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出境医 / 临床实验 / Assessment of Remifentanil for Rapid Sequence Induction and Intubation in Full Stomach Patient Compared to Muscle Relaxant (REMICRUSH)

Assessment of Remifentanil for Rapid Sequence Induction and Intubation in Full Stomach Patient Compared to Muscle Relaxant (REMICRUSH)

Study Description
Brief Summary:
REMICrush is a French multicentric non inferiority simple blind randomized clinical trial that will compare the use of Remifentanil to muscle relaxant (reference treatment) for anesthetic rapid sequence intubation in terms of major complications (difficult intubation, gastric liquid aspiration, desaturation, hemodynamics reaction, ventricular arrhythmia, anaphylactic reaction).

Condition or disease Intervention/treatment Phase
Intra-tracheal Intubation Drug: Remifentanil group Drug: neuromuscular blockade group Phase 3

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Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized controlled trial in 2 parallel groups assigned to tested drug in intervention group and to reference treatment for control group.
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: Assessment of Remifentanil for Rapid Sequence Induction and Intubation in Full Stomach Patient Compared to Muscle Relaxant. A Non-inferiority Simple Blind Randomized Controlled Trial
Actual Study Start Date : October 9, 2019
Actual Primary Completion Date : April 22, 2021
Actual Study Completion Date : April 22, 2021
Arms and Interventions
Arm Intervention/treatment
Experimental: Remifentanil group
bolus intravenous injection of 3 to 4µg/kg of remifentanil after hypnotic administration for a crush anesthetic induction
Drug: Remifentanil group
bolus intravenous injection of 3 to 4µg/kg of remifentanil after hypnotic administration for a crush anesthetic induction

Active Comparator: Neuromuscular blockade group
Bolus intravenous injection of 1mg/kg of Succinylcholine or Rocuronium after hypnotic administration for a crush anesthetic induction
Drug: neuromuscular blockade group
Bolus intravenous injection of 1mg/kg of Succinylcholine or Rocuronium after hypnotic administration for a crush anesthetic induction

Outcome Measures
Primary Outcome Measures :
  1. Rate of tracheal intubation without major complication [ Time Frame: Day 7 from randomization ]

    Primary endpoint is the rate of tracheal intubation without major complications as defined by

    1. tracheal intubation with less than 2 laryngoscopies
    2. no aspiration during the 10 minutes after induction
    3. no desaturation under 95% during the 10 minutes after induction
    4. no hypo or hypertension as defined by a MAP<50mmHg or >110mmHg
    5. no ventricular arrhythmia involving an emergency treatment or cardiac arrest during the 10 minutes after induction
    6. no grade III or IV anaphylactic reaction during the 10 minutes after induction


Secondary Outcome Measures :
  1. quality of intubation: score IDS3 [ Time Frame: At Day 7 ]
    score IDS3 is a composite score for evaluating the difficulty of intubation under laryngoscopy.

  2. level of intubation difficulty [ Time Frame: within 10 minutes ]

    Cormack Lehane score This score describes laryngoscopic views during orotracheal intubation:

    • Cormack 1: The glottis is seen in its entirety
    • Cormack 2: Only the posterior half of the glottis is seen
    • Cormack 3: Only a tiny part of the glottis is seen
    • Cormack 4: The glottis is hidden by the epiglottis and tongue.

  3. Intubation difficulty evaluated by Percentage of opening of the gluteal opening [ Time Frame: within 10 minutes ]

    Evaluated by POGO (Percentage of opening of the gluteal opening) The opening of the orifice is defined by the distance between the anterior and posterior corners of the glottis.

    • A POGO score of 0% means that the glottic opening is not visible.
    • A POGO score of 100% means that the entire glottic gap is visible

  4. use of alternative technic [ Time Frame: within 10 minutes ]
    frequency of alternative technic use

  5. induction-intubation delay [ Time Frame: Within 7 days ]
    delay between hypnotic injection and apparition of the sixth capnographic curve

  6. desaturation [ Time Frame: within 10 minutes ]
    frequency of saturation between 80 et 95% and under 80% following anesthetic induction

  7. severe hemodynamic reaction [ Time Frame: within 10 minutes ]
    proportion of patients with cardiac frequency under 45 or above 110 and / or systolic arterial pressure under 80 mmHg or above 160 mmHg and or mean arterial pressure under 55mmHg or above 100 mmHg during the ten minutes following induction

