KETAMINE for Major depressive disorder with current severe major depressive episode

Inclusion criteria

• {"criterion_text":"- Current MDE in the context of Major Depressive Disorder (DSM-5 criteria), hospitalized (open care) for this episode, with a minimum HDRS score of 24 and in the context of an indication for the introduction of venlafaxine treatment.\n- Patient aged between 18 and 65\n- Signed free and informed consent\n- Membership of a social security scheme\n- For women of childbearing age, effective contraception throughout study participation"}

Exclusion criteria

• {"criterion_text":"- Criteria relating to associated pathologies entailing particular risks: pharmaco-resistant MDE (failure of at least two properly conducted treatments with two different antidepressant treatment classes), MDE with psychotic features, psychotic disorder, bipolar disorder, current (<1 month) substance use disorder (excluding tobacco\n- Participating in other interventional research involving the human body or within the exclusion period following previous research involving the human body, if applicable\n- Social insurance\n- Liver impairment (AST and/or ALT > 3 ULN, PAL and/or GGT and/or bilirubin > 2 ULN)\n- Severe renal insufficiency (GFR <30ml/min with Cockcroft's formula)\n- Contraindication to ketamine : Hypersensitivity to active substance or excipients, comatose state, central nervous system (CNS) depression, Parkinson's disease, Lewy body dementia, progressive supranuclear palsy, known prolongation of the QTc interval (>450ms for men and >470ms for women) or congenital long QT syndrome, recent acute myocardial infarction, uncompensated heart failure, history of ventricular arrhythmias or torsades de pointes, uncorrected hypokalemia (K+ < 3. 5 mmol/l), epilepsy, uncontrolled hypertension, porphyria.\n- Contraindication to venlafaxine (hypersensitivity to venlafaxine or excipients, unstable hypertension, no indication for venlafaxine treatment in clinician's opinion due to ineffectiveness or tolerability of previous venlafaxine treatment).\n- Current or previous treatment with venlafaxine or ketamine in the month prior to study inclusion\n- Need to maintain another antidepressant, MAOI, Millepertuis or benzodiazepines (cyamemazine is permitted)\n- Pregnant or breast-feeding patients (women of childbearing potential must have a negative urine or blood test for human chorionic gonadotropin prior to trial entry). Planned pregnancy within three months of enrolment\n- Adult under guardianship, curatorship, or safeguard of justice"}

Primary endpoints

• {"endpoint_text":"- Total score change of the Hamilton Depression Rating Scale (HDRS 17 items: scale items are rated from 0 to 2 or from 0 to 4 and the score ranges from 0 to 52) after 7 days of treatment","definition_or_measurement_approach":"Change in total HDRS-17 score from baseline to day 7; HDRS-17 items rated 0-2 or 0-4 with total score range 0-52."}

Secondary endpoints

• {"endpoint_text":"- 1 et 4) Efficacy: assessed by 5 complementary criteria a)\tmain criteria : Total score change of the Hamilton Depression Rating Scale (HDRS 17) b)\tresponse rate : ≥50% HDRS total score improvement c)\tremission : (HDRS 17 items ≤ 7) d)\tBeck Depression Inventory (BDI) change e)\tClinical Global Impression rating scale (CGI)","definition_or_measurement_approach":"Efficacy assessed using five measures: HDRS-17 change, response rate (≥50% improvement in HDRS total), remission (HDRS-17 ≤7), change in Beck Depression Inventory (BDI), and Clinical Global Impression (CGI)."}
• {"endpoint_text":"- 2) hospital stay length ( the number of days spent in hospital, including re-hospitalization, during the fallow up 42 days). The end of the hospital stay is decided by the clinician blinded to treatment.","definition_or_measurement_approach":"Number of days hospitalized (including re-hospitalizations) during 42-day follow-up; discharge decision by clinician blinded to treatment."}
• {"endpoint_text":"- 3) Total scores change on the Columbia Suicide Risk Scale (C-SSRS)","definition_or_measurement_approach":"Change in total C-SSRS score from baseline to assessment timepoints."}
• {"endpoint_text":"- 5) The safety assessed with Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. The occurrence of adverse effects in the ketamine and placebo groups will be assessed by monitoring during the infusion of treatment or placebo and up to 40 minutes afterwards blood pressure, heart rate, respiratory rate, nausea/vomiting, dissociation, headache.","definition_or_measurement_approach":"Safety graded per CTCAE v5.0; specific monitoring of vitals and adverse events during infusion and up to 40 minutes post-infusion (blood pressure, heart rate, respiratory rate, nausea/vomiting, dissociation, headache)."}
• {"endpoint_text":"- 6) cumulative consumption in mg of cyamemazine over the entire study period","definition_or_measurement_approach":"Total cumulative dose (mg) of cyamemazine consumed over study period."}
• {"endpoint_text":"- 7) biomarkers predictive or associated with the efficacy of ketamine on add on to venlafaxine","definition_or_measurement_approach":"Identification/measurement of biomarkers predictive or associated with response to venlafaxine+ketamine (methods not specified in dataset)."}

France

Earliest CTIS Part Ii Submission Date

19-04-2024

Latest Decision Or Authorization Date

30-03-2026

Processing Time Days

710

Number Of Sites

4

Number Of Participants

60

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"DGOS ET ANR","duties_or_roles":"Source of monetary support","organisation_type":""}