A Phase 3 interventional study of Intervention Group and Placebo in Critical Illness, sponsored by Assistance Publique - Hôpitaux de Paris. Not yet recruiting at 1 site in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-15.
Sponsored by Assistance Publique - Hôpitaux de Paris · Phase 3, Interventional, and Treatment
Invasive mechanical ventilation of critically ill patients in the intensive care unit (ICU) is associated with significant morbidity and mortality, as well as a severe prognosis in survivors, in terms of functional, psychological, and cognitive sequelae. During the initial phase, invasive mechanical ventilation aims to promote oxygenation and reduce respiratory effort, with most patients receiving continuous intravenous sedation comprising gamma-aminobutyric acid (GABA) agonists (propofol, midazolam), and opioids. This continuous intravenous sedation is associated with complications, particularly hemodynamic issues (e.g., hypotension, vasopressor dependency), and neurological concerns (e.g., coma, delayed awakening, withdrawal syndrome upon discontinuation of sedation) during the acute phase and is linked to prolonged mechanical ventilation and long-term neurocognitive sequelae.
The use of ketamine as an alternative sedative agent in ICU has garnered considerable attention in recent years. Ketamine has a rapid onset of action and a short duration of effect, potentially beneficial bronchodilatory effects, and minimal impact on hemodynamics or respiratory drive. It also provides effective analgesia. Due to its action on N-methyl-D-aspartate (NMDA) glutamatergic receptors, its mechanism of action differs from other commonly used agents such as propofol and benzodiazepines. Furthermore, emerging research suggests that ketamine may have anti-inflammatory/immunomodulatory and neuroprotective properties that could be advantageous in critically ill patients.
Recent observational studies utilizing low-dose ketamine have suggested an improvement in neurological complications in ICU (e.g., coma, delirium) while other authors have raised concerns about potential renal and hepatic toxicity associated with high doses of ketamine used for sedation. Despite its increasing use, there is currently a lack of high-quality data on the efficacy and safety of ketamine use for sedation in critically ill patients.
In this trial, we hypothesise that, critically ill patients requiring unplanned invasive mechanical ventilation, adjunctive treatment with low dose of ketamine will translate into better outcomes, with higher numbers of days alive outside of the hospital.
The study is a multicenter, randomised, double-blinded placebo-controlled superiority trial involving adult patients requiring unplanned mechanical ventilation, and sedation for more than 6 hours in the ICU. Patients will be randomised within 48 hours following initiation of mechanical ventilation adhering to a 1:1 allocation of ketamine or placebo.
Patients will be randomized to receive either intravenous ketamine or placebo as an adjunctive sedative agent during ICU stay for a maximum duration of 14 days.
Follow-up visits will be performed at day 3, day 14, ICU discharge, day 60, and day 90 after randomization.
The primary endpoint, "days alive and at home," will be assessed at day 60. The end of the research visit is the day 90 follow-up visit. If the patient has been discharged from the hospital, the day-90 visit will consist of telephone contact with the patient by a centralized research assistant and he also will complete the scales at D90.
Data collected by phone consist in Vital status, scales's results and Retrieval of Adverse Events if the patient has been discharged home or with the medical team of the healthcare structure if the patient has been discharged to another structure.
Phase III study Prospective, multicenter, superiority, double-blind, randomized controlled study with two arms (1:1).
The study includes a screening/baseline visit (V0), followed by daily assessments during the intervention period (V1 to V4), and post-discharge (V5) follow-up visits at Day 60 (V6) and Day 90 (V7).
At screening and baseline (within 48 hours prior to Day 1), eligibility is confirmed, and informed consent is obtained when possible. In cases where prior consent cannot be obtained, deferred consent procedures are applied in accordance with French legislation. Baseline data include medical history, comorbidities, concomitant treatments, clinical examination, and pregnancy testing when applicable.
Randomization is performed at Day 1 (V1). From Day 1 to Day 14 (V4), patients will be receive either intravenous ketamine or placebo as an adjunctive sedative agent during ICU stay for a maximum duration of 14 days.
Until ICU discharge (V5), patients undergo daily assessments including clinical examination, vital status, organ dysfunction (Sequential Organ Failure Assessment [SOFA] score), At Day 14 (V4), opioid and sedative consumption during the treatment period will be quantified.
At Day 60 (V6), ventilator-free days and vasopressor-free days will be assessed.
Duration of delirium and coma are assessed using the RASS/CAM-ICU, at V 4, during the first 14 days following randomization.