  8. teeth/ tracheal trauma [ Time Frame: At day 7 ]
    proportion of patient with teeth or tracheal (endoscopic exam) trauma

  9. Allergies [ Time Frame: within 10 minutes ]
    proportion of patients with grade I or II anaphylactic reaction

  10. postoperative sore throat [ Time Frame: 1 hour after extubation ]

    POST grade (postoperative sore throat) is evaluated at 1 h after extubation

    Grade 0 = No pain Grade 1 = Mild pain (complains of pain on request) Grade 2 = Moderate pain (complains of pain spontaneously) Grade 3 = Severe pain (voice change, hoarseness, aphonia)


  11. post operative pneumonia [ Time Frame: At day 7 ]
    proportion of patients who developed pneumonia at day 7 of hospitalization, as defined by new lung infiltration at chest X-ray or tomodensitometry scanner associated with at least one of the following symptom : new purulent expectoration, change of chronic expectorations, fever> 38°C, leukocyte count < 4000/mL or > 12000/mL, positive blood culture and pathogen identification on respiratory sample

  12. Proportion of patients with post-operative respiratory distress [ Time Frame: At day 7 ]
    proportion of patients who developed post-operative respiratory distress within 7 days of hospitalization defined by acute respiratory failure with hypoxemia, PaO2/FiO2 ratio < 300 mmHg, new bilateral infiltrations on chest X-ray without cardiac etiology

  13. In hospital mortality [ Time Frame: At day 7 ]
    proportion of patients who died in hospital


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • - male or female
  • aged from 18 to 80 years old
  • surgery requiring general anaesthesia with tracheal with oro-tracheal intubation
  • Rapid sequence intubation indication
  • aspiration risk defined as : fasting < 6h00, digestive occlusion, functional ileus, vomiting < 12h00, orthopaedic trauma < 12h00, severe gastric reflux, gastroparesis and/or dysautonomia and or gastro-oesophagus surgery
  • signed informed consent sheet ; or emergency procedure if impossible

Exclusion Criteria:

  • planned impossible intubation
  • suspected/known allergy to neuromuscular blockade or remifentanil
  • Neuromuscular disease forbidding neuromuscular blockade use
  • Prolonged neuromuscular block former episode
  • Malignant hyperthermia former episode
  • Pre-operative respiratory failure (spO2< 95%)
  • Pre-operative hemodynamic failure (use of vasopressor)
  • cardiac arrest
  • A woman of childbearing age who has an active pregnancy and/or clinical signs suggestive of an active pregnancy and/or does not have a contraceptive or contraceptive method and has had unprotected sex within 15 days of the last menstrual period.
  • Patients under justice protection
  • Use of etomidate for anesthetic induction
Contacts and Locations

