A randomized controlled pilot trial to compare the efficacy of Rituximab infusion versus intravenous Dexamethasone Pulse therapy in Pemphigus vulgaris and its correlation with phenotypic and functional determinants of B and T cells
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Median time to achieve complete disease remission in Rituximab infusion versus intravenous Dexamethasone pulse therapy group
研究概览
简要总结
Pemphigus vulgaris is a chronic autoimmune muco-cutaneous blistering disease which presents as a dermatological emergency as it predisposes to widespread secondary infection and sepsis, thermal dysregulation, electrolyte imbalance and even death. Treatment of pemphigus vulgaris remains a challenge because of the chronic, persistent nature and high rate of disease recurrence.
Dexamethasone pulse therapy has been the mainstay of treatment for PV in India with long term remissions, cost-effective and a good safety profile. However, certain limitations such as long duration of supervised treatment (1-2 years) left scope for an alternative treatment with better efficacy in shorter time with fewer side effects. Rituximab is anti CD 20 monoclonal antibody and has been successfully used as intravenous infusion to treat recalcitrant pemphigus vulgaris, with good safety profile and clinical remission rates approaching 75%. We propose to compare clinical efficacy of the standard pulse therapy with rituximab treatment, safety profile of the two regimens and cost-effectiveness between the two regimens in a randomized trial.
In addition, we also propose to compare changes in various biochemical and immunological parameters both in skin and blood during different periods of disease activity to assess efficacy of the two regimens and predict disease relapse. These biomarkers will help us in identification of patients at risk of relapse to avoid unnecessary infusions and significant cost savings.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 70.00 Year(s)（—）
- 性别
- All
入选标准
- •Subject with active PV fulfilling any of the two criteria mentioned below: -Clinical signs typical of pemphigus vulgaris and -Histological features of suprabasal acantholysis on hematoxylin and eosin staining -Positive ELISA test for anti dsg1 and dsg3 antibodies
- •Patients giving consent for obtaining blood and skin biopsy samples for various investigations
- •Patients who can obtain i.v. Rituximab (1g 2 doses).
排除标准
- •1.Pure mucosal pemphigus vulgaris 2.Age <18 or > 70 years 3.Has received prior biological therapy in past 2 months 4.Pregnant or lactating women.
- •5.Patients with severe renal or hepatic disease 6.Evidence of paraneoplastic pemphigus 7.Autoimmune blistering disease other than PV 8.Active, unhealed peptic ulcer within 3 months prior to randomization 9.Inherited or acquired immune deficiency 10.Malignancy, lymphoproliferative diseases or previous total lymphoid irradiation 11.Chronic or frequent drug resistant, bacterial infections or presence of severe active infection 12.Bone marrow insufficiency 13.Frequent and / or serious viral infections.
- •14.Systemic or invasive fungal disease within 2 years prior to randomization.
结局指标
主要结局
Median time to achieve complete disease remission in Rituximab infusion versus intravenous Dexamethasone pulse therapy group
时间窗: 24months
次要结局
- Median time to achieve disease control in the 2 groups
- Number of patients in complete remission at 6 months and one year(24months)
- Percentage change in PDAI score and functional disability score
- Number of patients with relapse in both groups
- Median time to develop relapse in both groups(32months)
- Comparison of levels of circulating and lesional T-regulatory and B-regulatory cells between the 2 groups
- Cumulative dose of prednisolone in both groups
- Cost effectiveness analysis between the two groups
- Clinical adverse events in both groups assessed in terms of causality, severity and seriousness
- Determination of biomarkers that would predict disease relapse in two groups:(a) levels of BAFF and APRIL ligands and BAFF R, TACI and BCMA receptors to predict relapse of disease)