Deze pagina is automatisch vertaald en de nauwkeurigheid van de vertaling kan niet worden gegarandeerd. Raadpleeg de Engelse versie voor een brontekst.

KetAmine and Recovery After Mechanical VentilAtion ( KARMA ) (KARMA)

13 mei 2026 bijgewerkt door: Assistance Publique - Hôpitaux de Paris

Intensive Care Treatment With Adjuvant KetAmine and Recovery After Mechanical ventilAtion: a Multicenter Doubleblind Randomized Controlled Trial.

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.

Studie Overzicht

Toestand

Nog niet aan het werven

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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).

Studietype

Ingrijpend

Inschrijving (Geschat)

640

Fase

  • Fase 3

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Contact Back-up

Studie Locaties

  • Frankrijk
      • Paris, Frankrijk, 75018
        • Department of Intensive Care Medicine, APHP.Nord, hôpital Bichat Claude Bernard,
        • Contact:

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Beschrijving

Inclusion Criteria :

  1. Patients over 18 years of age
  2. Signed 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)
  3. Need for unplanned invasive mechanical ventilation
  4. Need for continuous intravenous sedative agents (propofol, midazolam or dexmedetomidine) for more than 6 hours.
  5. Affiliation to a social security system (excluding "Aide Médicale d'Etat" [AME])

Exclusion Criteria

  1. Refusal to participate in the study
  2. Acute 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)
  3. Psychosis
  4. Status asthmaticus
  5. Current liver failure with Model for End-Stage Liver Disease (MELD) > 30
  6. Initiation of mechanical ventilation > 48 hours
  7. Expected lifespan < 24 hours
  8. Patients already receiving a continuous infusion of ketamine
  9. Currently 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.
  10. Positive highly sensitive pregnancy test
  11. Persons deprived of liberty
  12. Persons on a protective judicial measure
  13. Breastfeeding
  14. Severe arterial hypertension (mean arterial pressure>130 mmHg) despite treatment
  15. Hypersensitivity to the active substances or any of the excipients
  16. Known contraindications to ketamine according to the SmPC (Severe heart failure, history of stroke, severe uncontrolled hypertension, severe aneurysmal disease, pheochromocytoma)

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Dubbele

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Actieve vergelijker: Intervention group

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
Geneesmiddel: Intervention Group
Ketamine ® is supplied in 250 mg/5 ml vials containing sterile solution for dilution in sodium chlorure 0.9% for infusions.
Placebo-vergelijker: Control 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
Geneesmiddel: Placebo
Placebo : NaCl 0.9% (vials)

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Number of days patients are alive and spent at home
Tijdsspanne: At 60 days after ketamine initiation
This endpoint will be collected by an independent research assistant, blinded to randomization groups, , and not involved in data monitoring onsite.
At 60 days after ketamine initiation

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Number of days alive free of encephalopathy
Tijdsspanne: During 14 days after randomization
Number of days spent alive without coma or delirium measured on the CAM-ICU
During 14 days after randomization
number of days spent alive without invasive mechanical ventilation
Tijdsspanne: At day 60
ventilation-free days
At day 60
Number of days spent alive without infusion norepinephrine infusion during ICU stay
Tijdsspanne: At day 60
Vasopressors-free days
At day 60
Mortality
Tijdsspanne: At Day 60 et Day 90
Defined by the prevalence of all-cause deaths
At Day 60 et Day 90
Renal toxicity,
Tijdsspanne: At Day 60
Defined by the proportion of patients with a KDIGO stage ≥2
At Day 60
Liver toxicity
Tijdsspanne: At Day 60
Defined by the highest bilirubin and phosphatase alkaline level
At Day 60
Quantification of opioid and sedative consumption
Tijdsspanne: Within the 14 days after randomization
During the treatment period, in each arms during the first 14 days
Within the 14 days after randomization
Mean daily pain (BPS)
Tijdsspanne: During the first 14 days after randomisation
Mean daily Behavioral Pain Scale (BPS) score assessed during the first 14 days.
During the first 14 days after randomisation
Cumulative incidence of hallucination events
Tijdsspanne: During 14 days after randomization
During 14 days after randomization
Mean daily sedation score (RASS)
Tijdsspanne: During the first 14 days after randomisation
Mean daily Richmond Agitation-Sedation Scale (RASS) score assessed during the first 14 days.
During the first 14 days after randomisation

Andere uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
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;
Tijdsspanne: At Day 90

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.
At Day 90
Acute posttraumatic stressdisorder (PTSD)-related
Tijdsspanne: . At Day 90
Measured on the ICU memory tool. This outcomes will be reported in an ancillary analysis separated from the main report of the trial
. At Day 90

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Assistance Publique - Hôpitaux de Paris

Onderzoekers

  • Hoofdonderzoeker: Romain Prof SONNEVILLE, MD-PHD, APHP

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Geschat)

19 oktober 2026

Primaire voltooiing (Geschat)

19 december 2029

Studie voltooiing (Geschat)

19 januari 2030

Studieregistratiedata

Eerst ingediend

5 mei 2026

Eerst ingediend dat voldeed aan de QC-criteria

13 mei 2026

Eerst geplaatst (Werkelijk)

15 mei 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

15 mei 2026

Laatste update ingediend die voldeed aan QC-criteria

13 mei 2026

Laatst geverifieerd

1 mei 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • APHP240938

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

Abonneren