<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03757052</url>
  </required_header>
  <id_info>
    <org_study_id>2019-4379</org_study_id>
    <nct_id>NCT03757052</nct_id>
  </id_info>
  <brief_title>Amoxicillin Challenge for Penicillin Allergy Diagnosis</brief_title>
  <acronym>Pen-VIE</acronym>
  <official_title>Safety, Validity and Efficiency of a Direct Graded Oral Challenge With Amoxicillin for the Evaluation of Penicillin Allergy in Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CHU de Quebec-Universite Laval</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>CHU de Quebec-Universite Laval</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      False diagnosis of penicillin allergy are frequently reported, and have been proven&#xD;
      detrimental to patients. Current guidelines for the assessment of drug allergies recommend&#xD;
      that penicillin allergy be evaluated first with prick and intradermal skin tests, and then&#xD;
      completed with a graded oral challenge, spread over at least two doses. However, it has been&#xD;
      shown that these skin tests, in addition to consuming resources and time, are of limited, or&#xD;
      even doubtful validity, given the poor predictive values that have been reported in the&#xD;
      modern penicillins era. It now seems unreasonable to continue their use without addressing&#xD;
      other, more efficient diagnostic stategies. Several groups have now demonstrated the safety,&#xD;
      validity, and efficiency of a direct, two-step amoxicillin oral challenge (starting with 10%&#xD;
      of the standard therapeutic dose, followed by 90 % of the dose), without prior skin tests,&#xD;
      first for any type of reaction in the pediatric population, then for any non-immediate&#xD;
      reaction in the adult population. The objective of this study is to demonstrate the safety,&#xD;
      efficiency, and validity of direct, two-step graded oral challenge with amoxicillin for the&#xD;
      evaluation of any reported penicillin allergy in the adult population, excluding high-risk&#xD;
      patients (documented anaphylaxis to a penicillin in the last 5 years). Skin tests will first&#xD;
      be performed according to the protocol currently in use at the CHUL, then consented patients&#xD;
      will proceed with the graded oral challenge still according to the protocol currently in use&#xD;
      at the CHUL, but regardless of the skin tests results. The results of the two tests will be&#xD;
      compared to determine the safety, efficiency and validity of proceeding directly to the&#xD;
      graded oral challenge.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 20, 2018</start_date>
  <completion_date type="Anticipated">June 2020</completion_date>
  <primary_completion_date type="Anticipated">April 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Type 1 Hypersensitivity Reaction</measure>
    <time_frame>60 minutes</time_frame>
    <description>The primary outcome is the occurrence of immediate hypersensitivity symptoms, occuring during the test period, which is up to 60 minutes after the last dose of amoxicillin.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Skin Tests Results</measure>
    <time_frame>60 minutes</time_frame>
    <description>Concordance of Skin Tests Results with Oral Challenge Results</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of immediate hypersensitivity symptoms</measure>
    <time_frame>60 minutes</time_frame>
    <description>Mild, moderate and severe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Delayed hypersensitivity symptoms</measure>
    <time_frame>14 days</time_frame>
    <description>Occurrence of delayed hypersensitivity symptoms</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">1000</enrollment>
  <condition>Penicillin Allergy</condition>
  <arm_group>
    <arm_group_label>Skin testing and Graded Oral Challenge</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Penicillin skin testing as described in the intervention section, followed by amoxicillin graded oral challenge as described in the intervention section</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Penicillin Skin Testing</intervention_name>
    <description>Skin test protocol: prick skin tests (penicilloyl-polylysine 0.000012 mol/0.05 mL, penicillin G 10,000 U/mL, penoate 10,000 U/mL, ampicillin 100 mg/mL, amoxicillin 71 mg/mL, histamine/positive control, diluent/negative control), then intradermal skin tests (penicilloyl-polylysine 0.000012 mol/0.05 mL, penicillin G 10,000 U/mL, penoate 10,000 U/mL, ampicillin 1 mg/mL, diluent/negative control), administered as an intradermal injection of a standardized volume of 0.02 mL. Graded oral challenge with amoxicillin : a first dose of 50 mg of amoxicillin; 20-minute observation period; in the absence of any objective symptom of an allergic reaction, a second dose of amoxicillin of 450 mg; final observation period of 60 minutes, under nurse and medical supervision.</description>
    <arm_group_label>Skin testing and Graded Oral Challenge</arm_group_label>
    <other_name>Amoxicillin Graded Oral Challenge</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Being 18 years of age or older at the time of the test&#xD;
&#xD;
          -  Being referred by a health professional for the evaluation of any allergic reaction to&#xD;
             a penicillin, including natural penicillins, anti-staphylococcal penicillins,&#xD;
             aminopenicillins, penicillins combined with a beta-lactamase inhibitor, and&#xD;
             carboxypenicillins ; or an antibiotic of the beta-lactam family, whose assessment&#xD;
             requires testing for penicillins, according to the treating allergist&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Poorly controlled asthma, chronic lung disease or heart disease&#xD;
&#xD;
          -  Failure to stop beta-blockers prior to the test&#xD;
&#xD;
          -  Occurrence of the reaction in the 4 weeks preceding the test (possibility of false&#xD;
             negatives)&#xD;
&#xD;
          -  History of severe delayed hypersensitivity reaction, reaction requiring&#xD;
             hospitalization of more than 24 hours, or bullous, pustular, exfoliative or mucosal&#xD;
             reaction (excluding angioedema)&#xD;
&#xD;
          -  Recent anaphylaxis (&lt;5 years), defined as concomitant involvement of at least two&#xD;
             systems (respiratory, digestive, mucocutaneous or cardiovascular) within one hour of&#xD;
             administration of the drug&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jean-Philippe Drolet, MD FRCPC</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU de Quebec-Universite Laval</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jean-Philippe Drolet, MD FRCPC</last_name>
    <phone>418-525-4444</phone>
    <email>jean-philippe.drolet@chudequebec.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Gaston De Serres, MD PhD</last_name>
    <phone>418-525-4444</phone>
    <email>Gaston.DeSerres@inspq.qc.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>CHU de Quebec</name>
      <address>
        <city>Quebec city</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jean-Philippe Drolet, MD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>November 22, 2018</study_first_submitted>
  <study_first_submitted_qc>November 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 28, 2018</study_first_posted>
  <last_update_submitted>March 13, 2019</last_update_submitted>
  <last_update_submitted_qc>March 13, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 14, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypersensitivity</mesh_term>
    <mesh_term>Drug Hypersensitivity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amoxicillin</mesh_term>
    <mesh_term>Penicillins</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03757052
org study id: 2019-4379
nct id: NCT03757052
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
False diagnosis of penicillin allergy are frequently reported, and have been proven
      detrimental to patients. Current guidelines for the assessment of drug allergies recommend
      that penicillin allergy be evaluated first with prick and intradermal skin tests, and then
      completed with a graded oral challenge, spread over at least two doses. However, it has been
      shown that these skin tests, in addition to consuming resources and time, are of limited, or
      even doubtful validity, given the poor predictive values that have been reported in the
      modern penicillins era. It now seems unreasonable to continue their use without addressing
      other, more efficient diagnostic stategies. Several groups have now demonstrated the safety,
      validity, and efficiency of a direct, two-step amoxicillin oral challenge (starting with 10%
      of the standard therapeutic dose, followed by 90 % of the dose), without prior skin tests,
      first for any type of reaction in the pediatric population, then for any non-immediate
      reaction in the adult population. The objective of this study is to demonstrate the safety,
      efficiency, and validity of direct, two-step graded oral challenge with amoxicillin for the
      evaluation of any reported penicillin allergy in the adult population, excluding high-risk
      patients (documented anaphylaxis to a penicillin in the last 5 years). Skin tests will first
      be performed according to the protocol currently in use at the CHUL, then consented patients
      will proceed with the graded oral challenge still according to the protocol currently in use
      at the CHUL, but regardless of the skin tests results. The results of the two tests will be
      compared to determine the safety, efficiency and validity of proceeding directly to the
      graded oral challenge.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Type 1 Hypersensitivity Reaction
time frame: 60 minutes
description: The primary outcome is the occurrence of immediate hypersensitivity symptoms, occuring during the test period, which is up to 60 minutes after the last dose of amoxicillin.
measure: Skin Tests Results
time frame: 60 minutes
description: Concordance of Skin Tests Results with Oral Challenge Results
measure: Severity of immediate hypersensitivity symptoms
time frame: 60 minutes
description: Mild, moderate and severe
measure: Delayed hypersensitivity symptoms
time frame: 14 days
description: Occurrence of delayed hypersensitivity symptoms
arm group label: Skin testing and Graded Oral Challenge
arm group type: Experimental
description: Penicillin skin testing as described in the intervention section, followed by amoxicillin graded oral challenge as described in the intervention section
intervention type: Diagnostic Test
intervention name: Penicillin Skin Testing
description: Skin test protocol: prick skin tests (penicilloyl-polylysine 0.000012 mol/0.05 mL, penicillin G 10,000 U/mL, penoate 10,000 U/mL, ampicillin 100 mg/mL, amoxicillin 71 mg/mL, histamine/positive control, diluent/negative control), then intradermal skin tests (penicilloyl-polylysine 0.000012 mol/0.05 mL, penicillin G 10,000 U/mL, penoate 10,000 U/mL, ampicillin 1 mg/mL, diluent/negative control), administered as an intradermal injection of a standardized volume of 0.02 mL. Graded oral challenge with amoxicillin : a first dose of 50 mg of amoxicillin; 20-minute observation period; in the absence of any objective symptom of an allergic reaction, a second dose of amoxicillin of 450 mg; final observation period of 60 minutes, under nurse and medical supervision.
arm group label: Skin testing and Graded Oral Challenge
other name: Amoxicillin Graded Oral Challenge
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Jean-Philippe Drolet, MD FRCPC
role: Principal Investigator
affiliation: CHU de Quebec-Universite Laval
last name: Jean-Philippe Drolet, MD FRCPC
phone: 418-525-4444
email: jean-philippe.drolet@chudequebec.ca
last name: Gaston De Serres, MD PhD
phone: 418-525-4444
email: Gaston.DeSerres@inspq.qc.ca
facility: 
status: Recruiting
contact: 
country: Canada
responsible party type: Sponsor
mesh term: Hypersensitivity
mesh term: Drug Hypersensitivity
mesh term: Amoxicillin
mesh term: Penicillins
sharing ipd: Undecided