Locations
Layout table for location information
France
University Hospital
Angers, France
Military Hospital
Brest, France
University Hospital
Brest, France
University Hospital
Grenoble, France
CHD Vendée
La Roche-sur-Yon, France
Hospital
Le Mans, France
University hospital (SALENGRO hospital)
Lille, France
University Hospital
Lille, France
University Hospital Lyon Sud
Lyon, France
Le Confluent
Nantes, France
University Hospital
Nantes, France
Toulouse University Hospital
Toulouse, France
Hospital
Valenciennes, France
Sponsors and Collaborators
Nantes University Hospital
Tracking Information
First Submitted Date  ICMJE May 21, 2019
First Posted Date  ICMJE May 23, 2019
Last Update Posted Date April 27, 2021
Actual Study Start Date  ICMJE October 9, 2019
Actual Primary Completion Date April 22, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 22, 2019)
Rate of tracheal intubation without major complication [ Time Frame: Day 7 from randomization ]
Primary endpoint is the rate of tracheal intubation without major complications as defined by
  1. tracheal intubation with less than 2 laryngoscopies
  2. no aspiration during the 10 minutes after induction
  3. no desaturation under 95% during the 10 minutes after induction
  4. no hypo or hypertension as defined by a MAP<50mmHg or >110mmHg
  5. no ventricular arrhythmia involving an emergency treatment or cardiac arrest during the 10 minutes after induction
  6. no grade III or IV anaphylactic reaction during the 10 minutes after induction
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 23, 2019)
  • quality of intubation: score IDS3 [ Time Frame: At Day 7 ]
    score IDS3 is a composite score for evaluating the difficulty of intubation under laryngoscopy.
  • level of intubation difficulty [ Time Frame: within 10 minutes ]
    Cormack Lehane score This score describes laryngoscopic views during orotracheal intubation:
    • Cormack 1: The glottis is seen in its entirety
    • Cormack 2: Only the posterior half of the glottis is seen
    • Cormack 3: Only a tiny part of the glottis is seen
    • Cormack 4: The glottis is hidden by the epiglottis and tongue.
  • Intubation difficulty evaluated by Percentage of opening of the gluteal opening [ Time Frame: within 10 minutes ]
    Evaluated by POGO (Percentage of opening of the gluteal opening) The opening of the orifice is defined by the distance between the anterior and posterior corners of the glottis.
    • A POGO score of 0% means that the glottic opening is not visible.
    • A POGO score of 100% means that the entire glottic gap is visible
  • use of alternative technic [ Time Frame: within 10 minutes ]
    frequency of alternative technic use
  • induction-intubation delay [ Time Frame: Within 7 days ]
    delay between hypnotic injection and apparition of the sixth capnographic curve
  • desaturation [ Time Frame: within 10 minutes ]
    frequency of saturation between 80 et 95% and under 80% following anesthetic induction
  • severe hemodynamic reaction [ Time Frame: within 10 minutes ]
    proportion of patients with cardiac frequency under 45 or above 110 and / or systolic arterial pressure under 80 mmHg or above 160 mmHg and or mean arterial pressure under 55mmHg or above 100 mmHg during the ten minutes following induction
  • teeth/ tracheal trauma [ Time Frame: At day 7 ]
    proportion of patient with teeth or tracheal (endoscopic exam) trauma
  • Allergies [ Time Frame: within 10 minutes ]
    proportion of patients with grade I or II anaphylactic reaction
  • postoperative sore throat [ Time Frame: 1 hour after extubation ]
    POST grade (postoperative sore throat) is evaluated at 1 h after extubation Grade 0 = No pain Grade 1 = Mild pain (complains of pain on request) Grade 2 = Moderate pain (complains of pain spontaneously) Grade 3 = Severe pain (voice change, hoarseness, aphonia)
  • post operative pneumonia [ Time Frame: At day 7 ]
    proportion of patients who developed pneumonia at day 7 of hospitalization, as defined by new lung infiltration at chest X-ray or tomodensitometry scanner associated with at least one of the following symptom : new purulent expectoration, change of chronic expectorations, fever> 38°C, leukocyte count < 4000/mL or > 12000/mL, positive blood culture and pathogen identification on respiratory sample
  • Proportion of patients with post-operative respiratory distress [ Time Frame: At day 7 ]
    proportion of patients who developed post-operative respiratory distress within 7 days of hospitalization defined by acute respiratory failure with hypoxemia, PaO2/FiO2 ratio < 300 mmHg, new bilateral infiltrations on chest X-ray without cardiac etiology
  • In hospital mortality [ Time Frame: At day 7 ]
    proportion of patients who died in hospital
Original Secondary Outcome Measures  ICMJE
 (submitted: May 22, 2019)
  • quality of intubation: score IDS3 [ Time Frame: At Day 7 ]
    score IDS3 is a composite score for evaluating the difficulty of intubation under laryngoscopy.
  • level of intubation difficulty [ Time Frame: within 10 minutes ]
    Cormack Lehane score This score describes laryngoscopic views during orotracheal intubation:
    • Cormack 1: The glottis is seen in its entirety
    • Cormack 2: Only the posterior half of the glottis is seen
    • Cormack 3: Only a tiny part of the glottis is seen
    • Cormack 4: The glottis is hidden by the epiglottis and tongue.
  • Intubation difficulty evaluated by Percentage of opening of the gluteal opening [ Time Frame: within 10 minutes ]
    Evaluated by POGO (Percentage of opening of the gluteal opening) The opening of the orifice is defined by the distance between the anterior and posterior corners of the glottis.
    • A POGO score of 0% means that the glottic opening is not visible.
    • A POGO score of 100% means that the entire glottic gap is visible
  • use of alternative technic [ Time Frame: within 10 minutes ]
    frequency of alternative technic use
  • induction-intubation delay [ Time Frame: Within 7 days ]
    delay between hypnotic injection and apparition of the sixth capnographic curve
  • desaturation [ Time Frame: within 10 minutes ]
    frequency of saturation between 80 et 95% and under 80% following anesthetic induction
  • severe hemodynamic reaction [ Time Frame: within 10 minutes ]
    proportion of patients with cardiac frequency under 45 or above 110 and / or systolic arterial pressure under 80 mmHg or above 160 mmHg and or mean arterial pressure under 55mmHg or above 100 mmHg during the ten minutes following induction
  • teeth/ tracheal trauma [ Time Frame: At day 7 ]
    proportion of patient with teeth or tracheal (endoscopic exam) trauma
  • Allergies [ Time Frame: within 10 minutes ]
    proportion of patients with grade I or II anaphylactic reaction
  • postoperative sore throat [ Time Frame: 1 hour after extubation ]
    POST score is evaluated at 1 h after extubation
  • post operative pneumonia [ Time Frame: At day 7 ]
    proportion of patients who developed pneumonia at day 7 of hospitalization, as defined by new lung infiltration at chest X-ray or tomodensitometry scanner associated with at least one of the following symptom : new purulent expectoration, change of chronic expectorations, fever> 38°C, leukocyte count < 4000/mL or > 12000/mL, positive blood culture and pathogen identification on respiratory sample
  • Proportion of patients with post-operative respiratory distress [ Time Frame: At day 7 ]
    proportion of patients who developed post-operative respiratory distress within 7 days of hospitalization defined by acute respiratory failure with hypoxemia, PaO2/FiO2 ratio < 300 mmHg, new bilateral infiltrations on chest X-ray without cardiac etiology
  • In hospital mortality [ Time Frame: At day 7 ]
    proportion of patients who died in hospital
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Assessment of Remifentanil for Rapid Sequence Induction and Intubation in Full Stomach Patient Compared to Muscle Relaxant
Official Title  ICMJE Assessment of Remifentanil for Rapid Sequence Induction and Intubation in Full Stomach Patient Compared to Muscle Relaxant. A Non-inferiority Simple Blind Randomized Controlled Trial
Brief Summary REMICrush is a French multicentric non inferiority simple blind randomized clinical trial that will compare the use of Remifentanil to muscle relaxant (reference treatment) for anesthetic rapid sequence intubation in terms of major complications (difficult intubation, gastric liquid aspiration, desaturation, hemodynamics reaction, ventricular arrhythmia, anaphylactic reaction).
Detailed Description

