Intravenous Immunoglobulin Plus Oral Prednisone or High-dose Dexamethasone, for Adults With Immune Thrombocytopenia (ITP) With Moderate and Severe Bleeding: a Randomized, Multicentre Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 272
- 试验地点
- 1
- 主要终点
- Time to achieve an initial response (R) within 5 days.
研究概览
简要总结
ITP patients with low platelet count and active bleeding symptoms are at risk of life-threatening bleeding and therefore require a treatment with a rapid effect, reliable, and sustained. The combination of intravenous immunoglobulin (IVIg) and prednisone (1 mg/kg per day), is more rapidly and more frequently effective than high dose methylprednisolone to increase the platelet count. This combination is therefore usually given in patients with platelets count < 20 x 109/L and moderate to severe bleeding manifestations. Based on common practice in France and on French ITP guidelines, on average 50 % of patients with ITP and profound thrombocytopenia do actually receive IVIg (mostly during the initial phase of the disease) corresponding to approximately 1,500 ITP patients per year in France.
Whereas IVIg is usually well tolerated, renal insufficiency and congestive heart failure may occur, moreover IVIg are costly and non-easily available with supply difficulties in many countries including France.
High dose dexamethasone (DXM) (ie: 40 mg/d for 4 days) has recently emerged as a promising treatment for ITP. One recent meta-analysis as well as a controlled prospective trial suggest that the initial overall response was higher (> 80 %) and the time to response was shorter with dexamethasone (DXM) 40 mg/d given for 4 days compared to standard prednisone.
The investigators hypothesize that DXM could be a reasonable non-inferior alternative to IVIg, more convenient for patients with less adverse events and economically cost-effective for patients with moderate and severe bleeding manifestations.
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
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years ≤ 80 years
- •Diagnosis of ITP whatever the duration of the disease (newly diagnosed or relapsed) according to the standard definition
- •Platelet count ≤ 20 x 109/L
- •Any cutaneous and/or any mucosal bleeding manifestations
- •Affiliated to a social security regime
- •Written consent from patient
排除标准
- •Symptomatic COVID-19 disease
- •Life-threatening bleeding defined as Intracranial hemorrhage and/or active organ bleeding (GI tract, urinary tract or menorrhagia with at least a 2 g/dl decrease of hemoglobin value from baseline).
- •Ongoing anticoagulation treatment (Therapeutic Low molecular weight heparins (LMWHs), direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs))
- •Previous non-response to IVIg or DEX
- •Treatment with prednisone (1 mg/kg per day) for more than 3 days
- •Any, contraindications to the prescribed Ig IV or prednisone patent medicine and to Neofordex®
- •Ongoing severe infection
- •Severe Renal insufficiency (DFG < 45 ml.min.1.73m2)
- •Severe Cardiac insufficiency (FEVG < 30 %)
- •Ongoing viral infection (uncontrolled HIV, Viral hepatitis, herpes, varicella, zona).
- •Uncontrolled diabetes (Acido-cetosis)
- •Psychotic state not yet controlled by treatment
- •Inability or refusal to understand or refusal to sign the informed consent from study participation
- •Persons deprived of their liberty by judicial or administrative decision,
- •Persons under legal protection (guardianship, curatorship)
- •Pregnant or breastfeeding woman or ineffective contraception
- •Participation in another interventional study involving human participants or being in the exclusion period at the end of a previous study involving human participants.
研究组 & 干预措施
Experimental group
Oral dexamethasone (Neofordex®) 40 mg (Day1 to Day 4), ± an additional 4-days cycle of dexamethasone between days 10 and 21
干预措施: Neofordex® (Drug)
Control
IVIg (1g/kg D1-D2) plus prednisone (1 mg/kg/day x 21 days (3 weeks))
干预措施: Intravenous immunoglobulins (Drug)
结局指标
主要结局
Time to achieve an initial response (R) within 5 days.
时间窗: 5 days
次要结局
- Proportion of early treatment switches across arms(before day 5)
- Number of responders in patients with positive and negative anti-platelets antibodies in the two arms.(At 6 months)
- Number of outcome in patients with positive and negative anti-platelets antibodies in the two arms.(At 6 months)
- Time to achieve an initial complete response (CR) in the two arms(between Day 1 and Day 5)
- Duration of overall response from Day 1 to the end of the study in the two arms.(Day 1 to 6 months)
- Number of new bleeding manifestations between Day 1 and Day 5 in the two arms.(between Day 1 and Day 5)
- Rates of response (R) and complete response (CR) in the two arms.(at Day 28 and at 6 months)
- Number of new bleeding manifestations in the two arms.(Between Day 5 and Day 28)
- Number of adverse events in the two arms.(up to 6 months)