Proof of Concept; A Pilot, Randomized, Double-Blind Study of Oseltamivir Versus Placebo for Immune Thrombocytopenia
试验速览
- 阶段
- 3 期
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Mean platelet glycoprotein sialyation
研究概览
简要总结
Immune Thrombocytopenia (ITP) is a disorder resulting in impaired platelet production and enhanced destruction on the basis of autoantibody-mediated mechanisms. Patients with ITP are at increased risk of bleeding and infection. First line therapy includes glucocorticoids, with or without the addition of intravenous immune globulin (IVIg) when a prompt platelet response is desired. The likelihood of stable and safe disease after first-line treatment ranges from 30-60% and risk of relapse requiring additional therapy occurs in 50-80% of patients. Moreover, the toxicity associated with first and subsequent therapy for ITP is substantial.
Oseltamivir is an attractive drug for ITP since it specifically targets a pathophysiologic mechanism that appears to be important for the development of ITP and has a benign side effect profile compared to standard ITP therapy.
Oseltamivir has never been rigorously tested in humans to determine its efficacy in the management of ITP. The investigators therefore propose the first randomized, double blind study to assess the impact of oseltamivir on biological markers in adult patients with ITP. This study will also provide information about the feasibility of recruitment into a definitive trial, which would be coordinated by St. Michael's Hospital.
The research question is: Do adults (≥ 18 years) with ITP treated with oseltamivir at 75mg twice daily for 5 consecutive days have an increase in their mean platelet glycoprotein sialylation compared to those receiving placebo?
This pilot, proof-of-concept, randomized controlled clinical trial will enroll 30 individuals with ITP. Randomization and allocation will occur at a ratio of 1:1. Analysis of the primary outcome measure will occur via analysis of covariance (ANCOVA).
This study has the potential to dramatically change the treatment of ITP. If the results from this study demonstrate a biological effect, and results from the subsequent definitive study are positive, The investigators envision a move away from non-specific immune-blunting therapy such as prednisone, towards tailored therapy with oseltamivir. It could diminish the lifelong summative immunosuppressive therapy burden, associated drug toxicity and improve long- and short-term health outcomes for these patients.
详细描述
Explanation (of rationale for current study):
Despite the encouraging case report described above, oseltamivir has not been rigorously tested in humans to determine its efficacy in the management of ITP. Oseltamivir is an attractive drug for ITP since it specifically targets a pathophysiologic mechanism that appears to be important for the development of ITP and has a benign side effect profile compared to standard ITP therapy. However, more robust evidence that oseltamivir affects desialylation in humans is needed before a definitive, multicenter randomized trial can be justified to funders.
The investigators therefore propose the first randomized, double blind, study to assess the impact of oseltamivir on biological markers in adult patients with ITP. This study will also provide information about the feasibility of recruitment into a definitive trial, which would be coordinated at St. Michael's Hospital (SMH).
Impact:
The most appropriate treatment of patients with persistent ITP represents an area of major clinical interest burdened by unacceptable uncertainty. This study has the potential to dramatically change the treatment of ITP. If the results from the definitive study are positive, the investigators envision a move away from non-specific immune-blunting therapy such as prednisone, towards tailored therapy like oseltamivir. Targeted therapy for ITP is a timely and relevant concept. It could diminish the lifelong summative immunosuppressive therapy burden, associated drug toxicity and improve long- and short-term health outcomes for this patient population.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients ≥ 18 years of age;
- •Patients with primary or secondary (i.e. ITP due to a secondary cause) ITP (autoimmune disorder characterized by isolated thrombocytopenia with no other causes or disorders that can be associated with thrombocytopenia; diagnosis of exclusion);
- •Individuals with lack of sustained complete remission - platelet count <100 x E9/L despite first line therapy (prednisone, dexamethasone, IVIG);
- •Patient's median platelet count over the last 12 months is <100 x E9/L, and must be <100 x E9/L on screening day.
排除标准
- •Concurrent medical or surgical treatment for ITP (e.g. prednisone, dexamethasone, IVIG, anti-RhD immune globulin, azathioprine, cyclosporine, cyclophosphamide, danazol, dapsone, mycophenylate mofetil, rituximab, thrombopoietin mimetics, any investigational agents for ITP, splenectomy);
- •Patient with a platelet count of <20 x E9/L with active significant bleeding based on a bleeding assessment score of Grade 2 at any site by the ITP Bleeding Scale (IBLS);
- •Any immunosuppressive or immunomodulating therapy (not aforementioned) over the last 3 months;
- •Oseltamivir therapy over the last 3 months;
- •Pregnant females (oseltamivir is a class C drug in pregnancy);
- •Lactating females (oseltamivir is detected in low quantities in breast milk).
研究组 & 干预措施
Oseltamivir
Oseltamivir capsule administered orally at 75 mg twice daily for five consecutive days.
干预措施: Oseltamivir (Drug)
Placebo
Placebo capsule administered orally twice daily for five consecutive days.
干预措施: Placebo (Drug)
结局指标
主要结局
Mean platelet glycoprotein sialyation
时间窗: Day 0 and Day 5
Mean platelet glycoprotein sialyation
次要结局
- Proportion of patients who received additional ITP based therapy during the study follow-up period(Day 0, Day 5 and Follow up)
- Percentage of patients who had complete follow-up 12 months after randomization(Day 0, Day 5 and Follow up)
- Percentage of eligible patients successfully recruited(Screening and Day 0)
- Mean platelet count(Day 0, Day 5 and Follow up)
- Anti-platelet glycoprotein antibody specificity/titer(Day 0 and Day 14)
- Number of patients recruited per month(Screening and Day 0)
- Percentage of patients who received the study drug within 12 hours of randomization(Day 0)
- Percentage of patients who received every scheduled dose of the study drug in a blinded fashion(Day 0 and Day 5)
- Frequencies of CD4+ and CD8+ T regulatory cells(Day 0 and Day 14)
- Cytokine profiles(Day 0 and Day 14)
- Effects of antibodies on macrophage- and hepatocyte-mediated Fc-dependent and independent phagocytosis in vitro(Day 0 and Day 14)