Allergy to Neuromuscular Blocking Agents and Pholcodine Exposure

NCT02250729 | Unknown DMC

• 1 other identifier: 2012-A01735-38
• Study Type: interventional
• Target: 1,020
• Locations: 1 country
• Sites: 24

Brief Summary

The main objective of this study is to compare pholcodine exposure in patients having presented with a perianaesthetic anaphylactic reaction to a NMBA (cases) to pholcodine exposure in matched anaesthetised patients with injection of NMBA, who did not present with an anaphylactic reaction (controls). The secondary objectives of the study are:

• To compare anti-pholcodine IgE, anti-ammonium IV IgE and total IgE levels between the case and control groups.
• To study the concordance between exposure to pholcodine in cases and controls, by means of a patient self-questionnaire on the one hand and, on the other hand, by a computerized drug history, supplemented where relevant by the drug master file.
• To study the impact of taking 1, 2 or 3 sources in account for pholcodine exposition.
• To study the association between exposure to pholcodine and the presence/levels of pholcodine-specific IgE, reflecting sensitisation to pholcodine.
• To study NMBA and pholcodine cross-sensitisation by testing skin reactions to pholcodine in case patients allergic to (at least) one NMBA.

Conditions

Neuromuscular Blocking Agents Anaphylaxis

Keywords

anaphylaxis; pholcodine; neuromuscular blocking agents

Outcome Measures

Primary Outcomes (1)

• Exposure to pholcodine

  Exposure is measured by autoquestionnaire, patient's pharmaceutical file and drug history by the pharmacist's

  within the 12 months before the anesthetic procedure

Secondary Outcomes (5)

• Anti-pholcodine IgE, anti-ammonium IV IgE and total IgE levels between the case and control groups.

  Between 1 day to 12 weeks after the general anesthetic procedure

• Concordance between exposure to pholcodine in cases and controls, by means of a patient self-questionnaire on the one hand and, on the other hand, by a computerized drug history, supplemented where relevant by the drug master file.

  within the 12 months preceeding the general anesthesia

• Impact of non subjective sources in pholcodine exposure assessment

  within the 12 months preceeding general anesthetic procedure

• Association between exposure to pholcodine and the presence/levels of pholcodine-specific IgE, reflecting sensitisation to pholcodine.

  within the 12 months preceding the general anesthetic procedure

• NMBA and pholcodine cross-sensitisation by testing skin reactions to pholcodine in case patients allergic to one NMBA.

  6 to 12 weeks after the general anesthetic procedure

Study Arms (2)

cases with NMBA anaphylaxis

EXPERIMENTAL

Patients who experienced NMBA anaphylaxis during anesthesia

Other: intradermal pholcodine allergy test in cases; Other: Blood sampling

controls

OTHER

Patients who underwent anesthesia with NMBA injection but did not experience anaphylaxis

Other: Blood sampling

Interventions

intradermal pholcodine allergy test in cases OTHER

cases with NMBA anaphylaxis

Blood sampling OTHER

cases with NMBA anaphylaxis; controls

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age ≥ 2 years old.
• Referred to anaesthesia-allergy consultation within (approximately) 6 to 12 weeks of occurrence of peranaesthetic anaphylactic reaction during anaesthesia with administration of NMBAs (only for case patient).
• Having given his/her consent (or the 2 parents consent for minors).
• Affiliated with a social security scheme or dependent.
• Able to answer a medicinal product intake questionnaire
• In a clinical condition compatible with skin tests (no skin disease or psychiatric illness, etc.) (only for case patient)
• Having stopped any anti-histamine treatment at least 8 days previously (only for case patient).
• With positive skin test for the suspected NMBA (ony for case patient).
• Patient anaesthetised in a control recruitment centre (only for control patients)
• Having undergone anaesthesia with NMBA injection, without onset of peranaesthetic anaphylactic reaction whatever his medical history (only for control patients)

You may not qualify if:

• Patients who have refused, or are unable to give their consent
• Patients who have had negative control skin tests
• Anaphylaxis suspected to be related to other drugs given on induction of anaesthesia, eg. antibiotics
• Having presented with anaphylactic reaction during a previous anaesthesia without NMBA injection

Sponsors & Collaborators

• Central Hospital, Nancy, France: lead
• Zambon SpA: collaborator
• Laboratoires URGO: collaborator
• THE BOOTS COMPANY PLC: collaborator
• Pierre Fabre Medicament: collaborator
• LABORATOIRE HEPATOUM: collaborator
• Biocodex: collaborator
• Sanofi: collaborator
• RECORDATI GROUP: collaborator
• GlaxoSmithKline: collaborator
• ALLIANCE PHARMACEUTICALS LIMITED: collaborator
• BELL SONS & COMPANY: collaborator
• PINEWOOD LABORATORIES LIMITED: collaborator
• THORNTON & ROSS & Ross Ltd: collaborator
• ERNEST JACKSON & Co. Ltd: collaborator

Study Sites (24)

CHU d' ANGERS

Angers, France

RECRUITING

CHU de Besançon

Besançon, 25030, France

NOT YET RECRUITING

CHU de Bordeaux

Bordeaux, 33000, France

RECRUITING

CHU de Caen

Caen, 14000, France

RECRUITING

CHU de Clermont-Ferrand

Clermont-Ferrand, 63003, France

RECRUITING

CHU de Dijon

Dijon, 21033, France

RECRUITING

CHRU de Lille

Lille, 59037, France

RECRUITING

CHU de Limoges

Limoges, 87042, France

RECRUITING

AP-HM

Marseille, 13915, France

NOT YET RECRUITING

CHU de MONTPELLIER

Montpellier, 34000, France

RECRUITING

CHRU de Nancy

Nancy, 54000, France

RECRUITING

CHU de NANTES

Nantes, France

RECRUITING

CHU de Nice

Nice, 06000, France

RECRUITING

Fondation Hôpital St Joseph

Paris, 75007, France

RECRUITING

AP-HP- Hôpital Bichat

Paris, 75877, France

RECRUITING

AP-HP Paris TENON

Paris, France

RECRUITING

Hospices Civils de Lyon

Pierre-Bénite, 69495, France

RECRUITING

CHU de Poitiers

Poitiers, 86000, France

RECRUITING

CHU de Reims

Reims, 51100, France

RECRUITING

CHU de Rouen

Rouen, 76000, France

RECRUITING

CHU de Saint Etienne

Saint-Etienne, 42055, France

RECRUITING

CHU de Strasbourg

Strasbourg, 670000, France

RECRUITING

CHU de Toulouse

Toulouse, 31059, France

RECRUITING

CHU de TOURS

Tours, France

RECRUITING

Related Publications (1)

• Mertes PM, Petitpain N, Tacquard C, Delpuech M, Baumann C, Malinovsky JM, Longrois D, Gouel-Cheron A, Le Quang D, Demoly P, Gueant JL, Gillet P; ALPHO Study Group. Pholcodine exposure increases the risk of perioperative anaphylaxis to neuromuscular blocking agents: the ALPHO case-control study. Br J Anaesth. 2023 Jul;131(1):150-158. doi: 10.1016/j.bja.2023.02.026. Epub 2023 Mar 24.

  PMID: 36967281 DERIVED

MeSH Terms

Conditions

Anaphylaxis

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Pierre GILLET, PU-PH MD

  Central Hospital, Nancy, France

  PRINCIPAL INVESTIGATOR

• Paul-Michel MERTES, PU-PH MD

  CHU de Strasbourg

  STUDY DIRECTOR

Central Study Contacts

Pierre Gillet, MD PhD

CONTACT

pierre.gillet@univ.lorraine.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2014
• First Posted: September 26, 2014
• Study Start: July 1, 2014
• Primary Completion: July 1, 2020
• Study Completion: July 1, 2020
• Last Updated: December 27, 2018

Record last verified: 2018-12

Locations

FR (24)