HLA Screening in Reducing the Risk of Antiepileptic Drug-induced Cutaneous Adverse Reactions

HLA Screening in Reducing the Risk of Antiepileptic Drug-induced Cutaneous Adverse Reactions: a Multicenter Clinical Study

Cutaneous adverse drug reactions (cADRs) include mild maculopapular exanthema (MPE) and severe cutaneous reactions such as hypersensitivity syndrome, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). cADRs are considered as a major public health issue because of their potentially life-threatening morbidity, especially severe cutaneous reactions. The incidence of SJS/TEN is estimated to vary from 1 in 1,000 to 10,000 drug exposures, and its mortality is as high as 35%. Antiepileptic drugs (AEDs), particularly those with aromatic ring structures such as carbamazepine (CBZ), oxcarbazepine (OXC), lamotrigine (LTG), phenobarbital (PB), and phenytoin (PHT), are among the most common causes of severe cutaneous reactions. The incidence of AED-induced SJS was estimated as 0.2% and all cases occurred in individuals receiving aromatic AEDs.

Previous studies have validated that the human leukocyte antigen (HLA) allele HLA-B*15:02 is strongly associated with CBZ-induced SJS/TEN in southern Han Chinese and populations in southeast Asia. Our recent studies indicated that HLA-A*24:02 is a common genetic risk factor for CBZ-, LTG-, and PHT-induced SJS/TEN. It is also associated with MPE. Additionally, another four alleles, including HLA-B*15:01, HLA-B*15:11, HLA-A*02:01,and HLA-DRB1*01:01, were showed to be potential risk factors for aromatic AEDs-induced SJS/TEN. In 2007, the US Food and Drug Administration issued the safety alert that recommended HLA-B*15:02 screening for people with Asian ancestry before starting CBZ, and avoidance of the drug if the test is positive. Subsequent studies from Taiwan, Hong Kong and Thailand demonstrated that HLA-B*15:02 screening before commencing CBZ can significantly reduce the incidence of CBZ-induced SJS/TEN. However, the overall incidence of AEDs-induced SJS/TEN remained unchanged in Hong Kong, as PHT-induced SJS/TEN increased when CBZ-SJS/TEN decreased. Moreover, no study focuses on the incidences of AEDs-induced cADRs with and without HLA screening before commencing aromatic AEDs. Therefore, we are planning to conduct a multicenter prospective study to examine the reduction of AEDs-induced cADRs after the HLA screening prior to the beginning of aromatic AEDs administration.

Study Overview

Detailed Description

In this prospective study, 4000 or more patients from multicenters in southern China will be recruited. A HLA screening will be conducted before these patients start aromatic AEDs treatments. According to the HLA genotype, these patients will be divided into four groups that are three positive groups with different risk alleles and one negative group with no known risk allele. Aromatic AEDs were avoided or administrated with caution according to the risk level in the three positive groups, while they can be prescribed in the negative group. The effectiveness of HLA screening prior to the beginning of aromatic AEDs administration will be observed by the reduction of overall incidence of AEDs-induced cADRs.

Study Type

Interventional

Enrollment (Anticipated)

4000

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Wei-Ping Liao, M.D.,Ph.D.
  • Phone Number: +86-20-34152625
  • Email: wpliao@163.net

Study Contact Backup

Study Locations

    • Guangdong
      • Guangzhou, Guangdong, China, 510260
        • Recruiting
        • The Second Affiliated Hospital of Guangzhou Medical Universty
        • Contact:
          • Wei-Ping Liao, M.D., Ph.D.
          • Phone Number: +86-20-34152625
          • Email: wpliao@163.net
        • Contact:
        • Principal Investigator:
          • Wei-Ping Liao, M.D., Ph.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients who are going to receive a kind of aromatic AEDs including CBZ, OXC, LTG, PHT, and PB as a new therapy. An AED was deemed newly commenced if there was no record of its prescription in at least the previous 12 months.
  2. Ethnic Han Chinese. None of the biological grandparents of the participants were from other races.

Exclusion Criteria:

  1. individuals who are not of Han Chinese descent.
  2. individuals who had undergone bone marrow transplantation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group with two strong risk factors
When HLA screening before commencing aromatic AEDs shows positive for both HLA-A*24:02 and HLA-B*15:02 in a patient, aromatic AEDs were not administrated for this patient.
When the risk HLA alleles are tested positive for the patients, aromatic AEDs were avoided or administrated with caution according to the risk level.
Experimental: Group with one strong risk factors

When HLA screening before commencing aromatic AEDs shows positive for HLA-B*15:02, carbamazepine (CBZ) was not administrated, and other aromatic AEDs were prescribed with caution or avoided if alternative non-aromatic AEDs can be prescribed instead.

When HLA screening before commencing aromatic AEDs shows positive for HLA-B*15:01 or HLA-A*24:02, aromatic AEDs were prescribed with caution or avoided if alternative non-aromatic AEDs can be prescribed instead.

When the risk HLA alleles are tested positive for the patients, aromatic AEDs were avoided or administrated with caution according to the risk level.
Experimental: Group with one potential risk factors
When HLA screening before commencing aromatic AEDs shows positive for any potential risk allele such as HLA-B*15:11, HLA-A*02:01and HLA-DRB1*01:01, aromatic AEDs were prescribed with caution or avoided if alternative non-aromatic AEDs can be prescribed instead.
When the risk HLA alleles are tested positive for the patients, aromatic AEDs were avoided or administrated with caution according to the risk level.
Experimental: Group without known risk factors
When HLA screening before commencing aromatic AEDs shows negative for any known HLA risk allele , aromatic AEDs was administrated to these patients.
When the risk HLA alleles are tested positive for the patients, aromatic AEDs were avoided or administrated with caution according to the risk level.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
AEDs-induced cADRs incidence
Time Frame: 3 months
the incidence of AEDs-induced cADRs within the first 3 months of commencing an aromatic AED
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2017

Primary Completion (Anticipated)

June 1, 2021

Study Completion (Anticipated)

June 1, 2021

Study Registration Dates

First Submitted

June 9, 2017

First Submitted That Met QC Criteria

June 9, 2017

First Posted (Actual)

June 12, 2017

Study Record Updates

Last Update Posted (Actual)

September 5, 2018

Last Update Submitted That Met QC Criteria

September 2, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Other Study ID Numbers

  • 2017-hs-30

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

The clinical data and HLA genotype of the participant will be shared in the collaborators

IPD Sharing Time Frame

2017 July - 2021 July

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Clinical Study Report (CSR)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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