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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06278779




Registration number
NCT06278779
Ethics application status
Date submitted
20/01/2024
Date registered
26/02/2024
Date last updated
4/06/2024

Titles & IDs
Public title
Comparative Effectiveness Study of Two Forms of Ketamine for Treatment-resistant Depression
Scientific title
Comparative Effectiveness Study of Two Forms of Ketamine for Treatment-Resistant Depression: a Randomised, Rater-blinded Trial
Secondary ID [1] 0 0
X23-0311
Universal Trial Number (UTN)
Trial acronym
TREK
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Treatment Resistant Depression 0 0
Condition category
Condition code
Mental Health 0 0 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Esketamine group
Treatment: Drugs - Racemic ketamine

Active Comparator: Esketamine group - Dosing of esketamine intranasal spray will be guided by the Spravato® Product Information. This involves a starting dosage of 28 or 56 mg, with dose adjustment up to 84 mg as required to optimise response. Dose adjustments will be based on effectiveness and tolerability to the previous dose. The recommended treatment protocol is twice per week for 4 weeks, then weekly in weeks 5-8, then option of weekly-fortnightly "maintenance" treatment for responders. After week 8, patients may continue treatment as guided by the ketamine clinic psychiatrist.

Active Comparator: Racemic ketamine - Treatment administration will follow standard clinical practice in the recruiting clinic, with a recommendation to follow an evidence-based and established dose-optimising approach, given by injection, twice per week for 4 weeks, then the frequency of further treatments (week 5 - month 6) will be based on the clinical judgement of the ketamine clinic psychiatrist.
Dosing will be adjusted by the ketamine clinic psychiatrist, based on clinical response, safety and tolerability. The psychiatrist will review the patient before each treatment, over the first 4 weeks, to judge the dose level required.
Typically, dosing will begin at the standard dose of 0.5 mg/kg and adjusted using an ascending dose titration schedule if the patient has not shown clinical response and if side effects are adequately tolerated.
.


Treatment: Drugs: Esketamine group
The recommended dosing for Spravato is:
Weeks 1-4:
Starting Day 1 dose:
< 65 years: 56 mg
= 65 years: 28 mg
Subsequent doses:
28 mg (= 65 years), 56 mg or 84 mg twice weekly
Weeks 5-8:
28 mg (= 65 years), 56 mg or 84 mg once weekly
From Week 9:
28 mg (= 65 years), 56 mg or 84 mg every 2 weeks or once weekly

