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Role of Neutrophil Activation in Anaphylaxis to Neuro-Muscular Blocking Agents (NASA)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01637220
First Posted: July 11, 2012
Last Update Posted: December 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
  Purpose

In about 10% of preoperative anaphylactic reactions to Neuro-Muscular Blocking Agents (NMBA) (114 patients analyzed at the BICHAT Hospital), a classical mechanism (mast cell- and IgE-dependent) is not identified. The mechanisms underlying these atypical anaphylactic reactions are unknown. The investigators have developed at the Pasteur Institute a murine model of anaphylaxis in which neutrophils, IgG and Platelet Activating Factor (PAF) play predominant roles. In addition, preliminary results obtained at the BICHAT Hospital suggest the presence of specific IgG anti-quaternary ammonium in the sera of patients that had developed a shock to NMBA anesthesia, but not in controls exposed to NMBA anesthesia or in normal blood donors. Finally, the release of neutrophil extracellular traps (NETs), extracellular filaments made of DNA and histones, may contribute to respiratory symptoms HYPOTHESIS: Neutrophils are implicated in NMBA -induced anaphylactic reactions in humans. Activated by IgG-NMBA complexes, which aggregate IgG receptors, neutrophils release PAF and NETs that are implicated in the cardiac and respiratory distress during anaphylaxis. It is possible that the activation of neutrophils: 1) explains the clinical features of atypical anaphylactic reactions (non-IgE mediated), 2) participates also in part to classical anaphylactic reactions GENERAL OBJECTIVE: Compare the percentage of circulating activated neutrophils in a group of patients immediately following a NMBA -induced shock (case) to that of a group of patients exposed to NMBA during anesthesia without developing a shock (control).

SECONDARY OBJECTIVES:

A) the day of the shock, quantify and compare between case and controls, 1) the level of circulating anti-quaternary ammonium IgG by immuno fluorometry, 2) the expression of IgG receptors (FcR) on the surface of neutrophils by cytometry, 3) the levels of circulating PAF by mass spectrometry, 4) the amount of NETs by immunofluorescence.

B) 6 to 10 weeks after the shock perform, 1) cutaneous tests to NMBA, 2) a study of the capacity of stimulation of ex vivo neutrophils by IgG- NMBA complexes


Condition Intervention
Anaphylactic Shock to Neuro-Muscular Blocking Agents (NMBA) Biological: Blood volume collected specifically for this study

Study Type: Observational
Study Design: Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Role of Neutrophil Activation in Anaphylaxis to Neuro-Muscular Blocking Agents

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Percentage of circulating activated neutrophils in the group case compared to that of the group of control. [ Time Frame: 30min post-anaphylactic shock ]
    This measure will be based on the intensity of expression of the activation marker CD62L (L-selectin) by blood neutrophils using flow cytometry. Our preliminary data indicate that the Mean Fluorescence Intensity (MFI) of CD62L is >450 when considering " non-activated " neutrophils, and CD62L(MFI)<300 when considering " activated " neutrophils.


Secondary Outcome Measures:
  • Levels of anti-quaternary ammonium specific IgG in the plasma [ Time Frame: 30min post-anaphylactic shock ]
    the group case compared to the group of control.

  • Ex vivo activation capacity of blood neutrophils in the presence of neuromuscular blocking drug-IgG immune complexes [ Time Frame: 30min post-anaphylactic shock ]
    the group case compared to the group of control.

  • Presence of Neutrophil Extracellular Traps in the bronchial aspiration fluid of "cases" [ Time Frame: 30min post-anaphylactic shock ]
    the group case compared to the group of control.


Enrollment: 200
Study Start Date: August 2012
Study Completion Date: December 2015
Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
case, control
Blood volume collected specifically for this study
Biological: Blood volume collected specifically for this study
  • case patient: 10 ml after the anaphylactic reaction, and during the Allergology-Anesthesia consult 6 to 8 weeks after the shock le choc.
  • Control patients: 20 ml following neuromuscular blocking drug injection

  Show Detailed Description

  Eligibility

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Selection of cases :

  • Any patient of age 18 and over:
  • Presenting with clinical signs compatible with a perioperative anaphylactic reaction to neuromuscular blocking drugs, whatever the grade of the anaphylactic reaction
  • That was treated following the French Patient Management 2011 guidelines

Selection of controls:

  • Any patient of age 18 and over
  • Hospitalized for a surgical intervention necessitating a neuromuscular blocking drug injection, without developing an anaphylactic reaction
  • That had been informed of the particulars of the study and that had consented to participate in this study
Criteria

Selection of cases :

INCLUSION CRITERIA:

  • Any patient of age 18 and over:
  • Presenting with clinical signs compatible with a perioperative anaphylactic reaction to neuromuscular blocking drugs, whatever the grade of the anaphylactic reaction
  • That was treated following the French Patient Management 2011 guidelines

EXCLUSION CRITERIA:

- pregnant women

Selection of controls:

INCLUSION CRITERIA :

  • Any patient of age 18 and over
  • Hospitalized for a surgical intervention necessitating a neuromuscular blocking drug injection, without developing an anaphylactic reaction
  • That had been informed of the particulars of the study and that had consented to participate in this study

EXCLUSION CRITERIA: none

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01637220


Locations
France
Hospital BICHAT
Paris, France, 75018
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Sylvie Chollet-Martin, MD-PhD Assistance Publique - Hôpitaux de Paris
  More Information

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01637220     History of Changes
Other Study ID Numbers: P110909
2012-A00242-41 ( Other Identifier: ID CRB )
First Submitted: June 4, 2012
First Posted: July 11, 2012
Last Update Posted: December 12, 2017
Last Verified: December 2017

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Anaphylaxis
Neutrophils
Platelet activating factor
Neutrophil Extracellular Traps (NETs)

Additional relevant MeSH terms:
Anaphylaxis
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Neuromuscular Blocking Agents
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs