Trial Outcomes & Findings for Efficacy of Repeated Ketamine Infusions for Treatment-resistant Depression (NCT NCT02360280)

Last Updated: 2024-04-25

Results Overview

Average difference in the Montgomery-Asberg Depression Rating Scale (MADRS) score change between groups. The MADRS has 10-items which are based on mood symptoms over the past 7 days. Each items is scored 0 (normal) to 6 (severe depression) with overall score ranges from 0 (normal) to 60 (severe depression).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

62 participants

Primary outcome timeframe

13 days

Results posted on

2024-04-25

Participant Flow

Recruitment from April 2015 through October 2018

Four subjects were enrolled but not assigned to treatment. They voluntarily decided to decline participation for logistical issues.

Participant milestones

Participant milestones
Measure	Six Ketamine Infusions Six infusions of 0.5 mg/Kg of ketamine hydrochloride solution over 2 weeks. ketamine: sedative	Single Ketamine Infusion Preceded by 5 Midazolam Infusions Single infusion of 0.5 mg/Kg of ketamine hydrochloride solution preceded by midazolam 0.045 mg/kg over 2 weeks. ketamine: sedative midazolam: sedative
Overall Study STARTED	28	30
Overall Study COMPLETED	25	29
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Six Ketamine Infusions Six infusions of 0.5 mg/Kg of ketamine hydrochloride solution over 2 weeks. ketamine: sedative	Single Ketamine Infusion Preceded by 5 Midazolam Infusions Single infusion of 0.5 mg/Kg of ketamine hydrochloride solution preceded by midazolam 0.045 mg/kg over 2 weeks. ketamine: sedative midazolam: sedative
Overall Study Withdrawal by Subject	2	0
Overall Study Adverse Event	0	1
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

Efficacy of Repeated Ketamine Infusions for Treatment-resistant Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Six Ketamine Infusions n=25 Participants Six infusions of 0.5 mg/Kg of ketamine hydrochloride solution over 2 weeks. ketamine: sedative	Single Ketamine Infusion Preceded by 5 Midazolam Infusions n=29 Participants Single infusion of 0.5 mg/Kg of ketamine hydrochloride solution preceded by midazolam 0.045 mg/kg over 2 weeks. ketamine: sedative midazolam: sedative	Total n=54 Participants Total of all reporting groups
Age, Continuous	54.4 years STANDARD_DEVIATION 13.8 • n=5 Participants	51.2 years STANDARD_DEVIATION 12.5 • n=7 Participants	52.7 years STANDARD_DEVIATION 13.1 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	24 Participants n=7 Participants	46 Participants n=5 Participants
Race/Ethnicity, Customized White	21 participants n=5 Participants	25 participants n=7 Participants	46 participants n=5 Participants
Race/Ethnicity, Customized Black/African American	3 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment United States	25 Participants n=5 Participants	29 Participants n=7 Participants	54 Participants n=5 Participants
MADRS	34.88 units on a scale STANDARD_DEVIATION 7.79 • n=5 Participants	33.82 units on a scale STANDARD_DEVIATION 5.11 • n=7 Participants	34.32 units on a scale STANDARD_DEVIATION 6.41 • n=5 Participants
IDS-C	36.8 units on a scale STANDARD_DEVIATION 3.9 • n=5 Participants	39.8 units on a scale STANDARD_DEVIATION 7.3 • n=7 Participants	38.4 units on a scale STANDARD_DEVIATION 6.1 • n=5 Participants
BAI	12.32 units on a scale STANDARD_DEVIATION 13.62 • n=5 Participants	10.57 units on a scale STANDARD_DEVIATION 6.88 • n=7 Participants	11.31 units on a scale STANDARD_DEVIATION 10.42 • n=5 Participants
CGI	5.32 units on a scale STANDARD_DEVIATION 0.56 • n=5 Participants	5.14 units on a scale STANDARD_DEVIATION 0.64 • n=7 Participants	5.22 units on a scale STANDARD_DEVIATION 0.60 • n=5 Participants
NRS	3.16 units on a scale STANDARD_DEVIATION 2.49 • n=5 Participants	3.37 units on a scale STANDARD_DEVIATION 2.09 • n=7 Participants	3.27 units on a scale STANDARD_DEVIATION 2.26 • n=5 Participants

PRIMARY outcome

Timeframe: 13 days

Outcome measures

Outcome measures
Measure	Six Ketamine Infusions n=25 Participants Six infusions of 0.5 mg/Kg of ketamine hydrochloride solution over 2 weeks. ketamine: sedative	Single Ketamine Infusion Preceded by 5 Midazolam Infusions n=29 Participants Single infusion of 0.5 mg/Kg of ketamine hydrochloride solution preceded by midazolam 0.045 mg/kg over 2 weeks. ketamine: sedative midazolam: sedative
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score After 12 Days of Treatment	21.0 units on a scale Interval 17.2 to 24.8	17.2 units on a scale Interval 13.2 to 21.2

SECONDARY outcome

Timeframe: 13 days

Comparing the number of subjects that achieve response between groups as defined above.

