Ketamine maintenance treatment for depression: A multicenter open-label randomized controlled trial (PreKET)

Status Authorised, recruitment pending · 1 EU/EEA countries · 11 sites · Protocol PreKET

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)

Status Authorised, recruitment pending

Participants planned 230

Countries 1

Sites 11

Major Depression Disorder (MDD)

To examine the long-term efficacy of maintenance therapy with IV ketamine following induction treatment of treatment-resistant depression (TRD).

Key facts

Sponsor: Ostfold Hospital Trust
Participant type: Patients
Age range: 18-64 years, 65+ years
Gender: Male and Female
Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02], Psychiatry and Psychology [F] - Mental Disorders [F03], Psychiatry and Psychology [F] - Psychological Phenomena [F02]
Decision date (initial): 2025-11-05
Transition trial: No
Low-intervention: No
Rare-disease indication: No
Vulnerable population: No
Funding sources: Ostfold Hospital Trust

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Dose response, Safety

To examine the long-term efficacy of maintenance therapy with IV ketamine following induction treatment of treatment-resistant depression (TRD).

Secondary objectives 3

To examine the durability of the antidepressant effect of IV ketamine after the maintenance treatment
To assess the safety of IV ketamine treatment of TRD
To assess efficacy of dose- and duration-dependent acute therapy with IV ketamine in TRD

Conditions and MedDRA coding

Major Depression Disorder (MDD)

Version	Level	Code	Term	System organ class
21.1	PT	10057840	Major depression	100000004873
26.0	LLT	10088521	Treatment resistant depression	100000004848

Study design 3 periods

#	Title	Allocation	Blinding	Arms
1	Screening Over a period of a week, the potential subjects will visit the study site for tests to verify eligibility.	Not Applicable	None
2	Dose finding The subject qualified for the study will receive 2 ketamine treatments each week over a period of 3-5 weeks to optimize the dose.	Not Applicable	None
3	Maintenance phase After the dose finding period, the ones obtaining response or remission, will enter this phase.	Randomised Controlled	None	Ketamine 8 treatments: Monthly ketamine treatments for 8 months, followed by site visits for follow-up purposes for 6 months; a total of 14 months. Ketamine 4 treatments: Monthly ketamine treatments for 4 months, followed by site visits for follow-up purposes for 10 months; a total of 14 months. TAU: Site visits for follow-up purposes for 14 months after the initial dose finding period.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

● Are fluent in spoken and written Norwegian.
● Able to provide informed consent to participate in the current study. This may include involuntarily hospitalized patients
● Male or female adults aged 18 years or older
● Meet DSM-5 criteria for MDD or bipolar-2 disorder as assessed by the MINI version 7.0.2
● Have a current MDE of at least moderate severity defined by a Montgomery-Åsberg Depression Rating Scale (MADRS) score of ≥ 20
● Meet criteria for treatment-resistant depression, defined by previous treatment for depression included a minimum of two evidence-based treatments (psychopharmacology, psychotherapy, ECT/TMS) without adequate response, in accordance with Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of unipolar or bipolar depression
● Women of childbearing potential (WOCBP) as defined in Section 10.4.1 must have a negative pregnancy test at study entry and prior to maintenance ketamine infusion and must agree to use adequate birth control through the last ketamine infusion.
• Only highly effective contraception methods are permitted in this trial. See Section 10.6.2 Contraception guidelines for a list of these methods.