BACKGROUND: Rapid sequence intubation is the reference anaesthetic procedure for patient at risk of pulmonary aspiration of gastric contents (for example emergency procedure, bowel obstruction, obese patients, gastroesophageal reflux …) or difficult airway management. Nowadays the use of Succinylcholine (CELOCURINE), a neuromuscular blockade with a short duration of action, is recommended in this indication. However, several adverse events are frequently reported, especially anaphylactic reaction, restraining its use for rapid sequence intubation. Other adverse effects such as extended neuromuscular block, malignant hyperthermia or severe hyperkaliemia prohibit its use. In this case the use of another neuromuscular blockade, Rocuronium (ESMERON), is an alternative solution. Unfortunately, this other molecule causes as many anaphylactic event as Succinylcholine (1 anaphylactic event for 3000 uses) and produce a long duration of neuromuscular block. Incidence of anaphylactic reaction is increasing in France and mostly severe reactions. Its utilization is therefore reduced to 31 to 55% of crush induction despite the recommendations. Remifentanil is an opioid agent with very shorts delay and duration of action. Several study have shown similar intubation conditions in planned surgery with the use of Remifentanil instead of neuromuscular blockade and less hemodynamic reactions. Remifentanil is already approved for anesthetic induction and recognized as an alternative to neuromuscular blockade for the intubation of children. Use of remifentanil has shown satisfying intubation conditions for adults but its incidence of major complications compared to succinylcholine remains unknown.

Study hypothesis: The investigators thus hypothesized that Remifentanil is non inferior to neuromuscular blockade in terms of major complications after a crush induction.

Methods: A multicenter simple blind randomized controlled trial. 11 centers will participate in this project.

Experimental treatment arm: During anesthetic induction remifentanil will be injected immediately after hypnotic drug through bolus intravenous injection by a peripheral or verified central venous access, at 3 to 4 µg/kg. Orotracheal intubation will be performed 30 to 60 seconds later by a graduated anesthesiologist or a resident with 4 validated semesters.

Control arm treatment: A neuromuscular blockade will be injected right after the hypnotic drug. Whether succinylcholine (CELOCURINE) at 1mg/kg or Rocuronium (ESMERON) at 1mg/kg in a bolus intravenous injection by a peripheral or verified central venous access. Orotracheal intubation will be performed after occurring of fasciculations with succinylcholine or 30 to 60 seconds after injection of Rocuronium by a graduated anesthesiologist or a resident with 4 validated semesters.

