Genomic Study of Genetic Polymorphisms Involved in Immediate Allergic Reactions to Beta-lactam Antibiotics

• Conditions: Beta-Lactams Allergy; Hypersensitivity
• Interventions: Other: Collection of blood sample

• Registration Number: NCT02895646
• Lead Sponsor: Central Hospital, Nancy, France

Brief Summary

Beta-lactam antibiotics include penicillin and cephalosporins and are among the most prescribed antibiotics. This category of drugs is the most involved in immediate allergic manifestations with 2% reactions in treated subjects and a fatal outcome in 1/50000 treatments. Reactions are IgE-mediated and have a considerable but unknown genetic origin, revealed by studies in groups of different ethnical origins in the same geographical region. There are also some families with a high frequency of allergic reactions without identified Mendelian inheritance.

The purpose of this study is to identify predictive risk factors associated to immediate allergic reactions against beta-lactam antibiotics with a pangenomic approach.

A secondary purpose is to identify rare predictive factors with homozygosity mapping and exome sequencing in various families with high risk of allergy to beta-lactam antibiotics.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-06
• Status Verified: 2016-09
• Study First Submitted: 2016-09-05
• Study First Submitted QC: 2016-09-09
• Study First Posted: 2016-09-12
• Last Update Submitted: 2017-02-02
• Last Update Posted: 2017-02-03
• Primary Completion: 2017-06
• Study Completion: 2017-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 2356

Inclusion Criteria

• Informed consent
• Allergy group: Immediate allergic reaction (less than 2 hours after drug administration) to an antibiotic of penicillin or cephalosporin groups
• Allergy group: Positive skin test (intradermal test) with a non-irritant dilution of antibiotic of penicillin or cephalosporin groups

Exclusion Criteria

• Refusal of participation

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Beta-lactam antibiotic allergy	Collection of blood sample	Diagnosis based on clinical symptomatology and skin test positive for allergen and negative for other drugs and substances. Skin tests are performed 6 weeks after allergic reaction.
Control	Collection of blood sample	No specific clinical investigation for control subjects

Primary Outcome Measures

Name	Time	Method
Analysis of genetic polymorphisms predictive of risk of beta-lactam immediate allergy	day 0	Common (\>10%) or rare (1-10%) genetic polymorphisms in patients with beta-lactam immediate allergy

Secondary Outcome Measures

Name	Time	Method
Reactivity to skin test	day 0
Severity of allergic reaction	day 0	evaluated during clinical examination
Analysis of allelic homozygosity linked to allergen response, in more than 2 allergic individuals of the same family	day 0	Allelic homozygosity in one or more regions of genome with one or more genes involved in allergen response, in more than 2 individuals affected by beta-lactam allergy in the same family
Serum concentration of specific IgE	day 0