Exclusion criteria 28

● Women who intend to become pregnant or are breast-feeding
● Ongoing or previous manic episodes
● History of any psychotic or bipolar type 1 disorder as assessed by the Mini International Neuropsychiatric Interview (MINI v. 7.0.2)
● History of severe personality disorder, severe dissociative disorder, severe obsessive-compulsive disorder, autism-spectrum disorder, or other psyciatric comorbidities, assessed through MINI and/or medical history, that may interfere with the interpretation of the study results or pose a health risk to the participant per investigator’s judgement
● Current eating disorder with active purging as assessed by MINI
● Current or past severe substance/alcohol use disorder (according to DSM-5 criteria) or substance/alcohol use that, in the investigator’s judgment, may compromise participant safety, study integrity, or compliance with study procedures
● Cardiovascular conditions: Heart failure (NYHA class III or IV), recent stroke (< 1 year from enrollment), recent myocardial infarction (< 1 year from enrollment), uncontrolled hypertension (>160/100 mm Hg) or recent clinically significant arrhythmia (< 1 year from enrolment)
● Liver failure (Child-Pugh Class C) or impairment of liver function as assessed by medical history, clinical examination and laboratory results at screening (i.e. INR > 1,2 or bilirubin > 30 μmol/L)
● Kidney failure (creatinine clearance < 30 mL/min by Cockcroft-Gault)
● Chronic respiratory failure (requiring LTOT and/or GOLD 3 (severe) or higher)
● Obstructive or central sleep apnoea requiring treatment with oxygen, CPAP/BiPAP
● Pregnant women as assessed by blood HCG tests
● Glaucoma or globe injury
● Previous anaphylactic reaction to ketamine
● Uncontrolled hypo- or hyperthyroidism
● Current or suspected increased intracranial pressure
● Acute intermittent porphyria
● Any other severe medical or neurological condition that, in the investigator’s judgement, may interfere with the interpretation of the study results or pose a health risk to the participant.
● Any use of medication deemed by the trial medical professionals to pose a risk when combined with ketamine or likely to interfere with the study results, and that the participant is unwilling or unable to discontinue before enrolment
● Electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) are not permitted within four weeks prior to enrollment or during the trial.
● Ketamine treatment within 6 months preceding enrollment
● Not able to provide informed consent to participate in clinical research
● BMI under 16 or over 35 or body weight over 150 kg
● Outpatients with acute suicide risk as assessed by clinician’s examination
● Hospitalized patients with acute suicide risk, unless enrollment doesn’t interfere with clinical security procedures per investigator’s judgement
● Ongoing psychotic symptoms unless exclusively explained by the current depressive episode
● Ongoing hypomanic episode
• Known hypersensitivity to any ingredients of ketamine

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

• Time-to-relapse after induction phase assessed by clinician rated MADRS between all 3 treatment arms
• Time-to-relapse after the last ketamine infusion assessed by clinician rated MADRS between all three treatment arms

Secondary endpoints 1

• Assess frequency, severity and duration of ARs/SARs through clinical interview, observation, SCI-2 SF, DLCQ and PreKET symptom checklist, patient chart review, spontaneously reported adverse events from signing the ICF to Final visit.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Ketamine Hydrochloride

SUB02830MIG · Substance

Active substance: Ketamine Hydrochloride
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INFUSION
Max daily dose: 150 mg milligram(s)
Max total dose: 2700 mg milligram(s)
Max treatment duration: 10 Week(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ostfold Hospital Trust

Sponsor organisation: Ostfold Hospital Trust
Address: P. O. Box 16
City: Fredrikstad
Postcode: 1603
Country: Norway

Scientific contact point

Organisation: Ostfold Hospital Trust
Contact name: Mark Berthold-Losleben

Public contact point

Organisation: Ostfold Hospital Trust
Contact name: Pål Øyvind Ulleberg Dåstøl

Locations

1 EU/EEA country · 11 investigational sites

By country

Country	MS status	Planned subjects	Sites
Norway	Authorised, recruitment pending	230	11
Rest of world	—	0	—

Investigational sites

Norway

11 sites · Authorised, recruitment pending

Sykehuset Innlandet HF

Div Psykisk helsevern - Hamar, P. O. Box 104, 2381, Brumunddal

St. Olavs Hospital HF

.., P. O. Box 3250, Torgarden, Trondheim

Universitetssykehuset Nord-Norge HF

.., P. O. Box 100, 9038, Tromsoe

Sykehuset I Vestfold HF

.., Halfdan Wilhelmsens Alle 17, 3116, Toensberg

Akershus University Hospital

.., Sykehusveien 25, 1474, Loerenskog

Sorlandet Sykehus HF

..., Egsveien 100, 4615, Kristiansand S

Helse Bergen HF

Kronstad DPS, P. O. Box 1400, 5021, Bergen

Helse Stavanger HF

.., P. O. Box 8100, 4068, Stavanger

Sykehuset Ostfold HF

KlinBeForsk, Kalnesveien 300, 1714, Graalum