Open-label, Randomized Controlled Trial to Assess Efficacy and Safety of Rituximab in Patients With Acute Rheumatic Fever in Africa
试验速览
- 阶段
- 2 期
- 状态
- 暂停
- 发起方
- 入组人数
- 234
- 试验地点
- 1
- 主要终点
- Rheumatic valvular lesions rate
研究概览
简要总结
Acute Rheumatic Fever is an autoimmune inflammatory post-infectious syndrome, mainly caused by type A streptococcus. It is characterized as an inadequate immune response. It may provoke carditis, combined with articular, skin and neurologic signs. Only carditis, prevalent in 60% of acute rheumatic diseases, may provoke valvular sequels, which define rheumatic cardiopathy. Antibiotherapy based on penicillin is the standard treatment of both acute rheumatic fever and its prevention. Although no anti-inflammatory treatment has proved its efficacy, with or without steroids anti-inflammatory treatments are administered in acute episode of ARF. Up to date, only prevention strategies have shown efficacy.
详细描述
Acute Rheumatic Fever is an autoimmune inflammatory post-infectious syndrome, mainly caused by type A streptococcus. It is characterized as an inadequate immune response. It may provoke carditis (which associates valvular leakages, cardiac conduction system troubles, and pericardial signs), combined with articular, skin and neurologic signs. Only carditis, prevalent in 60% of acute rheumatic diseases, may provoke valvular sequels, which define rheumatic cardiopathy. Prevalence of acute rheumatic disease (ARD) in pproximately 6 cases per 1000 children in Sub-Saharan Africa countries, whereas prevalence in developed countries is less than a case per 100 000 children, with an annual incidence of 470 000 cases and almost 230 000 deaths annually worldwide. Carditis affect between 15 and 20 million people worldwide, mostly children and young adults from low and middle-income countries. This prevalence may be underestimated. In 2007, our team conducted a study in Mozambique and Cambodia that highlighted that, through a screening based on systematic echocardiography in children from several schools, approximately 2/3 of them had asymptomatic and unknown cardiac lesions, which cannot be screened only with a clinical examination. Role of B-type lymphocytes (B cells) in auto-immune diseases physiopathology is nowadays largely accepted and justifies, in certain auto-immune diseases, the use of therapeutics that target and destroy B cells. Rituximab is a CD-20-specific monoclonal chimeric antibody, indicated to treat B lymphomas, where its efficacy and safety have changed the management of these diseases. Recently, it is thought to use Rituximab in auto-immune diseases. Antibiotherapy based on penicillin is the standard treatment of both acute rheumatic fever and its prevention. Although no anti-inflammatory treatment has proved its efficacy, with or without steroids anti-inflammatory treatments are administered in acute episode of ARF. Up to date, only prevention strategies have shown efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 5 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children aged between >= 5 and < 17 years old;
- •Diagnosed acute rheumatic fever with at least one progressive rheumatic valvular lesion confirmed through a cardiac echography.
- •Informed consent, signed and dated by both parents or legal guardians of the patient
排除标准
- •Simultaneous active infection, such as HIV, hepatitis B, C, tuberculosis, Epstein-Barr virus (EBV), or history of frequent, unusual or serious infections ;
- •Pathologies likely to affect immunity (cancer, multiple sclerosis, diabetes, other auto-immune diseases)
- •Recent history of drug administration that may affect the immune system, for the past 4 weeks (immunosuppressive drugs, corticosteroids, anticancer drugs);
- •Hypersensitivity reaction to rituximab or one of its components. Hypersensitivity to penicillin
- •History of monoclonal antibodies administration
- •Recent vaccination (less than a month) or planned within the 12 months after randomization;
- •History of heart failure
- •Renal failure with a creatinine clearance <45 ml/min/1,73m²
- •Pregnancy (a negative urinary test is necessary for women who had their first menstruations or aged 14 years old and more)
- •Patients diagnosed with Guillain-Barré syndrome
- •Patient with at least one of the following biological features : Hemoglobin < 8,5 g/dL, Platelets < 100 G/L, Neutrophils < 1,5 G/L, Leucocytes < 3 G/L, AST or ALT increased > 2,5 the normal superior limit)
- •Any acute or chronic infection clinically significant which would limitate the patient's capacity to follow up the study protocol, which remains under appreciation of the investigator.
- •Any participation in another clinical trial in the 6 months before the pre-randomization visit
研究组 & 干预措施
Rituximab plus standard of care (RTX)
Rituximab i.v of two perfusions (375 mg/m²) administered in a 14 day-interval added to a standard of care treatment
干预措施: Rituximab added to standard of care treatment (Drug)
Standard of care treatment (Control)
Standard of care treatment
干预措施: standard of care treatment alone (Drug)
结局指标
主要结局
Rheumatic valvular lesions rate
时间窗: 6 months post randomization
Rheumatic valvular lesions rate, measured by echocardiography
次要结局
- Incidence of rheumatic valvular lesions(14 days, 3, 6 and 12 months post-randomization)
- Serious adverse events rates(at 14 days, 3, 6, and 12 months after randomization)