Rapid Sequence Intubation With Magnesium-rocuronium Compared With Succinylcholine - A Randomised Clinical Study (MagInRoc)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by University Hospital, Geneva
Sponsor:
Collaborator:
University of Lausanne Hospitals
Information provided by (Responsible Party):
Christoph Czarnetzki, University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT01571908
First received: April 3, 2012
Last updated: November 5, 2013
Last verified: November 2013
  Purpose

Magnesium accelerates the reaction of rocuronium, a neuromuscular blocker used for muscle relaxation to ease the intubation during anaesthesia.

Succinylcholine is a very fast reacting neuromuscular blocker. It is often used in emergency procedures, when rapid intubation is necessary.

We want to now if a perfusion of magnesium before anaesthesia accelerates to such an extent the reaction of rocuronium that intubation conditions are comparable or even better than with succinylcholine alone (prior perfusion of saline=placebo)


Condition Intervention Phase
Intubation Conditions
Drug: Magnesium perfusion
Drug: Rocuronium
Drug: Placebo perfusion
Drug: Succinylcholine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Rapid Sequence Intubation With Magnesium-rocuronium Compared With Succinylcholine - A Randomised Clinical Study

Resource links provided by NLM:


Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:
  • Intubation score [ Time Frame: Patient will be followed over 24 hours ] [ Designated as safety issue: No ]
    Intubation conditions will be evaluated using a published score that takes into account ease of laryngoscopy (easy, fair, difficult), vocal cords position (abducted, intermediate/moving, closed) and presence of diaphragmatic movement or coughing while inserting the tube (none, slight, vigorous/sustained). The final score summarises intubation conditions as excellent (all qualities are excellent), good (all qualities are either excellent or good), or poor (presence of a single quality listed under "poor").


Secondary Outcome Measures:
  • Signs of histamine release [ Time Frame: From start of anesthesia induction upto 30 minutes after intubation ] [ Designated as safety issue: Yes ]
    Immediately after intubation, patients will be evaluated for signs of histamine release (bronchospasm, erythema, oedema).

  • awareness and muscle pain [ Time Frame: 24 hour follow up ] [ Designated as safety issue: Yes ]
    The day after surgery, patients will be visited and will be screened for awareness and muscle pain.


Estimated Enrollment: 280
Study Start Date: September 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Magnesium perfusion - Rocuronium
60 mg/kg of magnesium perfusion over 15 minutes before Anaesthesia. After Anaesthesia induction 0.6 mg/kg of Rocuronium intravenously
Drug: Magnesium perfusion
The patient receives during 15 minutes a perfusion of 60mg/kg of Magnesium sulphate before induction of anaesthesia.
Other Name: Magnesium
Drug: Rocuronium
Immediately after anaesthesia induction and loss of consciousness 0,6 mg/kg of rocuronium will be injected
Other Name: Zemuron
Active Comparator: Placebo perfusion - Succinylcholine
1ml/kg of saline (placebo) over 15 minutes before Anaesthesia. After Anaesthesia induction 1 mg/kg of Succinylcholine intravenously
Drug: Placebo perfusion
The patient receives during 15 minutes a perfusion of 1 ml/kg of saline before induction of anaesthesia
Other Name: Saline
Drug: Succinylcholine
Immediately after anaesthesia induction at loss of consciousness 1 mg/kg of succinylcholine will be injected
Other Name: Anectine

Detailed Description:

Rapid sequence intubation (RSI) is the preferred method of endotracheal intubation in the emergency setting. The aim of RSI is to achieve rapid unconsciousness and complete neuromuscular blockade which facilitates endotracheal intubation. RSI is of particular importance in unfastened patients who are at risk of regurgitation and subsequent aspiration of stomach contents into the lungs during induction of anaesthesia.

Still today, succinylcholine is the neuromuscular blocking agent of choice for RSI. However, unfortunately in 60 at 80% the intubations conditions not are excellent and there are contraindications for the usage of succinylcholine and numerous side effects. Thus there is a need for alternative techniques that allow for rapid, high-quality and safe intubation conditions. Magnesium has an impact on neuromuscular transmission; it reduces the amount of acetylcholine that is released at the motor nerve terminal.

It has been shown that an IV infusion of magnesium sulphate prior to a standard intubation dose of rocuronium enhanced the speed of onset of the neuromuscular block compared with rocuronium alone by about 35% and there was much less variability in onset times. This makes the combination magnesium-rocuronium a potentially interesting alternative to succinylcholine for RSI.

The investigators objective is to compare in surgical patients during a standardized RSI procedure intubation conditions with rocuronium 0.6 mg kg-1 after pre-treatment with intravenous MgSO4 60 mg kg-1 (experimental intervention) with succinylcholine 1 mg kg-1 (control intervention) and to quantify any minor or major adverse event.

The investigators primary hypothesis is that with rocuronium 0.6 mg kg-1, after pre-treatment with MgSO4 60 mg kg-1, the rate of excellent intubation conditions will be higher (80%) compared with succinylcholine 1 mg kg-1 (60%).

