Best Hypnotic Drug Choice for Rapid Sequence Induction in the Operating Room (HYPNOTIKS)

Best Hypnotic Drug Choice for Rapid Sequence Induction in the Operating Room: a 3-arm Randomized Trial

The best hypnotic choice to optimize the balance between good intubation condition quality and hemodynamic stability during RSI performed in the operating theatre remained to be investigated.

Therefore, a randomized study evaluating the efficacy of propofol, ketamine, and a combination of both is appropriate. So, we designed the HyPnotiKs randomized controlled study to investigate the efficacy of these hypnotic drugs in patients undergoing RSI in the operating theatre. The primary endpoint will be the successful tracheal intubation at the first attempt without major arterial hypotension event.

Study Overview

• Status: Recruiting
• Conditions: Rapid Sequence Induction
• Intervention / Treatment: Drug: combination of Ketamine and Propofol; Drug: direct IV injection

• Study Type: Interventional
• Enrollment (Estimated): 1218
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Nicolas GRILLOT, MD; Phone Number: +33 02 53 48 22 24; Email: nicolas.grillot@chu-nantes.fr

Study Locations

• France
  • Angers, France
    • Recruiting
    • Chr Angers
    • Contact: Sigismond LASOCKI; Phone Number: +33 02 41 35 36 35; Email: silasocki@chu-angers.fr
    • Principal Investigator: Sigismond LASOCKI
  • Brest, France
    • Recruiting
    • Chru de Brest Hopital Cavale Blanche
    • Contact: Anais CAILLARD; Phone Number: +33 02 98 34 76 23; Email: anais.caillard@chu-brest.fr
    • Principal Investigator: Anais CAILLARD
  • Chartres, France
    • Not yet recruiting
    • CH Louis Pasteur
    • Contact: Nidhal CHEBBI
    • Principal Investigator: Nidhal CHEBBI
  • Dijon, France
    • Recruiting
    • CHU Dijon
    • Contact: Pierre-Grégoire GUINOT; Phone Number: +33 03 80 28 15 54; Email: guinotpierregregoire@gmail.com
    • Principal Investigator: Pierre-Grégoire GUINOT
  • Grenoble, France
    • Not yet recruiting
    • Chu Grenoble Alpes
    • Contact: Pierre BOUZAT; Phone Number: +33 04 76 76 72 53; Email: PBouzat@chu-grenoble.fr
    • Principal Investigator: Pierre BOUZAT
  • La Roche-sur-Yon, France
    • Recruiting
    • CHD Vendee
    • Contact: Mathieu OUDOT; Phone Number: +33 02 51 44 62 37; Email: Mathieu.oudot@chd-vendee.fr
    • Principal Investigator: Mathieu OUDOT
  • Le Kremlin-Bicêtre, France
    • Not yet recruiting
    • APHP Bicêtre
    • Contact: Samy FIGUEIREDO; Phone Number: +33 01 45 21 34 41; Email: samy.figueiredo@aphp.fr
    • Principal Investigator: Samy FIGUEIREDO
  • Le Mans, France
    • Recruiting
    • CH Le mans
    • Contact: Laurent BLANCHET; Phone Number: +33 02 43 43 28 40; Email: lblanchet@ch-lemans.fr
    • Principal Investigator: Laurent BLANCHET
  • Lille, France
    • Recruiting
    • CHU Lille Hopital Salengro
    • Contact: Nathalie BRUNEAU; Phone Number: +33 03 20 44 59 62; Email: nathaliemarie.bruneau@chru-lille.fr
    • Principal Investigator: Nathalie BRUNEAU
  • Lille, France
    • Recruiting
    • CHU Lille Hôpital Claude Huriez
    • Contact: Cédric CIRENEI; Phone Number: +33 03 20 44 59 62; Email: cedric.cirenei@chu-lille.fr
    • Principal Investigator: cedric CIRENEI
  • Lyon, France
    • Not yet recruiting
    • CHU Lyon Hôpital Sud
    • Contact: Jean-Stephane DAVID; Phone Number: +33 04 72 11 73 11; Email: jean-stephane.david@univ-lyon1.fr
    • Principal Investigator: Jean-Stéphane DAVID
  • Lyon, France
    • Not yet recruiting
    • HCL Lyon Croix-Rousse
    • Contact: Alice BLET; Phone Number: 04 72 07 12 39; Email: alice.blet@chu-lyon.fr
    • Principal Investigator: Alice BLET
    • Principal Investigator: Pascal INFANTINO
  • Nantes, France, 44093
    • Recruiting
    • CHU Nantes
    • Contact: Nicolas GRILLOT, MD; Phone Number: +33 02 53 48 22 24; Email: nicolas.grillot@chu-nantes.fr
    • Principal Investigator: Antoine ROQUILLY
  • Nantes, France, 44093
    • Recruiting
    • Chu Nantes (Laennec)
    • Contact: Xavier AMBROSI; Phone Number: +33 02 53 48 27 85; Email: xavier.ambrosi@chu-nantes.fr
    • Principal Investigator: Xavier AMBROSI
  • Paris, France
    • Not yet recruiting
    • APHP St-Antoine
    • Contact: Franck VERDON; Phone Number: +33 01 71 97 70 70; Email: franck.verdonk@aphp.fr
    • Principal Investigator: Franck VERDON
  • Paris, France
    • Not yet recruiting
    • APHP Tenon
    • Contact: Franck VERDONK; Phone Number: +33 01 71 97 70 70; Email: franck.verdonk@aphp.fr
    • Principal Investigator: Franck VERDONK
  • Poitiers, France
    • Recruiting
    • CHU Poitiers
    • Contact: Quentin SAINT GENIS; Phone Number: +33 05 49 44 38 95; Email: quentin.saint-genis@chu-poitiers.fr
    • Principal Investigator: Quentin SAINT-GENIS
  • Suresnes, France
    • Recruiting
    • Hopital Foch
    • Contact: Morgan LE GUEN
    • Principal Investigator: Morgan LE GUEN
  • Toulouse, France
    • Not yet recruiting
    • CHU Toulouse Hôpital Purpan
    • Contact: Maxime POMMIER; Phone Number: +33 05 61 77 23 88; Email: pommier.max@chu-toulouse.fr
    • Principal Investigator: Maxime POMMIER
  • Toulouse, France
    • Not yet recruiting
    • Chu Toulouse Hopital Rangueil
    • Contact: Francois LABASTE; Phone Number: +33 05 61 32 28 22; Email: labaste.f@chu-toulouse.fr
    • Principal Investigator: Francois LABASTE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• age between 18 - 80 years' old

• female* and male

  • ≥ 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)
• patient requiring orotracheal intubation during general anaesthesia in the operating room.
• patient or his/her next of kin written informed consent or emergency procedure
• failure to discontinue GLP1 analogue as recommended (exenatide, liraglutide, albiglutide, taspoglutide, lixisenatide)

Exclusion Criteria:

• 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)) [30]
• preoperative arterial hypotension (MAP < 65 mmHg or under catecholamine)
• preoperative respiratory distress syndrome (SpO2 < 90% in room air)

• contraindications to the use of ketamine and/or propofol and/or NMB:

  • allergy to the active substance or to one of the excipients or to soy or peanuts,
  • porphyria
  • intracranial hypertension
  • uncontrolled arterial hypertension (systolic arterial pressure > 180 mmHg)
  • personal or family history of known malignant hyperthermia, congenital muscular dystrophy, myasthenia, a known congenital deficit in plasma pseudocholinesterase
• pregnancy or breast-feeding woman
• patients under court protection or guardianship
• absence of insurance covering health costs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KETOFOL; Ketofol: combination of Ketamine and Propofol : consecutive direct IV injection of Ketamine 1 mg/kg and Propofol 1 mg/kg after completing pre-oxygenation	Drug: combination of Ketamine and Propofol; combination of Ketamine and Propofol described above: consecutive direct IV injection of Ketamine 1 mg/kg and Propofol 1 mg/kg (adjusted body weight if BMI > 30). Dilution are not necessary.
Experimental: KETAMINE; direct IV injection at dosage of 2 mg/kg after completing pre-oxygenation	Drug: direct IV injection; direct IV injection at dosage of 2 mg/kg (adjusted body weight if BMI > 30) after completing pre-oxygenation
Active Comparator: PROPOFOL; direct IV injection at dosage of 2 mg/kg after completing pre-oxygenation.	Drug: direct IV injection; direct IV injection at dosage of 2 mg/kg (adjusted body weight if BMI > 30) after completing pre-oxygenation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of patients with successful intubation at first attempt and without post-induction hypotension	The main objective of the study is to 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 hemodynamic hypotension in patients at risk of aspiration of gastric contents in the operating room. 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.	within 10 minutes after the start of the hypnotic injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rates of arterial hypotension episodes	rates of arterial hypotension episodes as defined in primary endpoint within 10 minutes after induction of anaesthesia compared between the three study groups	within 10 minutes after the start of the hypnotic injection
rates of tracheal intubation at the first attempt	rates of tracheal intubation at the first attempt compared between the three study groups	within 10 minutes after the start of the hypnotic injection
quality of the intubation	In the operating theatre (within 10 minutes after the start of the hypnotic injection): intubation difficulty scale (IDS-3) values	within 10 minutes after the start of the hypnotic injection
quality of the intubation	In the operating theatre (within 10 minutes after the start of the hypnotic injection): Cormack-Lehane score values (from 1 to 4); Cormack 1: The glottis is seen in its entirety; Cormack 2: Only the posterior half of the glottis is seen; Cormack 3: Only a small part of the glottis is seen; Cormack 4: The glottis is hidden by the epiglottis and tongue.	within 10 minutes after the start of the hypnotic injection
time between administration of hypnotic and tracheal intubation	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)	within 10 minutes after the start of the hypnotic injection
values of heart rate	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 measured every 1 minute from pre-oxygenation to 10 minutes after the start of the hypnotic injection	within 10 minutes after the start of the hypnotic injection
values of SpO2	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): SpO2 measured every 1 minute from pre-oxygenation to 10 minutes after the start of the hypnotic injection	within 10 minutes after the start of the hypnotic injection
rates of pulmonary aspiration of gastric contents	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	within 10 minutes after the start of the hypnotic injection
Tolerance of ketamine and / or ketamine-propofol combination compared to standard doses of propofol	Tolerance of ketamine and / or ketamine-propofol combination compared to standard doses of propofol in the recovery room by postoperative Nu-DESC (Nursing Delirium Screening Scale) score value compared with preoperative score From 0 to 10	during stay in the recovery room
Tolerance of ketamine and / or ketamine-propofol combination compared to standard doses of propofol	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.	during stay in the recovery room
Tolerance of ketamine and / or ketamine-propofol combination compared to standard doses of propofol	Tolerance of ketamine and / or ketamine-propofol combination compared to standard doses of propofol in the recovery room: 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; rates of mortality at day 7	within 7 days after the start of the hypnotic injection
values of blood pressure	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): systolic/diastolic/mean blood pressure measured every 1 minute from pre-oxygenation to 10 minutes after the start of the hypnotic injection	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)	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)	within 10 minutes after the start of the hypnotic injection
volume of intravenous fluids for vascular filling	volume of intravenous fluids for vascular filling (from entry into the operating theatre to induction and from induction to recovery room)	up to relapse of the recovery room (up to 7 days after surgery)
Tolerance of ketamine and / or ketamine-propofol combination compared to standard doses of propofol	Tolerance of ketamine and / or ketamine-propofol combination compared to standard doses of propofol in the recovery room: Use of ketamine and total dose during intervention and total dose of ketamine in recovery room.	during stay in the recovery room (up to 7 days after induction)

Collaborators and Investigators

• Sponsor: Nantes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2025
• Primary Completion (Estimated): April 14, 2027
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: December 2, 2024
• First Submitted That Met QC Criteria: December 9, 2024
• First Posted (Actual): December 13, 2024

Study Record Updates

• Last Update Posted (Actual): December 2, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: general anesthesia; ketamine; propofol; Rapid sequence induction; hypotension; ketofol; Full stomach patient
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypotension; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Propofol
• Other Study ID Numbers: RC24_0389

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No