Diagnosing Drug Allergy: the T is the Key (TAT)

Diagnosing Drug Allergy the T is the Key

The goal of this clinical trial is to validate a newly developed test in the diagnosis of patients with amoxicillin allergy (i.e. T-cell activation test). The main questions the study aims to assess are the reliability and applicability of this test. Participants will be asked to visit the hospital 1, 3 or 5 times during which blood is collected and when applicable, allergy skin testing is performed.

Study Overview

• Status: Not yet recruiting
• Conditions: Amoxicillin Allergy
• Intervention / Treatment: Device: T-cell activation test using intracellular markers

Detailed Description

Drug allergy is a significant health issue with a serious medical and financial burden of mis- and overdiagnosis. Currently applied tests differ for immediate and nonimmediate drug allergy and have variable sensitivity and specificity. Therefore, correct diagnosis remains difficult and frequently requires potentially dangerous and time-consuming challenge tests. Drug-specific T-cells play a central role in initiation and maintenance of both immediate and nonimmediate drug allergy and can be studied in the lymphocyte transformation test (LTT). However, technical difficulties have hindered entrance of the LTT in mainstream use. The investigators' data indicates that flow-based intracellular trapping and staining of markers induced during activation (such as CD154 and cytokines) enables a rapid enumeration of rare drug-specific T-cells in the blood of patients with immediate and nonimmediate amoxicillin allergy. The ambition of this project is to validate a "one fits all" assay that meets the requirements of a safe, patient friendly, accessible, and performant test that could merits the status of a primary investigation in the diagnostic algorithms. Moreover, as the tests is cost effective, it could also become an attractive method for broader applications such as the delabelling of spurious allergies. This project will focus on allergy to amoxicillin.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Didier Ebo, PhD; Phone Number: +3238213526; Email: Didier.Ebo@uza.be
• Study Contact Backup: Name: Caro Verberckt, Msc; Phone Number: +3238215027; Email: studies.immunologie@uza.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Participants are eligible if they:

• Are ≥ 6 years
• Are capable of informed consent, or if appropriate, participants have an acceptable individual capable of giving consent on the participant's behalf (e.g. parent or guardian of a child under 18 years of age)
• Have a suspected history of amoxicillin allergy

Exclusion Criteria:

