Ketamine hydrochloride for Acute respiratory failure requiring unplanned invasive mechanical ventilation

Inclusion criteria

• {"criterion_text":"- •\tPatients over 18 years of age\n- •\tSigned informed consent or inclusion under the emergency provisions of the law (ArticleL1122 -1-3 of the PHC / modified by Order n°2016-800 of June 16 2016 - art. 2)\n- •\tNeed for unplanned invasive mechanical ventilation\n- •\tNeed for continuous intravenous sedative agents (propofol, midazolam or dexmedetomidine) for more than 6 hours.\n- •\tAffiliation to a social security system (excluding “Aide Médicale d’Etat” [AME])"}

Exclusion criteria

• {"criterion_text":"- •\tRefusal to participate in the study\n- •\tPersons deprived of liberty\n- •\tPersons on a protective judicial measure\n- •\tSevere arterial hypertension ( mean arterial pressure>130 mmHg) despite treatment\n- •\tHypersensitivity to the active substances or any of the excipients\n- •\tKnown contraindications to ketamine according to the SmPC (Severe heart failure, history of stroke, severe uncontrolled hypertension, severe aneurysmal disease, pheochromocytoma)\n- •\tAcute brain injuries (i.e. acute stroke, traumatic brain injury, cardiac arrest, brain infections) or conditions (status epilepticus or coma with suspected/confirmed intracranial hypertension at admission requiring deep sedation)\n- •\tStatus asthmaticus\n- •\tCurrent liver failure with Model for End-Stage Liver Disease (MELD) > 30\n- •\tInitiation of mechanical ventilation > 48 hour\n- •\tExpected lifespan < 24 hours\n- •\tPatients already receiving a continuous infusion of ketamine\n- •\tCurrently participating in another interventional clinical trial investigating sedation or protocols using Ketamine or another drug which may interact with Ketamine or which may have an impact on the evaluation of the trial's judgement criteria.\n- •\tPositive highly sensitive pregnancy test\n- •\tPsychosis"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint will be the number of days patients are alive and spent at home at 60 days after drug or placebo initiation. This endpoint will be collected by an independent research assistant, blinded to randomization groups and not involved in data monitoring onsite.","definition_or_measurement_approach":"Number of days alive and spent at home at 60 days after initiation; collected by an independent research assistant blinded to randomization and not involved in onsite data monitoring."}

Secondary endpoints

• {"endpoint_text":"- The number of days alive free of encephalopathy (coma or delirium measured on the CAM-ICU) during 14 days after randomization","definition_or_measurement_approach":"Days alive without encephalopathy (coma or delirium) during first 14 days post-randomization, measured by CAM-ICU."}
• {"endpoint_text":"- The number of days spent alive without invasive mechanical ventilation (ventilation-free days) at 60 days;","definition_or_measurement_approach":"Ventilation-free days at day 60 post-randomization."}
• {"endpoint_text":"- The number of days spent alive without infusion norepinephrine or inotropes infusion during ICU stay (vasopressors-free days) at 60 days;","definition_or_measurement_approach":"Vasopressor-free days during ICU stay up to day 60."}
• {"endpoint_text":"- Mortality, defined by the prevalence of all-cause deaths at 60 and 90 days;","definition_or_measurement_approach":"All-cause mortality prevalence measured at day 60 and day 90."}
• {"endpoint_text":"- Toxicité rénale, définie par la proportion de patients atteignant un stade KDIGO ≥2 à 60 jours ;","definition_or_measurement_approach":"Renal toxicity defined as proportion of patients reaching KDIGO stage ≥2 at 60 days."}
• {"endpoint_text":"- Liver toxicity, defined by the highest bilirubin and phosphatase alkaline level during the first 60 days;","definition_or_measurement_approach":"Liver toxicity defined by highest bilirubin and alkaline phosphatase levels during first 60 days."}
• {"endpoint_text":"- Quantification of opioid and sedative consumption during the treatment period, in each arm during the first 14 days.","definition_or_measurement_approach":"Quantification of opioid and sedative consumption in each arm during first 14 days (exploratory)."}
• {"endpoint_text":"- Mean daily pain (BPS) and sedation (RASS) scores, in each arm during the first 14 days","definition_or_measurement_approach":"Daily mean pain (BPS) and sedation (RASS) scores measured during first 14 days."}
• {"endpoint_text":"- Cumulative incidence of hallucination events during 14 days after randomization","definition_or_measurement_approach":"Cumulative incidence of hallucination events within 14 days post-randomization."}
• {"endpoint_text":"- Presence of anxiety and depression, defined by a score ≥11 on the anxiety and depression components of the Hospital Anxiety and Depression scale, respectively at 90 days; (tertiary outcome)","definition_or_measurement_approach":"Anxiety and depression assessed at day 90 using HADS; score ≥11 indicates presence."}
• {"endpoint_text":"- Acute posttraumatic stressdisorder (PTSD)-related (measured on the ICU memory tool) at 90 days. (tertiary outcome)","definition_or_measurement_approach":"PTSD-related outcomes measured at day 90 using the ICU Memory Tool."}

France

Earliest CTIS Part Ii Submission Date

07-04-2026

Latest Decision Or Authorization Date

05-05-2026

Processing Time Days

28

Number Of Sites

19

Number Of Participants

640

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France