This is a two centre (Division of Anaesthesiology, Geneva University Hospitals and Division of Anaesthesiology, University Hospital of Lausanne), stratified (male, female), randomized, double blinded study including 280 patients.

The investigators will compare in surgical patients during a standardized RSI procedure intubation conditions with rocuronium 0.6 mg kg-1 after pre-treatment with intravenous MgSO4 60 mg kg-1 (experimental intervention) with succinylcholine 1 mg kg-1 (control intervention).

Intubation conditions will be evaluated by the intubating anaesthesiologist following predefined criteria. The intubating anesthetist will not be present at study drug administration to guarantee blinding. Only two intubating anaesthetists will be identified per participating centre.

Rapid sequence intubation is a cornerstone of daily anaesthetic practice and succinylcholine is still the most frequently used neuromuscular agent in this context. In some patients, succinylcholine is contraindicated and therefore alternatives to this very fast reacting neuromuscular blocker are needed. If the investigators show that the investigators proposed magnesium-rocuronium regimen provides better intubation conditions as succinylcholine, the investigators study is likely to have an important impact on daily clinical practice.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult, age ≥18 to 65 years, male or female.
  • American Society of Anaesthesiology [ASA] status I or II.
  • Patient is able to read and understand the information sheet and to sign and date the consent form.
  • Patient scheduled of elective surgery lasting ≥60 minutes.
  • If the patient is female and of childbearing potential, she must have a negative pregnancy test.

Exclusion Criteria:

  • A history of allergy or hypersensitivity to rocuronium, succinylcholine or magnesium sulphate
  • Neuromuscular disease
  • History of malignant hyperthermia
  • Preoperative medications known to influence neuromuscular function (for instance, certain antibiotics [aminoglycosides], anticonvulsants [phenytoine], or IV lidocaine)
  • Electrolyte abnormalities* (for instance, hypermagnesemia or hyperkalemia)
  • Hepatic dysfunction* (i.e. bilirubin >1.5 x upper limit normal (ULN), alanine aminotransferase (ALT) >2.5 x ULN, aspartate aminotransferase (AST) >2.5 x ULN)
  • Renal insufficiency* (i.e. creatinine >1.5 x ULN, creatinine clearance < 60 ml min-1 1.73 m-2, estimated by the formula by Cockcroft-Gault)).
  • Atrioventricular heart block
  • Patients with magnesium treatment
  • Patients with a body mass index <19 or >28 kg m2
  • Pregnant or breastfeeding women
  • Expected difficult intubation or mask ventilation.
  • Patient having participated in any clinical trial within 30 days, inclusive, of signing the informed consent form of the current trial.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01571908

Contacts
Contact: Christoph A Czarnetzki, MD, MBA 0041223723311 christoph.czarnetzki@hcuge.ch
Contact: Martin R Tramèr, MD, PhD 0041223723311 martin.tramer@hcuge.ch

Locations
Switzerland
University Hospital of Geneva, Anesthesia Department Recruiting
Geneva, Canton of Geneva, Switzerland, 1211
Contact: Christoph A Czarnetzki, MD, MBA    0041223723311    christoph.czarnetzki@hcuge.ch   
Principal Investigator: Christoph A Czarnetzki, MD, MBA         
Sub-Investigator: Christopher Lysakowski, MD         
Division of Anaesthesiology, University Hospital of Lausanne (CHUV) Recruiting
Lausanne, Vaud, Switzerland, 1011
Contact: Sylvain Ganer, MD    004121 314 11 11    sylvain.gander@chuv.ch   
Contact: Christian Kern, MD, Prof    004121 314 11 11    christian.kern@chuv.ch   
Principal Investigator: Christian Kern, MD, Prof         
Sub-Investigator: Sylvain Gander, MD         
Sponsors and Collaborators
University Hospital, Geneva
University of Lausanne Hospitals
Investigators
Principal Investigator: Christoph Czarnetzki, MD, PD University hospitals of Geneva
Study Chair: Martin R Tramèr, MD, PhD University hospitals of Geneva
Principal Investigator: Christian Kern, MD, Prof University Hospitals of Lausanne, Switzerland
  More Information

No publications provided

Responsible Party: Christoph Czarnetzki, Responsable Investigator, University Hospital, Geneva
ClinicalTrials.gov Identifier: NCT01571908     History of Changes
Other Study ID Numbers: CER 11-235
Study First Received: April 3, 2012
Last Updated: November 5, 2013
Health Authority: Switzerland: Swissmedic

Keywords provided by University Hospital, Geneva:
rocuronium
succinylcholine
magnesiumsulphate
intubation conditions

Additional relevant MeSH terms:
Succinylcholine
Rocuronium
Neuromuscular Depolarizing Agents
Neuromuscular Blocking Agents
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Neuromuscular Nondepolarizing Agents

ClinicalTrials.gov processed this record on August 28, 2014