• Patients who are lacking capacity or do not have an acceptable individual capable to provide informed consent
• Pregnant women
• Breastfeeding women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with a suspected amoxicillin allergy; Patients with a suspected amoxicillin allergy for which the diagnostic work-up was performed at the hospital for the possible diagnosis of amoxicillin allergy.	Device: T-cell activation test using intracellular markers; A blood sample will be taken which is needed for the T-cell activation test (TAT). The TAT will than be performed by trained laboratory personnel.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity and specificity of the T-cell activation test	Sensitivity and specificity of the T-cell activation test during Study Visit 1 of patients with amoxicillin allergy and control subjects without amoxicillin allergy.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive predictive value (PPV) and negative predictive value (NPV), accuracy and likelihood ratio (LR)	Positive predictive value (PPV) and negative predictive value (NPV), accuracy and likelihood ratio (LR) of the T-cell activation test in the diagnosis of amoxicillin allergy.	Baseline
Percentage of cases with a positive TAT and positive IgE and/or skin test	Percentage of cases with a positive TAT and positive IgE and/or skin test	Baseline
Association between the severity of the index reaction and the performance of TAT in terms of odds ratio.	The impact of severity of the index reaction on TAT-positivity will be studied in a logistic regression model. Odds ratios and 95% confidence intervals will be reported.	Baseline
Association between the time since the index reaction and the performance of TAT in terms of odds ratio.	The impact of the time since the index reaction on TAT-positivity will be studied in a logistic regression model. Odds ratios and 95% confidence intervals will be reported.	Basline
Association between IDHR/non-IDHR and the performance of TAT in terms of odds ratio.	The impact of IDHR/non-IDHR on TAT-positivity will be studied in a logistic regression model. Odds ratios and 95% confidence intervals will be reported.	Baseline
Association between the severity of the index reaction and the net percentage of intracellular T-cell activation marker CD154.	The impact of severity of the index reaction on the individual components of TAT will be studied in linear regression models, with respectively net percentage of intracellular T-cell activation markers CD154 as dependent variable. Unstandardized and standardized coefficients and standard errors will be reported.	Baseline
Association between the severity of the index reaction and the net percentage of intracellular T-cell activation marker IL-4.	The impact of severity of the index reaction on the individual components of TAT will be studied in linear regression models, with respectively net percentage of intracellular T-cell activation markers IL-4 as dependent variable. Unstandardized and standardized coefficients and standard errors will be reported.	Baseline
Association between the severity of the index reaction and the net percentage of cytokine IFN-γ.	The impact of severity of the index reaction on the individual components of TAT will be studied in linear regression models, with respectively net percentage of intracellular T-cell activation markers IFN-γ as dependent variable. Unstandardized and standardized coefficients and standard errors will be reported.	Baseline
Association between the time since the index reaction and the net percentage of intracellular T-cell activation marker CD154.	The impact of the time since the index reaction on the individual components of TAT will be studied in linear regression models, with respectively net percentage of intracellular T-cell activation markers CD154 as dependent variable. Unstandardized and standardized coefficients and standard errors will be reported.	Baseline
Association between the time since the index reaction and the net percentage of intracellular T-cell activation marker IL-4.	The impact of the time since the index reaction on the individual components of TAT will be studied in linear regression models, with respectively net percentage of intracellular T-cell activation markers IL-4 as dependent variable. Unstandardized and standardized coefficients and standard errors will be reported.	Baseline
Association between the time since the index reaction and the net percentage of cytokine IFN-γ.	The impact of time since the index reaction on the individual components of TAT will be studied in linear regression models, with respectively net percentage of intracellular T-cell activation markers IFN-γ as dependent variable. Unstandardized and standardized coefficients and standard errors will be reported.	Baseline
Association between IDHR / non-IDHR and the net percentage of intracellular T-cell activation marker CD154.	The impact of IDHR / non-IDHR on the individual components of TAT will be studied in linear regression models, with respectively net percentage of intracellular T-cell activation markers CD154 as dependent variable. Unstandardized and standardized coefficients and standard errors will be reported.	Baseline
Association between IDHR / non-IDHR and the net percentage of intracellular T-cell activation marker IL-4.	The impact of IDHR / non-IDHR on the individual components of TAT will be studied in linear regression models, with respectively net percentage of intracellular T-cell activation markers IL-4 as dependent variable. Unstandardized and standardized coefficients and standard errors will be reported.	Baseline
Association between IDHR / non-IDHR and the net percentage of cytokine IFN-γ.	The impact of IDHR / non-IDHR on the individual components of TAT will be studied in linear regression models, with respectively net percentage of intracellular T-cell activation markers IFN-γ as dependent variable. Unstandardized and standardized coefficients and standard errors will be reported.	Baseline
Sensitivity and specificity of TAT in subgroup of cases and controls with immediate and nonimmediate reactors	Sensitivity and specificity of T-cell activation test in a subgroup of cases and controls with immediate and nonimmediate reactors	Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of TAT 1 year and 3 years after diagnosis	Sensitivity of TAT 1 year and 3 years after diagnosis of patients with amoxicillin allergy	After 1 and 3 years
Evolution TAT-components over time	Evolution TAT-components over time in patients with amoxicillin allergy	After 1 and 3 years

Collaborators and Investigators

• Sponsor: University Hospital, Antwerp
• Collaborators: Universiteit Antwerpen; AZ Jan Palfijn Gent
• Investigators: Principal Investigator: Didier Ebo, PhD, University Hospital, Antwerp

Study record dates

Study Major Dates

• Study Start (Estimated): May 25, 2024
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: April 17, 2024
• First Submitted That Met QC Criteria: May 7, 2024
• First Posted (Actual): May 10, 2024

Study Record Updates

• Last Update Posted (Actual): May 10, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Allergy; T-cells; Amoxicillin; Amoxicillin Allergy
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Immune System Diseases; Drug-Related Side Effects and Adverse Reactions; Hypersensitivity; Drug Hypersensitivity
• Other Study ID Numbers: 003220

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No