Objective and judgment criteria: The primary objective is to demonstrate non inferiority of Remifentanil compared to neuromuscular blockade in terms of major complications after a crush induction. Primary endpoint is the rate of tracheal intubation without major complications as defined by 1/ tracheal intubation with less than 2 laryngoscopies 2/ no aspiration during the 10 minutes after induction 3/ no desaturation under 95% during the 10 minutes after induction 4/ no hypo or hypertension as defined by a Median blood pressure<50 mmHg or >110 mmHg 5/ NO ventricular arrhythmia involving an emergency treatment or cardiac arrest during the 10 minutes after induction 6/ No grade III or IV anaphylactic reaction after the 10 minutes after induction.

Statistical analyses:

A 80% incidence of intubation without major complication was hypothesized. Non inferiority has been set under a superior limit of 7% for the primary endpoint 95% of the proportions difference between intervention and control group. In order to achieve 80 power with a 5% alpha risk, 1150 patients (575 for each arms) are to be included.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Randomized controlled trial in 2 parallel groups assigned to tested drug in intervention group and to reference treatment for control group.
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Supportive Care
Condition  ICMJE Intra-tracheal Intubation
Intervention  ICMJE
  • Drug: Remifentanil group
    bolus intravenous injection of 3 to 4µg/kg of remifentanil after hypnotic administration for a crush anesthetic induction
  • Drug: neuromuscular blockade group
    Bolus intravenous injection of 1mg/kg of Succinylcholine or Rocuronium after hypnotic administration for a crush anesthetic induction
Study Arms  ICMJE
  • Experimental: Remifentanil group
    bolus intravenous injection of 3 to 4µg/kg of remifentanil after hypnotic administration for a crush anesthetic induction
    Intervention: Drug: Remifentanil group
  • Active Comparator: Neuromuscular blockade group
    Bolus intravenous injection of 1mg/kg of Succinylcholine or Rocuronium after hypnotic administration for a crush anesthetic induction
    Intervention: Drug: neuromuscular blockade group
Publications * Grillot N, Garot M, Lasocki S, Huet O, Bouzat P, Le Moal C, Oudot M, Chatel-Josse N, El Amine Y, Danguy des Déserts M, Bruneau N, Cinotti R, David JS, Langeron O, Minville V, Tching-Sin M, Faurel-Paul E, Lerebourg C, Flattres-Duchaussoy D, Jobert A, Asehnoune K, Feuillet F, Roquilly A. Assessment of remifentanil for rapid sequence induction and intubation in patients at risk of pulmonary aspiration of gastric contents compared to rapid-onset paralytic agents: study protocol for a non-inferiority simple blind randomized controlled trial (the REMICRUSH study). Trials. 2021 Mar 30;22(1):237. doi: 10.1186/s13063-021-05192-x.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 22, 2019)
1150
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE April 22, 2021
Actual Primary Completion Date April 22, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • - male or female
  • aged from 18 to 80 years old
  • surgery requiring general anaesthesia with tracheal with oro-tracheal intubation
  • Rapid sequence intubation indication
  • aspiration risk defined as : fasting < 6h00, digestive occlusion, functional ileus, vomiting < 12h00, orthopaedic trauma < 12h00, severe gastric reflux, gastroparesis and/or dysautonomia and or gastro-oesophagus surgery
  • signed informed consent sheet ; or emergency procedure if impossible

Exclusion Criteria:

  • planned impossible intubation
  • suspected/known allergy to neuromuscular blockade or remifentanil
  • Neuromuscular disease forbidding neuromuscular blockade use
  • Prolonged neuromuscular block former episode
  • Malignant hyperthermia former episode
  • Pre-operative respiratory failure (spO2< 95%)
  • Pre-operative hemodynamic failure (use of vasopressor)
  • cardiac arrest
  • A woman of childbearing age who has an active pregnancy and/or clinical signs suggestive of an active pregnancy and/or does not have a contraceptive or contraceptive method and has had unprotected sex within 15 days of the last menstrual period.
  • Patients under justice protection
  • Use of etomidate for anesthetic induction
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03960801
Other Study ID Numbers  ICMJE RC19_0055
2019-000753-31 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Nantes University Hospital
Study Sponsor  ICMJE Nantes University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Nantes University Hospital
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP