Neuromuscular Blocking Agents AnaphylaxisALPHONCT02250729
Allergy to Neuromuscular Blocking Agents and Pholcodine Exposure
A study testing intradermal pholcodine allergy test in cases and Blood sampling in people with Neuromuscular Blocking Agents Anaphylaxis, run by Central Hospital, Nancy, France at 24 sites in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Neuromuscular Blocking Agents Anaphylaxis
- What is being tested?
- intradermal pholcodine allergy test in cases and Blood sampling
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,020 participants
- Where
- 24 sitesFrance
- Study dates
- Jul 2014to Jul 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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)
Show all 10Show fewer
- 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)
Who cannot join
- 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
- Pregnant females at inclusion or during 12 months before anaesthesia
Trial locations and contacts
24 sites in 1 country.
Pierre Gillet, MD PhD contact
24 sites in 1 country
France24 sites, 24 recruiting
- Recruiting
CHU d' ANGERS
Angers
Martine DROUET, Dr
- Not yet recruiting
CHU de Besançon
Besançon, 25030
Pascal GIRARDIN, MD, pgirardin@chu-besancon.fr
- Recruiting
CHU de Bordeaux
Bordeaux, 33000
Maryline Bordes, maryline.bordes@chu-bordeaux.fr
- Recruiting
CHU de Caen
Caen, 14000
Delphine MARIOTTEFAUSSART, MD, mariotte-d@chu-caen.fr
- Recruiting
CHU de Clermont-Ferrand
Clermont-Ferrand, 63003
Omar OUTTAS, MD, oouttas@chu-clermontferrand.fr;
- Recruiting
CHU de Dijon
Dijon, 21033
Sandrine SELTZER, MD, sandrine.seltzer@chu-dijon.fr
- Recruiting
CHRU de Lille
Lille, 59037
FACON Alain, MD, alain.facon@chru-lille.fr
- Recruiting
CHU de Limoges
Limoges, 87042
Isabelle ORSEL, MD, isabelle.orsel@chu-limoges.fr
- Not yet recruiting
AP-HM
Marseille, 13915
Marion GOUITAA-DETTORI, MD, marion.gouitaa@ap-hm.fr
- Recruiting
CHU de MONTPELLIER
Montpellier, 34000
Pascal DEMOLY, Pr
- Recruiting
CHRU de Nancy
Nancy, 54000
Gérard AUDIBERT, MD-PHD, g.audibert@chu-nancy.fr
- Recruiting
CHU de NANTES
Nantes
ANAIS PIPET, Dr
- Recruiting
CHU de Nice
Nice, 06000
Sylvie LEROY, MD, leroy.s2@chu-nice.fr
- Recruiting
Fondation Hôpital St Joseph
Paris, 75007
Marie-Laure MEGRET-GABEAUD, Dr
- Recruiting
AP-HP- Hôpital Bichat
Paris, 75877
Dan LONGROIS, MD- PHD, dan.longrois@bch.aphp.fr
- Recruiting
AP-HP Paris TENON
Paris
ANGELE SORIA, Dr
- Recruiting
Hospices Civils de Lyon
Pierre-Bénite, 69495
Vincent PIRIOU, MD, vincent.piriou@chu-lyon.fr
- Recruiting
CHU de Poitiers
Poitiers, 86000
Marion VERDAGUER, MD, marion.verdaguer@chu-poitiers.fr
- Recruiting
CHU de Reims
Reims, 51100
Jean-Marc MALINVOSKY, MD-PHD, jmmalinovsky@chu-reims.fr
- Recruiting
CHU de Rouen
Rouen, 76000
Yannick MEUNIER, MD, yannick.meunier@chu-rouen.fr
- Recruiting
CHU de Saint Etienne
Saint-Etienne, 42055
Charles DZVIGA, MD, c.dzviga@magic.fr
- Recruiting
CHU de Strasbourg
Strasbourg, 670000
Fréderic DE BLAY, MD- PHD, frederic.deblay@chru-strasbourg.fr
Paul-Michel Mertes, MD- PHD, paul-michel.mertes@chru-strasbourg.fr
- Recruiting
CHU de Toulouse
Toulouse, 31059
Alain DIDIER, MD-PHD, didier.a@chu-toulouse.fr
- Recruiting
CHU de TOURS
Tours
Cyrille HOARAU, Dr
About this study
Official title: Anaphylaxis to Neuromuscular Blocking Agents and Pholcodine Exposure. Case-control Study
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.
- Being tested
- intradermal pholcodine allergy test in cases, Blood sampling
- Keywords
- anaphylaxis, pholcodine, neuromuscular blocking agents
- Medical subject headings
- Anaphylaxis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
intradermal pholcodine allergy test in casesOther
Blood samplingOther
| Study group | Role | What they receive |
|---|---|---|
| cases with NMBA anaphylaxis | Experimental | Patients who experienced NMBA anaphylaxis during anesthesia Receives: Other: intradermal pholcodine allergy test in cases; Other: Blood sampling |
| controls | Other | Patients who underwent anesthesia with NMBA injection but did not experience anaphylaxis Receives: Other: Blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Exposure to pholcodine
Exposure is measured by autoquestionnaire, patient's pharmaceutical file and drug history by the pharmacist's
Measured: 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.
Cases: 6 to 12 weeks after the general anesthetic procedure (corresponding to the day of inclusion) Controls: during their hospitalisation after the general anesthetic procedure (Maximum 90 days after the general anesthetic procedure, corresponding to the day of inclusion)
Measured: 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.
Measured: within the 12 months preceeding the general anesthesia
Impact of non subjective sources in pholcodine exposure assessment
We will study if pholcodine exposure criteria measured by autoquestionnaire is modified by taking into account non subjectives sources which are the patient's pharmaceutical file and his drug history by his pharmacist's
Measured: 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.
IgE measurements: total IgE, IgE specific for pholcodine, quaternary ammoniums (KU/L)
Measured: 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.
Only for Cases :
Intradermal tests with diluted pholcodine. Intradermal tests with diluted NMBAs (as usual)
Measured: 6 to 12 weeks after the general anesthetic procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2014 (estimated)
- Study startJul 2014
- Primary completionJul 2020 (estimated)
- Study completionJul 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neuromuscular Blocking Agents AnaphylaxisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,020 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Central Hospital, Nancy, France
- Sponsor type
- University, hospital or other
- Collaborators
- Zambon SpA, Laboratoires URGO, THE BOOTS COMPANY PLC, Pierre Fabre Medicament, LABORATOIRE HEPATOUM, Biocodex, Sanofi, RECORDATI GROUP, GlaxoSmithKline, ALLIANCE PHARMACEUTICALS LIMITED, BELL SONS & COMPANY, PINEWOOD LABORATORIES LIMITED, THORNTON & ROSS & Ross Ltd, ERNEST JACKSON & Co. Ltd
- Responsible party
- Sponsor
- Investigators
- Pierre GILLET, PU-PH MD, Principal investigator, Central Hospital, Nancy, FrancePaul-Michel MERTES, PU-PH MD, Study director, CHU de Strasbourg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02250729
- Sponsor's protocol ID
- 2012-A01735-38
- Acronym
- ALPHO
- Status last verified
- Dec 2018
- First submitted
- 12 May 2014
- Last updated
- 27 Dec 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 36967281
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anaphylaxis to Neuromuscular Blocking Agents and Pholcodine Exposure. Case-control Study
- ClinicalTrials.gov ID
- NCT02250729
- Acronym / sponsor ID
- ALPHO / 2012-A01735-38
- Keywords
- anaphylaxis, pholcodine, neuromuscular blocking agents
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,020 participants (estimated)
- Lead sponsor
- Central Hospital, Nancy, FranceUniversity, hospital or other
- Collaborators
- Zambon SpA, Laboratoires URGO, THE BOOTS COMPANY PLC, Pierre Fabre Medicament, LABORATOIRE HEPATOUM, Biocodex, Sanofi, RECORDATI GROUP, GlaxoSmithKline, ALLIANCE PHARMACEUTICALS LIMITED, BELL SONS & COMPANY, PINEWOOD LABORATORIES LIMITED, THORNTON & ROSS & Ross Ltd, ERNEST JACKSON & Co. Ltd
- Study start
- Jul 2014 (actual)
- Primary completion
- Jul 2020 (estimated)
- Study completion
- Jul 2020 (estimated)
- First posted
- 26 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| cases with NMBA anaphylaxis | Experimental | Other: intradermal pholcodine allergy test in cases, Other: Blood samplingPatients who experienced NMBA anaphylaxis during anesthesia |
| controls | Other | Other: Blood samplingPatients who underwent anesthesia with NMBA injection but did not experience anaphylaxis |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (5 listed)
- 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
- Pregnant females at inclusion or during 12 months before anaesthesia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| intradermal pholcodine allergy test in cases | Other | cases with NMBA anaphylaxis |
| Blood sampling | Other | cases with NMBA anaphylaxis, controls |
Primary outcome
Exposure to pholcodine
Time frame: within the 12 months before the anesthetic procedure
Exposure is measured by autoquestionnaire, patient's pharmaceutical file and drug history by the pharmacist's
5 secondary outcomes
Anti-pholcodine IgE, anti-ammonium IV IgE and total IgE levels between the case and control groups.
Time frame: 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.
Time frame: within the 12 months preceeding the general anesthesia
Impact of non subjective sources in pholcodine exposure assessment
Time frame: 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.
Time frame: 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.
Time frame: 6 to 12 weeks after the general anesthetic procedure
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2018.
- Derived from this study: PubMed 36967281Mertes 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pierre Gillet, MD PhD contact
Pierre GILLET, PU-PH MD principal investigator
Central Hospital, Nancy, France
Paul-Michel MERTES, PU-PH MD study director
CHU de Strasbourg
24 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing intradermal pholcodine allergy test in cases and Blood sampling in people with Neuromuscular Blocking Agents Anaphylaxis, run by Central Hospital, Nancy, France at 24 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Pierre Gillet, MD PhD (pierre.gillet@univ.lorraine.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Exposure to pholcodine (time frame: within the 12 months before the anesthetic procedure). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02250729, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2018.