Treatment: Drugs: Racemic ketamine
Typically, dosing will begin at the standard dose of 0.5 mg/kg and adjusted as needed using an ascending dose titration schedule:
0.5 mg/kg
0.6 mg/kg
0.75 mg/kg
0.9 mg/kg
Further increments by 0.1-0.2 mg/kg, up to max 1.5 mg/kg
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Montgomery-Asberg Depression Rating Scale (MADRS)
Timepoint [1] 0 0
From week 0 to week 4.
Secondary outcome [1] 0 0
Montgomery-Asberg Depression Rating Scale (MADRS) score
Timepoint [1] 0 0
At week 8 and month 6
Secondary outcome [2] 0 0
Response - Montgomery-Asberg Depression Rating Scale (MADRS)
Timepoint [2] 0 0
Weeks 4, 8 and month 6
Secondary outcome [3] 0 0
Remission - Montgomery-Asberg Depression Rating Scale (MADRS)
Timepoint [3] 0 0
Weeks 4, 8 and month 6
Secondary outcome [4] 0 0
DASS-21
Timepoint [4] 0 0
Performed weekly from baseline to week 8 inclusive and at 6 month visit.
Secondary outcome [5] 0 0
Clinical Global Impression-Improvement (CGI-I)
Timepoint [5] 0 0
Performed weekly from week 1 to week 4 inclusive, then at week 8 and at 6 month visits.
Secondary outcome [6] 0 0
Clinical Global Impression-Severity (CGI-S)
Timepoint [6] 0 0
Performed weekly from baseline to week 4 inclusive, then at week 8 and at 6 month visits.
Secondary outcome [7] 0 0
Columbia Suicide Severity Rating Scale (C-SSRS)
Timepoint [7] 0 0
Performed weekly from baseline to week 4 inclusive, then at week 8 and at 6 month visits.
Secondary outcome [8] 0 0
Speed of response - Clinical Global Impression-Improvement (CGI-I)
Timepoint [8] 0 0
Performed weekly from week 1 to week 4 inclusive, then at week 8 and at 6 month visits.
Secondary outcome [9] 0 0
Psychotomimetic symptoms
Timepoint [9] 0 0
Through study completion at each treatment visit, up to 6 months
Secondary outcome [10] 0 0
Suicide attempts or gestures
Timepoint [10] 0 0
During 6-month study period
Secondary outcome [11] 0 0
Number of Participants with urinary symptoms, as assessed using the Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS)
Timepoint [11] 0 0
Performed at baseline, week 4, week 8 and at 6 month visit.
Secondary outcome [12] 0 0
Cognitive Failure Questionnaire scores (CFQ)
Timepoint [12] 0 0
Performed at baseline, week 4, week 8 and at 6 month visit.
Secondary outcome [13] 0 0
Ketamine liking/craving score
Timepoint [13] 0 0
Performed at baseline, week 4, week 8 and at 6 month visit.
Secondary outcome [14] 0 0
Number of Participants with urinary symptoms, as assessed using the Ketamine Side Effect Tool (KSET)
Timepoint [14] 0 0
Through study completion at each treatment visit, up to 6 months
Secondary outcome [15] 0 0
Acceptability Questionnaire
Timepoint [15] 0 0
Performed at week 4, week 8 and at 6 month visit.
Secondary outcome [16] 0 0
End of Treatment questionnaire
Timepoint [16] 0 0
Used at end of the treatment period(s) over the course of the study.
Secondary outcome [17] 0 0
Recovering Quality of Life Questionnaire (REQOL-10)
Timepoint [17] 0 0
Over 6 month study period
Secondary outcome [18] 0 0
WHO Disability Assessment Scale (WHODAS-12)
Timepoint [18] 0 0
Over 6 month study period
Secondary outcome [19] 0 0
Patient Health Questionnaire-9 (PHQ-9)
Timepoint [19] 0 0
Over 6 month study period
Secondary outcome [20] 0 0
Assessment of Quality of Life Questionnaire (AQoL-8D)
Timepoint [20] 0 0
Over 6 month study period
Secondary outcome [21] 0 0
Resource Use Questionnaire (RUQ)
Timepoint [21] 0 0
Over 6 month study period
Secondary outcome [22] 0 0
Treatment Preference
Timepoint [22] 0 0
Assessed once, prior to randomization
Secondary outcome [23] 0 0
Stanford Expectations of Treatment Scale (SETS)
Timepoint [23] 0 0
Assessed once, after randomization and before first treatment

Eligibility
Key inclusion criteria
- Adult with treatment-resistant depression (TRD: not responded adequately to at least
two different antidepressants of adequate dose and duration) who has a current
depressive episode (DSM 5)

- Assessed and attested by clinic psychiatrist as appropriate to receive either racemic
ketamine or Spravato® ketamine treatment for TRD

- Aged =18 years

- Written informed consent for research study obtained
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Not able to give informed consent

- Any physical or mental condition which, in the opinion of the investigator, could
interfere with study participation including outcome assessments

- Patients who require an interpreter/translator for the clinic consent process, due to
the infeasibility of obtaining an interpreter for research assessments, including
self-rated scales

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/06/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/04/2027
Actual
Sample size
Target
162
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Black Dog Institute - Randwick
Recruitment hospital [3] 0 0
Ramsay Clinic Northside - St Leonards
Recruitment hospital [4] 0 0
Ramsay Clinic Lakeside - Warners Bay
Recruitment hospital [5] 0 0
Gold Coast University Hospital - Southport
Recruitment hospital [6] 0 0
Ramsay Clinic Albert Road - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2065 - St Leonards
Recruitment postcode(s) [4] 0 0
2282 - Warners Bay
Recruitment postcode(s) [5] 0 0
4215 - Southport
Recruitment postcode(s) [6] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
The George Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
The University of New South Wales
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The goal of this study is to compare the effectiveness of two formulations of ketamine -
Spravato® and racemic ketamine - in people with treatment-resistant depression (TRD). The
main questions it aims to answer are:

- How the two formulations compare in terms of their effectiveness in treating TRD.

- How the two formulations compare in their acceptability to patients, safety, effects on
patient quality of life and function, and cost effectiveness.

Participants will be randomised to receive either Spravato® or racemic ketamine treatment and
asked to complete some questionnaires to assess the effects on mood, treatment acceptability,
side effects, quality of life and function, and health economic outcomes.
Trial website
https://clinicaltrials.gov/ct2/show/NCT06278779
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Colleen Loo
Address 0 0
The University of New South Wales
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Simone Jacoby
Address 0 0
Country 0 0
Phone 0 0
80524300
Fax 0 0
Email 0 0
sjacoby@georgeinstitute.org.au
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06278779