Outcome measures

Outcome measures
Measure	Six Ketamine Infusions n=25 Participants Six infusions of 0.5 mg/Kg of ketamine hydrochloride solution over 2 weeks. ketamine: sedative	Single Ketamine Infusion Preceded by 5 Midazolam Infusions n=29 Participants Single infusion of 0.5 mg/Kg of ketamine hydrochloride solution preceded by midazolam 0.045 mg/kg over 2 weeks. ketamine: sedative midazolam: sedative
Antidepressant Response Defined as >50% Decrease in MADRS Baseline Score	19 Participants	20 Participants

SECONDARY outcome

Timeframe: 13 days

Comparing the number of subjects that achieve remission between groups as defined above

Outcome measures

Outcome measures
Measure	Six Ketamine Infusions n=25 Participants Six infusions of 0.5 mg/Kg of ketamine hydrochloride solution over 2 weeks. ketamine: sedative	Single Ketamine Infusion Preceded by 5 Midazolam Infusions n=29 Participants Single infusion of 0.5 mg/Kg of ketamine hydrochloride solution preceded by midazolam 0.045 mg/kg over 2 weeks. ketamine: sedative midazolam: sedative
Remission Defined as MADRS Score Equal or Less Than 9	12 Participants	11 Participants

SECONDARY outcome

Timeframe: 6 months

Population: The overall number of participants in each intervention corresponds to the total number of subjects that achieve response at the end of six infusions.

The length of time from post-infusion response until relapse (defined as \>50% of MADRS baseline score) assessed for up to 6 months.

Outcome measures

Outcome measures
Measure	Six Ketamine Infusions n=19 Participants Six infusions of 0.5 mg/Kg of ketamine hydrochloride solution over 2 weeks. ketamine: sedative	Single Ketamine Infusion Preceded by 5 Midazolam Infusions n=20 Participants Single infusion of 0.5 mg/Kg of ketamine hydrochloride solution preceded by midazolam 0.045 mg/kg over 2 weeks. ketamine: sedative midazolam: sedative
Time From Post-infusion Response to Occurrence of Relapse Defined as <50% of Baseline MADRS Score	6.00 weeks Interval 0.0 to 16.81	2.00 weeks Interval 0.0 to 4.92

Adverse Events

Six Ketamine Infusions

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Single Ketamine Infusion Preceded by 5 Midazolam Infusions

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Six Ketamine Infusions n=25 participants at risk Six infusions of 0.5 mg/Kg of ketamine hydrochloride solution over 2 weeks. ketamine: sedative	Single Ketamine Infusion Preceded by 5 Midazolam Infusions n=29 participants at risk Single infusion of 0.5 mg/Kg of ketamine hydrochloride solution preceded by midazolam 0.045 mg/kg over 2 weeks. ketamine: sedative midazolam: sedative
Nervous system disorders Recurrent headaches	4.0% 1/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	3.4% 1/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.

Other adverse events

Additional Information

Paulo R. Shiroma

Minneapolis VA Medical Center

Phone: 612-467-2264

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Six Ketamine Infusions n=25 participants at risk Six infusions of 0.5 mg/Kg of ketamine hydrochloride solution over 2 weeks. ketamine: sedative	Single Ketamine Infusion Preceded by 5 Midazolam Infusions n=29 participants at risk Single infusion of 0.5 mg/Kg of ketamine hydrochloride solution preceded by midazolam 0.045 mg/kg over 2 weeks. ketamine: sedative midazolam: sedative
Cardiac disorders Increased in blood pressure	24.0% 6/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	17.2% 5/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.
Gastrointestinal disorders Nausea	20.0% 5/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	6.9% 2/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.
Respiratory, thoracic and mediastinal disorders Respiratory distress	4.0% 1/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	3.4% 1/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.
Nervous system disorders Dizziness	4.0% 1/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	10.3% 3/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.
Nervous system disorders Tremors	4.0% 1/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	0.00% 0/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.
Gastrointestinal disorders Constipation	4.0% 1/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	3.4% 1/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.
Gastrointestinal disorders Dry mouth	0.00% 0/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	3.4% 1/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.
Skin and subcutaneous tissue disorders Increased perspiration	0.00% 0/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	3.4% 1/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.
Skin and subcutaneous tissue disorders Itching	4.0% 1/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	3.4% 1/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.
Eye disorders Blurred vision	0.00% 0/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	6.9% 2/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.
Ear and labyrinth disorders Ringing in ears	0.00% 0/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	3.4% 1/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.
Renal and urinary disorders Frequent urination	0.00% 0/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	3.4% 1/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.
Psychiatric disorders Insomnia	16.0% 4/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	10.3% 3/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.
Nervous system disorders Sleeping too much	16.0% 4/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	10.3% 3/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.
Psychiatric disorders Restlessness	12.0% 3/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	0.00% 0/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.
Psychiatric disorders Anxiety	20.0% 5/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	24.1% 7/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.
Psychiatric disorders Decreased energy	28.0% 7/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	17.2% 5/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.
Nervous system disorders Poor concentration	20.0% 5/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	6.9% 2/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.
Psychiatric disorders Fatigue	24.0% 6/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	13.8% 4/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.
General disorders General malaise	28.0% 7/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	6.9% 2/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.
Reproductive system and breast disorders Loss of sexual desire	16.0% 4/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	10.3% 3/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.
Reproductive system and breast disorders Trouble achieving orgasm	4.0% 1/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	6.9% 2/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.
Reproductive system and breast disorders Trouble with erections	0.00% 0/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	6.9% 2/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.
Nervous system disorders Headaches	24.0% 6/25 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.	13.8% 4/29 • The time frame of data collection was 3 years and 8 months (from April 2015 through December 2018). Each participant was assessed for up to 28 weeks.