HLA Screening in Reducing the Risk of Antiepileptic Drug-induced Cutaneous Adverse Reactions: a Multicenter Clinical Study
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 4,000
- 试验地点
- 1
- 主要终点
- AEDs-induced cADRs incidence
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
- •Ethnic Han Chinese. None of the biological grandparents of the participants were from other races.
排除标准
- •individuals who are not of Han Chinese descent.
- •individuals who had undergone bone marrow transplantation
研究组 & 干预措施
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.
干预措施: HLA screening before commencing aromatic AEDs (Diagnostic Test)
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.
干预措施: HLA screening before commencing aromatic AEDs (Diagnostic Test)
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.
干预措施: HLA screening before commencing aromatic AEDs (Diagnostic Test)
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.
干预措施: HLA screening before commencing aromatic AEDs (Diagnostic Test)
结局指标
主要结局
AEDs-induced cADRs incidence
时间窗: 3 months
the incidence of AEDs-induced cADRs within the first 3 months of commencing an aromatic AED
次要结局
未报告次要终点