rate in the presence of multiple testing. | Mixed Models Analysis | 0.72 | Holm's method was applied to the model-produced differences of least squares for the eight a priori identified contrasts of interest, that is, the difference between each ketamine group vs. placebo at Days 1 and 3. | Mean Difference (Final Values) | -2.04 | 2-Sided | 95 | -5.04 | 0.95 | Superiority |
| Ketamine 0.2mg/kg vs. midazolam at Day 3: As estimated by the repeated measures fixed effects model with DAY (0, 1, 3), GROUP (5 groups as specified above), and the DAY*GROUP interaction effect. Because there were eight pairwise comparisons of interest (see Analysis 1-8), we used Holm's method to protect family-wise error rate in the presence of multiple testing. | Mixed Models Analysis | 0.80 | Holm's method was applied to the model-produced differences of least squares for the eight a priori identified contrasts of interest, that is, the difference between each ketamine group vs. placebo at Days 1 and 3. | Mean Difference (Final Values) | -0.36 | 2-Sided | 95 | -3.18 | 2.46 | Superiority |
| Ketamine 0.5mg/kg vs. midazolam at Day 3: As estimated by the repeated measures fixed effects model with DAY (0, 1, 3), GROUP (5 groups as specified above), and the DAY*GROUP interaction effect. Because there were eight pairwise comparisons of interest (see Analysis 1-8), we used Holm's method to protect family-wise error rate in the presence of multiple testing. | Mixed Models Analysis | 0.14 | Holm's method was applied to the model-produced differences of least squares for the eight a priori identified contrasts of interest, that is, the difference between each ketamine group vs. placebo at Days 1 and 3. | Mean Difference (Final Values) | -3.12 | 2-Sided | 95 | -5.97 | -0.44 | Superiority |
| Ketamine 1.0mg/kg vs. midazolam at Day 3: As estimated by the repeated measures fixed effects model with DAY (0, 1, 3), GROUP (5 groups as specified above), and the DAY*GROUP interaction effect. Because there were eight pairwise comparisons of interest (see Analysis 1-8), we used Holm's method to protect family-wise error rate in the presence of multiple testing. | Mixed Models Analysis | 0.72 | Holm's method was applied to the model-produced differences of least squares for the eight a priori identified contrasts of interest, that is, the difference between each ketamine group vs. placebo at Days 1 and 3. | Mean Difference (Final Values) | -1.84 | 2-Sided | 95 | -4.65 | 0.96 | Superiority |
| OG002 | Ketamine 0.5mg | Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion |
| OG003 | Ketamine 1.0mg | Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion |
| OG004 | Midazolam 0.045mg | Patients in this arm will receive 0.045 mg/kg of Midazolam (active placebo) - one single infusion |
|
|
|
Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion
Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion
| OG003 | Ketamine 1.0mg | Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion |
| OG004 | Midazolam 0.045mg | Patients in this arm will receive 0.045 mg/kg of Midazolam (active placebo) - one single infusion |
|
|
|
| Ketamine 0.5mg |
Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion |
| OG003 | Ketamine 1.0mg | Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion |
| OG004 | Midazolam 0.045mg | Patients in this arm will receive 0.045 mg/kg of Midazolam (active placebo) - one single infusion |
|
|
|
| OG002 | Ketamine 0.5mg | Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion |
| OG003 | Ketamine 1.0mg | Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion |
| OG004 | Midazolam 0.045mg | Patients in this arm will receive 0.045 mg/kg of Midazolam (active placebo) - one single infusion |
|
|
|
| Ketamine 0.5mg |
Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion |
| OG003 | Ketamine 1.0mg | Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion |
| OG004 | Midazolam 0.045mg | Patients in this arm will receive 0.045 mg/kg of Midazolam (active placebo) - one single infusion |
|
|
|
Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion |
| OG003 | Ketamine 1.0mg | Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion |
| OG004 | Midazolam 0.045mg | Patients in this arm will receive 0.045 mg/kg of Midazolam (active placebo) - one single infusion |
|
|
|
| OG003 |
| Ketamine 1.0mg |
Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion |
| OG004 | Midazolam 0.045mg | Patients in this arm will receive 0.045 mg/kg of Midazolam (active placebo) - one single infusion |
|
|
| OG002 | Ketamine 0.5mg | Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion |
| OG003 | Ketamine 1.0mg | Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion |
| OG004 | Midazolam 0.045mg | Patients in this arm will receive 0.045 mg/kg of Midazolam (active placebo) - one single infusion |
|
|
| OG004 | Midazolam 0.045mg | Patients in this arm will receive 0.045 mg/kg of Midazolam (active placebo) - one single infusion |
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