Study on the Safety of Administering Isoniazid to Systemic Lupus Erythematosus Patients to Prevent Tuberculosis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Drug Induce Hepatitis
研究概览
简要总结
Systemic Lupus Erythematosus (SLE) is a prototypical systemic autoimmune disease characterized by heterogeneity, multisystem involvement, and production of multiple autoantibodies. Clinical features can vary, from mild skin and joint involvement to severe and life-threatening conditions.
Patients with lupus are more susceptible to infections, in addition to being immunocompromised, and due to the administration of corticosteroid and cytotoxic drugs. The presence of these infections is a cause of death in lupus disease in addition to the activity of the disease itself, especially in Asia-Pacific countries. One infection that often occurs in lupus is Tuberculosis (TB).
Efforts have been made to prevent TB infection in vulnerable populations, including isoniazid (INH) prophylaxis. In 2010, World Heatlh Organization issued guidelines for HIV patients to receive INH prophylaxis to prevent TB infection. The implementation of Isoniazid Preventive Therapy (IPT) is quite cheap using INH with mild side effects.18 A meta-analysis study of INH prophylaxis in patients with HIV found that the efficacy of this prophylaxis significantly reduced TB incidence by 35% with an RR of 0.65%. In addition, INH was found to be safe, with no significant increase in drug reactions, according to a meta-analysis of prophylaxis studies in HIV patients.
However, there is no guideline for INH prophylaxis for SLE patients, as there is for HIV patients, due to lack of data on this issue.
Studies on the effectiveness of INH prophylaxis on the prevention of TB infection for SLE patients should be conducted, but before that, studies on the safety of INH therapy in SLE patients should be conducted.
详细描述
Systemic Lupus Erythematosus (SLE) is a prototypical systemic autoimmune disease characterized by heterogeneity, multisystem involvement, and production of multiple autoantibodies. Clinical features can vary, from mild skin and joint involvement to severe and life-threatening conditions. The course of lupus is highly variable in the form of relapses and remissions, with mild and severe forms that can be life-threatening. Treatments for SLE includes steroids and immunosuppressants to control disease activity.
Patients with lupus are more susceptible to infections, in addition to being immunocompromised, and due to the administration of corticosteroid and cytotoxic drugs. The presence of these infections is a cause of death in lupus disease in addition to the activity of the disease itself, especially in Asia-Pacific countries. One infection that often occurs in lupus is Tuberculosis (TB).
Tuberculosis is still a problem especially in the Asian region, and Indonesia ranks 2nd with the most cases after India according to World Health Organization in 2019. TB infection is found in 10-11.4% of SLE patients in Asia. The incidence of TB in SLE is reported to range from 150/100,000 patients per year in Turkey to 2,450/100,000 patients per year in India. The annual risk of TB in SLE patients is higher than the normal population. Registry data at Hasan Sadikin Hospital Bandung showed that 11.4% or 93 out of 813 SLE patients were infected with TB after being diagnosed with SLE.
Risk factors for increased TB infection in SLE patients, in addition to SLE disease activity itself (SLEDAI score >12), renal involvement, lymphopenia, and cumulative dose of steroids used by the patient, are also due to long duration of illness and previous history of TB.
Tuberculosis is also one of the infections that cause death in SLE patients. Mortality from TB in Asian countries ranged from 5-31%. A study in the Philippines found that 14.8% of SLE patients with TB died, those who died had disseminated TB or miliary TB.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Double blinded
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •SLE patients with conditions of :
- •No signs and symptoms of active TB
- •Not under TB treatment
- •No History of TB, malignancy, HIV, liver function test abnormality
- •Not in pregnancy/lactation
- •No other active infections
- •Remission or low to moderate disease activity state
- •Consented to join the study completely
排除标准
- •SLE patients with conditions of :
- •History of allergy to Isoniazid
- •Chronic liver disease, including chronic hepatitis B or C virus
- •Malignancy
- •Pregnancy
研究组 & 干预措施
Treatment Group
SLE patient at the Hasan Sadikin Rheumatology Outpatient Clinic and registered as Lupus Registry with remission or mild SLE disease activity. The diagnosis of SLE is based on ACR 1997 criteria or SLE SLICC 2012 criteria. Screening will include history review, physical examinations, chest X-Ray, laboratory test such as CBC, ALT/AST, HbsAg, total anti-HCV, complement (C3), dsDNA, creatinine serum, urinalysis (proteinuria, ACR, RBC, WBC, casts), IGRA, to assess if any subject has no active TB and no chronic liver disease.
Treatment group receiving Isoniazid 5 mg/kg/day (maximum 300 mg/day) with pyridoxine 10 mg/day.
Monitor ALT/AST and SLE disease activity after two weeks, continued monthly for the first three months (1st, 2nd, 3rd) then every three months for up to a year (6th, 9th, 12th months). Routine SLE medication is continued and routinely recorded at every visit.
干预措施: Isoniazid/Pyridoxine (Drug)
Control Group
SLE patient at the Hasan Sadikin Rheumatology Outpatient Clinic and registered as Lupus Registry with remission or mild SLE disease activity. The diagnosis of SLE is based on ACR 1997 criteria or SLE SLICC 2012 criteria. Screening will include history review, physical examinations, chest X-ray, laboratory test such as CBC, ALT/AST, HbsAg, total anti-HCV, complement (C3), dsDNA, creatinine serum, urinalysis (proteinuria, ACR, RBC, WBC, casts) IGRA, to assess if any subject has no active TB and no chronic liver disease.
Control group receiving placebo.
Monitor ALT/AST and SLE disease activity after two weeks, continued monthly for the first three months (1st, 2nd, 3rd) then every three months for up to a year (6th, 9th, 12th months). Routine SLE medication is continued and routinely recorded at every visit.
干预措施: Saccharum Lactis (Drug)
结局指标
主要结局
Drug Induce Hepatitis
时间窗: week 2, months 1, 2, 3, 6, 9, 12
Change in more than twice the upper limit of normal SGOT/SGPT values and improvement after drug discontinuation
SLE disease activity
时间窗: month 1, 2, 3, 6, 9, 12
Based on Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score. The higher the score, the worse. SLEDAI score increase in more than 3=flare
次要结局
未报告次要终点