Biological monitoring includes daily measurement of serum creatinine and liver function parameters (ASAT, ALAT, gamma-GT, and bilirubin) to evaluate potential renal and hepatic toxicity. Adverse events are collected throughout the ICU stay, and assessed at Day 60 (V6) At ICU discharge (V5), a clinical evaluation and morbidity/mortality assessment are performed if the patient is still hospitalized.
The primary endpoint-the number of days alive and at home-is assessed at Day 60. Secondary outcomes, including mortality (all-cause deaths), are assessed at both Day 60 (V6) and Day 90(V7).
1,780 studies on the registry are indexed under Critical Illness; 442 are open to participants now.
This study's planned enrollment of 640 is above the median of 90 across 926 interventional studies indexed under Critical Illness.
Browse Critical Illness studies →Assistance Publique - Hôpitaux de Paris is the lead sponsor of 3,592 studies on the registry; 1,033 are open to participants now.
Compared within Critical Illness, the registry's first condition term, which may not be this study's main condition. Counted across the registry records on this site, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ketamine will be started at a dose of 0.2 mg/kg/hour for 4 hours and then adjusted as necessary (+/-0.1 mg/kg/hour every 4 hours) from 0 to 0.6 mg/kg/hour to maintain a targeted RASS of -1 to 0, in addition to standard per local sedation and pain protocols. Duration of treatment: 14 days in maximum
Drug: Intervention Group
Intravenous placebo will be started at a dose of 0.2 mg/kg/hour for 4 hours and adjusted as necessary (+/-0.1 mg/kg/hour every 4 hours) from 0 to 0.6 mg/kg/hour to maintain a targeted RASS of -1 to 0, in addition to standard sedation per local protocol. Duration of treatment : 14 days in maximum
Drug: Placebo
Ketamine ® is supplied in 250 mg/5 ml vials containing sterile solution for dilution in sodium chlorure 0.9% for infusions.
Placebo : NaCl 0.9% (vials)
Number of days patients are alive and spent at home
This endpoint will be collected by an independent research assistant, blinded to randomization groups, , and not involved in data monitoring onsite.
Time frame: At 60 days after ketamine initiation
Number of days alive free of encephalopathy
Number of days spent alive without coma or delirium measured on the CAM-ICU
Time frame: During 14 days after randomization
number of days spent alive without invasive mechanical ventilation
ventilation-free days
Time frame: At day 60
Number of days spent alive without infusion norepinephrine infusion during ICU stay
Vasopressors-free days
Time frame: At day 60
Mortality
Defined by the prevalence of all-cause deaths
Time frame: At Day 60 et Day 90
Renal toxicity,
Defined by the proportion of patients with a KDIGO stage ≥2
Time frame: At Day 60
Liver toxicity
Defined by the highest bilirubin and phosphatase alkaline level
Time frame: At Day 60
Quantification of opioid and sedative consumption
During the treatment period, in each arms during the first 14 days
Time frame: Within the 14 days after randomization
Mean daily pain (BPS)
Mean daily Behavioral Pain Scale (BPS) score assessed during the first 14 days.
Time frame: During the first 14 days after randomisation
Cumulative incidence of hallucination events
Time frame: During 14 days after randomization
Mean daily sedation score (RASS)
Mean daily Richmond Agitation-Sedation Scale (RASS) score assessed during the first 14 days.
Time frame: During the first 14 days after randomisation
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;
Defined by a score ≥11 on the anxiety and depression components of the Hospital Anxiety and Depression scale, respectively . This outcome will be reported in an ancillary analysis separated from the main report of the trial.
Time frame: At Day 90
Acute posttraumatic stressdisorder (PTSD)-related
Measured on the ICU memory tool. This outcomes will be reported in an ancillary analysis separated from the main report of the trial
Time frame: . At Day 90
Start is estimated for Oct 2026; primary completion for Dec 2029, 38 months later.
Of 32 non-industry phase 3 interventional studies under Critical Illness, half reached primary completion within 33 months of starting (the median), counting those still running; a quarter within 20 and three quarters within 59. This study's planned 38 months is above that.
Counting every sponsor, half of 33 studies reached it within 33 months; a quarter within 20 and three quarters within 59.
Critical Illness covers many different conditions, not one, so the studies compared here vary widely. Read these figures as a rough guide.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in May 2026. You cannot join it, but the record below documents what was studied.
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