ESKetamine Low-dose vs Ketamine Low-dose for Severe Acute Pain in Emergency Units, Comparison of PsychodyslEptic Effects

NCT06853041 | Completed Phase 4

• 1 other identifier: 24-PP-09
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

Almost 30% of painful patients in emergency departments (ED) describe their pain as severe (i.e. a Verbal Numerical Rating Score VNRS ≥ 6 on a scale ranging from 0 to 10). The management of such severe pain needs to be rapid and safe, and for this purpose intravenous (IV) morphine titration is still the gold-standard. However, morphine titration takes up considerable caregiver time, as patients need to be monitored and treated progressively with small quantities of morphine every 5 minutes until analgesia. This is sometimes difficult to reconcile with a saturating flow of patients, and overcrowding in ED is proven to significantly delay time-to-analgesia, and even lead to deleterious under-treatment. Finally, the opioid crisis is a major concern, explaining why strategies are being advocated to develop other ways of managing severe acute pain in the ED and to limit the use of opioids. Recent studies show that ketamine administered in small IV doses ("low-dose" ketamine LDK: 0.2 to 0.3 mg/kg) possesses potent analgesic activity as well as interesting anti-hyperalgesic and anti-allodynic properties. Compared with morphine, LDK does not induce respiratory depression, but can sometimes induce disturbing psychodysleptic effects. These may include a sensation of unreality, fatigue, anxiety, dizziness or hallucinations. According to studies, 30-80% of LDK-treated patients experience psychodysleptic effects. However, two recent studies suggest that slow IV injections of LDK (over 10 minutes) may improve patient tolerance, although these slow infusions do not totally reduce this discomfort. Pharmacologically, ketamine is a racemic mixture of 2 isomers: esketamine S(+), which is dextrorotatory, and arketamine R(-), which is levorotatory. In recent years, a new formulation containing only esketamine has been made available to hospitals in some northern European countries, and more recently in France. Esketamine appears to have twice the analgesic efficacy of racemic ketamine, and studies on healthy volunteers or in peri-operative settings suggest that it is also better tolerated psychologically than ketamine. For the moment, however, scientific data are lacking, and no comparative trial has yet been conducted in the ED setting. The investigators plan to conduct in their ED a prospective, single-center, randomized, double-blind study aiming to compare the tolerance and efficacy of esketamine versus racemic LDK in patients presenting with severe acute pain (VNRS ≥ 6/10).

Conditions

Acute Pain

Outcome Measures

Primary Outcomes (1)

• Proportion of patients experiencing at least one psychodysleptic effect of the SERSDA (Side Effects Rating Scale for Dissociate Anesthetics) scale.

  The primary endpoint will be the proportion of patients experiencing at least one psychodysleptic effect, in the control group (ketamine IV 0.3 mg/kg) and in the active group (esketamine IV 0.15 mg/kg). Using the SERSDA (Side Effects Rating Scale for Dissociate Anesthetics) scale, the most widely used in studies, which comprises 9 items: fatigue, headache, dizziness, feeling of unreality, generalized feeling of discomfort, hearing changes, vision changes, mood change, hallucination.

  The time of initiation of the ketamine or esketamine infusion defines the minute 0 time point of the study. The presence of any of these 9 SERSDA items will be assessed by patients every 5 minutes from minute 0 to minute 0 + 60 minutes.

Secondary Outcomes (5)

• Intensity of the psychodysleptic effects described by patients.

  The time of initiation of the ketamine or esketamine infusion defines the minute 0 time point of the study. The intensity of the psychodysleptic effects will be assessed by patients every 5 minutes from minute 0 to minute 0 + 60 minutes.

• Analgesic efficacy of the 2 molecules (ketamine or esketamine)

  The time of initiation of the ketamine or esketamine infusion defines the minute 0 time point of the study. The intensity of the psychodysleptic effects will be assessed by patients every 5 minutes from minute 0 to minute 0 + 60 minutes.

• Any other hemodynamic and respiratory adverse event

  The time of initiation of the ketamine or esketamine infusion defines the minute 0 time point of the study. The intensity of the psychodysleptic effects will be assessed by patients every 5 minutes from minute 0 to minute 0 + 60 minutes.

• Any other hemodynamic and respiratory adverse event

  The time of initiation of the ketamine or esketamine infusion defines the minute 0 time point of the study. The intensity of the psychodysleptic effects will be assessed by patients every 5 minutes from minute 0 to minute 0 + 60 minutes.

• Any other hemodynamic and respiratory adverse event

  The time of initiation of the ketamine or esketamine infusion defines the minute 0 time point of the study. The intensity of the psychodysleptic effects will be assessed by patients every 5 minutes from minute 0 to minute 0 + 60 minutes.

Study Arms (2)

low-dose esketamine

EXPERIMENTAL

Drug: Esketamine

low-dose ketamine

ACTIVE COMPARATOR

Drug: Ketamine

Interventions

Esketamine DRUG

A single slow intravenous injection of low-dose esketamine (0.15 mg/kg) over 10 minutes using an infusion pump.

low-dose esketamine

Ketamine DRUG

A single slow intravenous injection of low-dose ketamine (0,3 mg/kg) with an infusion pump, during 10 minutes

low-dose ketamine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients aged 18 or over,
• consulting our emergency department for a medical or traumatic pathology responsible for acute (less than 7 days old) and severe pain (greater than or equal to 6 on the Verbal Numerical Rating Scale, which has 11 levels from 0 = no pain to 10 = maximum imaginable pain).
• Free and informed consent given before the start of the trial.
• Patients affiliated to social security system.

You may not qualify if:

• Inability to quantify pain score ;
• proven or suspected intoxication (drug or alcohol) leading to consciousness disorders (Glasgow score less than or equal to 15) ;
• person under legal protection or deprived of liberty ;
• pregnant or breast-feeding patients ;
• known allergy to ketamine or esketamine ;
• history of drug addiction or dependence ;
• insufficiently controlled hyperthyroidism ;
• history of cerebral of myocardial infarction ;
• known severe heart failure ;
• existence of intracranial hypertension, glaucoma or ocular trauma ;
• unstable vital signs (systolic blood pressure \< 90 mmHg or \> 180, heart rate \< 50 per minute or \> 150, respiratory rate \< 10 per minute or \> 30) ;
• chronic treatment with aminophylline, theophylline or methylergometrine ;
• ongoing simultaneous participation in another study that could interfere with the treatment studied or the results of statistical analysis.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nice: lead

Study Sites (1)

CHU de NICE

Nice, Alpes-maritimes, 06000, France

Location

MeSH Terms

Conditions

Acute Pain

Interventions

Esketamine; Ketamine

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2025
• First Posted: February 28, 2025
• Study Start: May 6, 2025
• Primary Completion: May 5, 2026
• Study Completion: May 5, 2026
• Last Updated: May 14, 2026

Record last verified: 2026-05

Locations

FR (1)