Clinical trial NCT03184597: HLA Screening in Reducing the Risk of Antiepileptic Drug-induced Cutaneous Adverse Reactions
Official title: HLA Screening in Reducing the Risk of Antiepileptic Drug-induced Cutaneous Adverse Reactions: a Multicenter Clinical Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Epilepsy
Neuropathy
Psychiatric Illness
Blepharospasm
Keywords: HLA screening
SJS/TEN
MPE
AEDs
Lead sponsor: Second Affiliated Hospital of Guangzhou Medical University
Sponsor class: OTHER
Collaborators: name: Guangzhou First People's Hospital
name: West China Hospital
name: Guangdong Provincial People's Hospital
name: First Affiliated Hospital of Jinan University
name: Guangdong 999 Brain Hospital
name: First Affiliated Hospital, Sun Yat-Sen University
name: Wuhan Women and Children's Medical Center
name: First People's Hospital, Shunde China
First posted: 2017-06-12
Enrollment: 4000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: AEDs-induced cADRs incidence
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The Second Affiliated Hospital of Guangzhou Medical Universty
state: Guangdong
Study officials:
affiliation: Second Affiliated Hospital of Guangzhou Medical University
name: Wei-Ping Liao, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
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