Best hypnotic drug choice for rapid sequence induction in the operating room: a 3-arm randomized trial open-labelled with blinded evaluation of the primary outcome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Nantes

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

14 Apr 2025 → ongoing

Decision date (initial)

2025-03-14

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

French Ministry of Heath

External identifiers

EU CT number

2024-517582-16-00

ClinicalTrials.gov

NCT06733129

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

compare the efficacies of ketamine alone and ketamine-propofol combination compared to standard doses of propofol to achieve successful tracheal intubation on the first attempt without severe hemodynamic hypotension in patients at risk of aspiration of gastric contents in the operating room

Secondary objectives 2

1. to compare the efficacy of ketamine and / or ketamine-propofol combination compared to standard doses of propofol on the prevention of postoperative complications
2. to compare the tolerance of ketamine and / or ketamine-propofol combination compared to standard doses of propofol

Conditions and MedDRA coding

rapid sequence induction in the operating room

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. age between 18 – 80 years’ old
2. female and male
3. ≥ 1 risk factor of aspiration of gastric contents defined as : preoperative fasting period of less than 6 hours, occlusive syndrome, functional ileus, vomiting episode within the last 12 hours, orthopaedic trauma within the last 12 hours, medical history of symptomatic gastroesophageal reflux or hiatus, hernia or gastroparesis or dysautonomia or gastroesophageal surgery with sphincter dysfunction, failure to discontinue GLP1 analogue as recommended (exenatide, liraglutide, albiglutide, taspoglutide, lixisenatide)
4. patient requiring orotracheal intubation during general anaesthesia in the operating room
5. patient or his/her next of skin written informed consent or emergency procedure

Exclusion criteria 7

1. predicted impossible tracheal intubation (≥ 1 of the following criteria: patient with known intubation complications, Mallampati score IV, Thyromental Distance ≤ 4.0 cm, Mouth Opening < 3 cm, Sternomental Distance < 12.5 cm, significant modification of the airway due to congenital, cancer, trauma or burning lesions (non-exhaustive list))
2. preoperative arterial hypotension (MAP < 65 mmHg or under catecholamine)
3. preoperative respiratory distress syndrome (SpO2 < 90% in room air)
4. contraindications to the use of ketamine and/or propofol and/or NMB
5. pregnancy or breast-feeding woman
6. patients under court protection or guardianship
7. absence of insurance covering health costs

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The composite primary outcome is the proportion of patients with successful intubation at first attempt and without post-induction hypotension defined by a mean arterial pressure ≤ 60 mmHg within 10 minutes after the start of the hypnotic injection.

Secondary endpoints 13

1. compared between the three study groups : Components of the primary outcomes analyzed separately: 1/rates of arterial hypotension episodes as defined in primary endpoint within 10 minutes after induction of anaesthesia 2/rates of tracheal intubation at the first attempt
2. Related to secondary Aim (1). Efficacy of ketamine and / or ketamine-propofol combination compared to standard doses of propofol on the prevention of postoperative complications: In the operating theatre (within 10 minutes after the start of the hypnotic injection): intubation quality score (IDS-3) values, Cormack-Lehane score values and POGO score values
3. Related to secondary Aim (1). Efficacy of ketamine and / or ketamine-propofol combination compared to standard doses of propofol on the prevention of postoperative complications: In the operating theatre (within 10 minutes after the start of the hypnotic injection): time between administration of hypnotic (start of anesthetic induction) and tracheal intubation (defined as the 6th capnography curve)
4. Related to secondary Aim (1). Efficacy of ketamine and / or ketamine-propofol combination compared to standard doses of propofol on the prevention of postoperative complications: In the operating theatre (within 10 minutes after the start of the hypnotic injection): values of heart rate, SpO2 and systolic/diastolic/mean arterial pressure measuredevery 1 minute from pre-oxygenation to 10 minutes after the start of the hypnotic injection
5. Related to secondary Aim (1). Efficacy of ketamine and / or ketamine-propofol combination compared to standard doses of propofol on the prevention of postoperative complications: In the operating theatre (within 10 minutes after the start of the hypnotic injection): rates of pulmonary aspiration of gastric contents during the intubation procedure
6. Related to secondary Aim (1). Efficacy of ketamine and / or ketamine-propofol combination compared to standard doses of propofol on the prevention of postoperative complications: In the operating theatre (within 10 minutes after the start of the hypnotic injection): minimal value of SpO2 value during the 10 first minutes after anaesthesia induction
7. Related to secondary Aim (1). Efficacy of ketamine and / or ketamine-propofol combination compared to standard doses of propofol on the prevention of postoperative complications: In the operating theatre (within 10 minutes after the start of the hypnotic injection): rates of vasopressor use and volume of intravenous fluids for vascular filling (from entry into the operating theatre to induction and from induction to recovery room)
8. Related to secondary Aim (2). Tolerance of ketamine and / or ketamine-propofol combination compared to standard doses of propofol: In the recovery room: postoperative Nu-DESC score value compared with preoperative score
9. Related to secondary Aim (2). Tolerance of ketamine and / or ketamine-propofol combination compared to standard doses of propofol: In the recovery room: need of sedative therapy in the recovery room to treat a delirium episode.
10. Related to secondary Aim (2). Tolerance of ketamine and / or ketamine-propofol combination compared to standard doses of propofol: Up to day 7: rates of major cardiovascular complications defined as: cardiac arrest, sustained arrhythmia, myocardial infarction, stroke (total, ischaemic, and haemorrhagic), coronary revascularization or admission to ICU for acute heart failure
11. Related to secondary Aim (2). Tolerance of ketamine and / or ketamine-propofol combination compared to standard doses of propofol: Up to day 7: rates of mortality at day 7
12. Related to secondary Aim (1). Efficacy of ketamine and / or ketamine-propofol combination compared to standard doses of propofol on the prevention of postoperative complications: In the operating theatre (within 10 minutes after the start of the hypnotic injection): - rates of failure of tracheal intubation after the first attempt
13. Related to secondary Aim (1). Efficacy of ketamine and / or ketamine-propofol combination compared to standard doses of propofol on the prevention of postoperative complications: In the operating theatre (within 10 minutes after the start of the hypnotic injection):Use of ketamine and total dose during intervention and total dose of ketamine in recovery room.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Nantes

Sponsor organisation

Centre Hospitalier Universitaire De Nantes

Address

5 Allee De L Ile Gloriette, Cs 69301 Cs 69301

City

Nantes Cedex 1

Postcode

44093

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Dr Nicolas GRILLOT

Public contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Dr Nicolas GRILLOT

Locations

1 EU/EEA country · 22 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 13 files

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

Application history

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