Ketamine Low dOse Evaluation on morphine consumption in traumatic patient

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Marseille

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]

Trial duration

5 Aug 2022 → ongoing

Decision date (initial)

2024-07-31

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Internal Funding (Appel d'Offre Recherche Clinique)

External identifiers

EU CT number

2023-510016-39-00

EudraCT number

2020-004812-81

ClinicalTrials.gov

NCT04833816

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Demonstrate a significant reduction of at least 25% in opioid consumption at 48 hours in the management of severe trauma, while demonstrating non-inferiority in terms of analgesia.

Secondary objectives 7

1. Compare cumulative doses of opioids administered during the first 5 days of management.
2. Compare mean VAS during the first 5 days of treatment.
3. Compare the rate of occurrence of delirium between the 2 groups during resuscitation.
4. Compare the rate of occurrence of complications between the 2 groups occurring during resuscitation (urinary retention, nausea, vomiting, delirium, hemodynamic instability, hypertensive crisis, neurological distress (seizure), respiratory distress, changes in liver function
5. Compare mean length of stay between the 2 groups in intensive care and in hospital.
6. Compare the rate of occurrence of chronic pain at 3 months of care between the 2 groups, using a validated questionnaire.
7. Compare morphine consumption at 3 months.

Conditions and MedDRA coding

Traumatism

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male or female over 18
2. Trauma patient with at least 2 lesions in two different regions as defined by the ISS (injury severity score) (Head or neck, Face, Thorax, Abdomen and pelvic contents, Limbs or pelvic girdle, External (entire skin surface) or trauma patient with at least 2 orthopedic lesions in the AIS region "limbs or pelvic girdle" combining 2 different limbs or 1 limb and the pelvic girdle.
3. Patient with at least two regional or orthopedic injuries classified as moderate to maximal, defined by an AIS (Abbreviated Injury Scale) > 1.
4. Patient with signed informed consent
5. Patient entitled to or affiliated with a social security scheme.

Exclusion criteria 16

1. Patients with an indication for deep sedation (intracranial hypertension or acute respiratory distress syndrome).
2. Patients in whom the infusion could not be started within the first 12 hours of initial management in the investigating department.
3. Patients whose state of consciousness is incompatible with understanding the protocol.
4. Patients with chronic, unbalanced hypertension.
5. Patients with severe heart failure (defined as systolic ejection fraction < 30%).
6. Patients with a BMI > 35 kg/m² or a weight of over 120 kg.
7. Patient with chronic analgesic use, defined as opioid derivatives used for more than one week for an intercurrent illness.
8. Presence of a history of chronic pain.
9. Presence of a history of epilepsy not controlled by background treatment.
10. Presence of a history of psychosis or drug addiction.
11. Patients with a history of stroke of less than 3 months.
12. Patients allergic to ketamine or its excipients.
13. Patients allergic to sufentanil or paracetamol.
14. Pregnant or breast-feeding women.
15. Patients who do not understand French.
16. Patients under guardianship, curatorship or legal protection.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Total dose of sufentanil administered is deferred to 48 hours of management.

Secondary endpoints 9

1. Cumulative dose of opioids administered during the first 5 days of care.
2. Average VAS during the first 5 days of treatment.
3. Rate of delirium according to the CAM-ICU scale
4. Rate of occurrence and quantification of nausea and/or vomiting using a semi-quantitative method (absent, mild, moderate, severe) previously described
5. Rate of occurrence of acute urinary retention/urinary globe
6. Rate of occurrence of neurological distress (seizure) or hemodynamic distress (rhythm disturbance / cardiac arrest / hypertensive crisis defined as systolic blood pressure > 180mmHg without associated pain factor) or respiratory distress (orotracheal intubation for respiratory distress, use of non-invasive ventilation or high-flow oxygen therapy (>10L) for respiratory distress)
7. Rate of occurrence of a hepatic complication defined as an increase in liver enzymes (ALAT) of more than 3 times the high normal value, or an increase of more than 100% in initial bilirubin values, or a decrease in factor V below 50% in the absence of an explanation linked to the management of the trauma or hemorrhage.
8. Length of stay in intensive care unit and total length of hospitalization defined as the number of days between the date of admission and discharge from the intensive care unit and hospitalization.
9. Amount of analgesic treatment taken daily, overall quality of life, occurrence and quantification and location of potential chronic pain according to the SF-MPQ-2 and SPRINT and SF-36 questionnaires

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 Marseille

Sponsor organisation

Assistance Publique Hopitaux De Marseille

Address

80 Rue Brochier

City

Marseille

Postcode

13005

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Marseille

Contact name

Gary Duclos

Public contact point

Organisation

Assistance Publique Hopitaux De Marseille

Contact name

Gary Duclos

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 10 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