Efficacy and Mechanism of Anti-CD20 Antibodies in Systemic Lupus Erythematosus Associated Pulmonary Arterial Hypertension Based on Multi Omics Studies
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- pulmonary vascular resistance (PVR)
研究概览
简要总结
This is a prospective, single-arm, single-center, explorative clinical trial to evaluate the effect of Rituximab on disease progression in subjects with SLE-PAH receiving concurrent stable-dose standard medical therapy. The study will focus on assessment of clinical response and safety measures longitudinally. In addition, the biomarker of treatment efficacy with Rituximab and pathogenic autoantibody response in this disease will be investigated.
详细描述
This is a prospective, single-arm, single-center, explorative clinical trial to evaluate the effect of Rituximab on disease progression in subjects with SLE-PAH receiving concurrent stable-dose standard medical therapy with a prostanoid, endothelin receptor antagonist, phosphodiesterase 5 (PDE-5) inhibitor, and/or guanylate cyclase stimulators.
Objective. The study will focus on assessment of clinical response and safety measures longitudinally.The primary objective of this study is to explore the safety and efficacy of Rituximab in patients with SLE-PAH. In addition, the biomarker of treatment efficacy with Rituximab and pathogenic autoantibody response in this disease will be investigated.
Study population. Subjects with SLE-PAH with mean pulmonary artery pressure ≥25mmHg, pulmonary artery wedge pressure ≤15mmHg, and pulmonary vascular resistance > 3WU as measured by right heart catheterization will be enrolled. The diagnosis of SLE-PAH should be confirmed by a rheumatologist experienced in the diagnosis and treatment of systemic lupus erythematosus in conjunction with a cardiologist specializing in management of PAH. Both specialists will be part of the study team at each site.
Treatment. Rituximab will be administered as two IV infusions of 1000 mg each, given two weeks apart at Day 0 and Week 2. All subjects will receive 40 mg of prednisone orally the night before and morning of each infusion with diphenhydramine and acetaminophen orally thirty to sixty minutes prior to each infusion of rituximab. Subjects will remain on their baseline standard medical regimen.
Fifty eligible subjects will be accrued. Each potential study subject will provide written informed consent prior to screening procedures. All inclusion and exclusion criteria must be met at time of recruitment prior to receipt of the first dose of rituximab (Day 0, Treatment Initiation).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject has provided written informed consent.
- •Subject must be between the ages of 18 and 65, inclusive at the time of recruitment
- •Clinical diagnosis of systemic lupus erythematosus. Diagnosis of SLE-PAH within the past 5 years, with a mean pulmonary arterial pressure (mPAP) of ≥ 25 mmHg, PAWP ≤15mmHg, mean PVR of > 3 Wood units at entry.
- •WHO Functional Class II, III, or IV.
- •Subjects must have been treated with background medical therapy for PAH (prostanoid, endothelin receptor antagonist, PDE-5 inhibitor, and/or guanylate cyclase stimulators) for a minimum of 8 weeks and have been on stable dose(s) of those medical therapy(ies) for at least 4 weeks prior to randomization with no expectation of change for 24 weeks after randomization.
排除标准
- •Treatment with immunocompromising biologic agents (including, but not limited to TNF inhibitors, anakinra, abatacept, and tocilizumab) within 4 weeks prior to treatment initiation or treatment with infliximab within 8 weeks prior to treatment initiation.
- •SLE combined with important organ damage endangers life:
- •Neuropsychiatric lupus with high risk such as status epilepticus;
- •Refractory thrombocytopenic purpura has a clear bleeding tendency;
- •Pulmonary alveolar hemorrhage leads to respiratory failure;
- •Uncontrolled infection;
- •Severe organ dysfunction:
- •Patients with moderate or severe liver function impairment (Child-Pugh grade B and C);
- •Patients with left ventricular dysfunction (left ventricular ejection fraction<45%);
- •Other diseases are limited to completing a 6-minute walking test: angina pectoris, vascular, musculoskeletal lesions, etc
- •Abnormal laboratory test: platelet<100 × 109/L, or hemoglobin<9 g/dL, or white blood cell count<3 × 109/L, or alanine aminotransferase (ALT)/aspartate aminotransferase (AST) greater than 1.5 times the upper limit of normal value, or total bilirubin and blood lipids greater than 2 times the upper limit of normal value
- •Persistent hypotension, i.e. systolic blood pressure (SBP)<90 mmHg
- •PAH caused by any reason other than SLE: other rheumatic diseases (such as SSc, rheumatoid arthritis, dermatomyositis, etc.); Portal hypertension, hereditary hemorrhagic telangiectasia, etc; Congenital heart disease; Suspicious drugs and poisons;
- •Chronic hypoxic disease related pulmonary hypertension: moderate or severe obstructive pulmonary disease: FEV1<55%; Moderate or severe restrictive pulmonary disease: TLC<60%;
- •Chronic thromboembolic pulmonary hypertension: Pulmonary ventilation/perfusion imaging indicates moderate to high suspicion of pulmonary thromboembolism;
- •Existing infections or uncontrollable infections that require antibiotic or antiviral treatment;
- •Women who are breastfeeding or pregnant or who plan to become pregnant during the study;
- •History of malignant tumors in the past 5 years
- •Mental, addictive, or other illnesses that restrict patients from providing informed consent or complying with research requirements;
- •Any condition or treatment that the investigator believes puts the subject at an unacceptable risk as a test participant.
研究组 & 干预措施
Rituximab group
Rituximab will be administered as two IV infusions of 1000 mg each, given two weeks apart at Day 0 and Week 2. All subjects will receive 40 mg of prednisone orally the night before and morning of each infusion with diphenhydramine and acetaminophen orally thirty to sixty minutes prior to each infusion of rituximab. Subjects will remain on their baseline standard medical regimen.
干预措施: Rituximab (Drug)
结局指标
主要结局
pulmonary vascular resistance (PVR)
时间窗: 0-24 weeks
PVR as assessed by right heart catheterization, the gold standard method to assess cardiopulmonary haemodynamics. Standardized Fick-based pulmonary vascular resistance (PVRf, in Woods Units) are calculated as follows: PVR = TPG / CO, where TPG = Transpulmonary Gradient (mmHg), CO = Cardiac Output (L/min)
次要结局
- Right atrium Pressure (RAP)(0-24 weeks)
- Patients' quality of life(0-24 weeks)
- SLEDAI(0-24 weeks)
- 6MWD(0-24 weeks)
- Clinical worsening(0-24 weeks)
- BNP/NT proBNP(0-24 weeks)
- Cardiac Index (CI)(0-24 weeks)
- low-risk stratification(0-24 weeks)