KARMA - INtenSive care TreAtmeNT with adjuvant KetAmine and Recovery after Mechanical ventilAtion: a multicenter doubleblind randomized controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Decision date (initial)

2026-04-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

PHRC 2024

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective will be to assess recovery from critical illness in patients requiring unplanned invasive mechanical ventilation in the ICU.

Secondary objectives 11

1. To assess duration of encephalopathy (coma or delirium) within the first 14 days after randomization.
2. To assess the number of days patients are alive and free from invasive mechanical ventilation within 60 days following randomization
3. To the number of days patients are alive and free from vasopressors or inotropes within 60 days following randomization
4. To assess mortality at days 60 and 90.
5. To assess renal toxicity within 60 days following randomization
6. To assess liver toxicity within 60 days following randomization
7. To measure opioid and sedative consumption in each arm as an exploratory outcome during the first 14 days .
8. To measure pain and sedation status in each arm as an exploratory outcome during the first 14 days
9. To measure hallucination events in each arm as an exploratory outcome during the first 14 days
10. To assess neuropsychological sequelae (i.e, anxiety, depression) at day 90; (tertiary outcome)
11. To assess post-traumatic stress disorder (PTSD) at day 90 (tertiary outcome)

Conditions and MedDRA coding

Adult patients admitted to the ICU and receiving unplanned invasive mechanical ventilation

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

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 15

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 11

1. The number of days alive free of encephalopathy (coma or delirium measured on the CAM-ICU) during 14 days after randomization
2. The number of days spent alive without invasive mechanical ventilation (ventilation-free days) at 60 days;
3. The number of days spent alive without infusion norepinephrine or inotropes infusion during ICU stay (vasopressors-free days) at 60 days;
4. Mortality, defined by the prevalence of all-cause deaths at 60 and 90 days;
5. Toxicité rénale, définie par la proportion de patients atteignant un stade KDIGO ≥2 à 60 jours ;
6. Liver toxicity, defined by the highest bilirubin and phosphatase alkaline level during the first 60 days;
7. Quantification of opioid and sedative consumption during the treatment period, in each arm during the first 14 days.
8. Mean daily pain (BPS) and sedation (RASS) scores, in each arm during the first 14 days
9. Cumulative incidence of hallucination events during 14 days after randomization
10. 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)
11. Acute posttraumatic stressdisorder (PTSD)-related (measured on the ICU memory tool) at 90 days. (tertiary outcome)

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Investigateur

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Investigateur

Locations

1 EU/EEA country · 19 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications