Amoxicillin Challenge for Penicillin Allergy Diagnosis

NCT ID: NCT03757052

Last Updated: 2019-03-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 1000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-20
• Study Completion Date: 2020-06-30

Brief Summary

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.

Conditions

Penicillin Allergy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Skin testing and Graded Oral Challenge

Penicillin skin testing as described in the intervention section, followed by amoxicillin graded oral challenge as described in the intervention section

Group Type: EXPERIMENTAL

Penicillin Skin Testing

Intervention Type: DIAGNOSTIC_TEST

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.

Interventions

Penicillin Skin Testing

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.

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

Amoxicillin Graded Oral Challenge

Eligibility Criteria

Inclusion Criteria

• Being 18 years of age or older at the time of the test
• Being referred by a health professional for the evaluation of any allergic reaction to a penicillin, including natural penicillins, anti-staphylococcal penicillins, aminopenicillins, penicillins combined with a beta-lactamase inhibitor, and carboxypenicillins ; or an antibiotic of the beta-lactam family, whose assessment requires testing for penicillins, according to the treating allergist

Exclusion Criteria

• Pregnancy
• Poorly controlled asthma, chronic lung disease or heart disease
• Failure to stop beta-blockers prior to the test
• Occurrence of the reaction in the 4 weeks preceding the test (possibility of false negatives)
• History of severe delayed hypersensitivity reaction, reaction requiring hospitalization of more than 24 hours, or bullous, pustular, exfoliative or mucosal reaction (excluding angioedema)
• Recent anaphylaxis (<5 years), defined as concomitant involvement of at least two systems (respiratory, digestive, mucocutaneous or cardiovascular) within one hour of administration of the drug

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

CHU de Quebec-Universite Laval

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Philippe Drolet, MD FRCPC

Role: PRINCIPAL_INVESTIGATOR

CHU de Quebec-Universite Laval

Locations

CHU de Quebec

Québec, Quebec, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Jean-Philippe Drolet, MD FRCPC

Role: CONTACT

jean-philippe.drolet@chudequebec.ca

418-525-4444

Gaston De Serres, MD PhD

Role: CONTACT

Gaston.DeSerres@inspq.qc.ca

418-525-4444

Facility Contacts

Jean-Philippe Drolet, MD

Role: primary

Other Identifiers

2019-4379

Identifier Type: -

Identifier Source: org_study_id