V-IMMUNE® for Immune Thrombocytopenia: A Prospective Multicenter Study to Evaluate the Efficacy and Safety of Human Immunoglobulin in Adult and Pediatric Participants With Immune Thrombocytopenia. TIP Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 31
- 试验地点
- 2
- 主要终点
- Proportion of patients achieving a platelet count ≥50,000/mm³ on or before Day 9 following the first infusion
研究概览
简要总结
This is a multicenter, prospective clinical trial evaluating the efficacy and safety of V-IMMUNE®, a 5% human normal immunoglobulin formulation administered intravenously, for the treatment of immune thrombocytopenia (ITP) in patients aged ≥1 year. The primary objective is to assess the proportion of patients achieving a platelet count ≥50,000/mm³ on or before Day 9 following the first infusion. The trial employs a single-group design, comparing outcomes to historical controls derived from the literature. Eligible patients must have a confirmed diagnosis of ITP with a platelet count ≤20,000/mm³ and no concurrent conditions likely to cause thrombocytopenia. Key exclusions include non-immune thrombocytopenia, active sepsis, pregnancy or lactation, hypersensitivity to blood products or IgG preparations, and various significant comorbidities (e.g., uncontrolled hypertension, severe hepatic or renal impairment, recent rituximab use). The intervention consists of V-IMMUNE® at a dose of 1 g/kg, administered once daily for two consecutive days, with infusion rates titrated from 0.01 mL/kg/min to 0.06 mL/kg/min. Standard pre-medication protocols (IV normal saline and diphenhydramine) are administered to mitigate infusion-related reactions and reduce the risk of thromboembolic events. Patients will be monitored at multiple time points from baseline through Day 90, with primary efficacy evaluation at Day 9. Secondary endpoints include duration of platelet response, overall treatment response rate, bleeding events, and incidence of infusion-related adverse events.
详细描述
TIP Study V-IMMUNE® for Immune Thrombocytopenia: A prospective multicenter study to evaluate the efficacy and safety of Human Immunoglobulin in adult and pediatric participants with immune thrombocytopenia.
Introduction Immune thrombocytopenia is an autoimmune disease characterized by thrombocytopenia (<100,000/mm³) and an increased risk of bleeding.
Antibody- and/or T-cell-mediated platelet destruction plays a key role in the pathophysiology of immune thrombocytopenia. Newly diagnosed immune thrombocytopenia is characterized by a platelet count <100,000/mm³ within three months of diagnosis. When remission is not achieved or the treatment response is not sustained within three to twelve months, it is considered persistent immune thrombocytopenia. When thrombocytopenia lasts for more than 12 months, it is considered chronic immune thrombocytopenia.
Bleeding in adults with immune thrombocytopenia can range from mild events, such as cutaneous petechiae, to potentially life-threatening events, such as organ bleeding and intracranial hemorrhage. The goal of treatment is to raise the platelet count to levels that can maintain hemostasis, preventing bleeding events or controlling any active bleeding. Hemorrhagic events are associated with worse outcomes and increased mortality in patients with chronic immune thrombocytopenia. Patients who required hospitalization due to bleeding had a 4.9-fold higher risk of mortality at 1 year and a 3.4-fold higher risk at 5 years compared to those who did not experience bleeding. Although most patients with immune thrombocytopenia present only with mild bleeding, the fear of more severe bleeding can negatively impact patients' quality of life. Therefore, experiencing a severe bleeding event is associated with a poor prognosis, increased risk of mortality, and may have substantial negative impacts on a patient's quality of life.
Treatment guidelines for immune thrombocytopenia in adults suggest maintaining platelet counts >20,000-30,000/mm³ in symptomatic patients, as the risk of severe bleeding increases below this threshold. In Brazil, the treatment guideline for immune thrombocytopenia in adults from the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH)/Guideline Project of the Brazilian Medical Association (AMB) recommends corticosteroids and intravenous immunoglobulin (IVIG) as first-line therapy for patients with platelet counts <30,000/mm³ and active bleeding. The combination of these therapies may be indicated in emergency situations.
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
盲法说明
No mask is possible with this intervention
入排标准
- 年龄范围
- 1 Year 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥1 year;
- •Confirmed diagnosis of immune thrombocytopenia ( newly diagnosed, persistent or chronic);
- •Platelet count ≤20,000/mm³ at the time of enrollment;
- •No other conditions that, in the investigator's opinion, could cause thrombocytopenia;
- •Agreement to use effective contraceptive practices/methods throughout the entire study participation by female patients of childbearing potential and able to become pregnant, unless there is a documented medical contraindication.
排除标准
- •Non-immune thrombocytopenia
- •Active sepsis
- •Pregnancy (pregnant or breastfeeding)
- •History of hypersensitivity reaction to blood or blood products, IVIG, or any other IgG preparation
- •Intolerance to any component of V-IMMUNE®
- •Previous diagnosis of IgA deficiency, history of reactions to products containing IgA, or history of anti-IgA antibodies
- •Participation in any other study involving an investigational product
- •Known HIV, HCV, or HBV infection
- •AST (TGO) and/or ALT (TGP) >2.5× the upper limit of normal or 2.5 times baseline values
- •Serum creatinine >2× the upper limit of normal or 2 times baseline values
- •BUN >2.5× the upper limit of normal or 2.5 times baseline values
- •History of NYHA class III or IV heart failure
- •Uncontrolled hypertension with systolic BP >180 mmHg or diastolic BP >100 mmHg
- •A history of hyperviscosity states, transient ischemic attack (TIA), stroke, other thromboembolic events, or acute coronary syndrome (ACS)
- •Neoplasia under active treatment
- •Child-Pugh class B or C liver failure
- •Alcohol, opioid, or psychotropic substance abuse within the past 12 months
- •Receipt of rituximab within 6 months prior to Day 1
- •Acute or chronic conditions (e.g., but not limited to, renal disease or diseases predisposing to renal impairment, coronary artery disease, or protein-losing enteropathy) that, in the investigator's opinion, may interfere with the conduct of the study
- •An acquired health condition such as chronic lymphocytic leukemia, multiple myeloma, or chronic or recurrent neutropenia (absolute neutrophil count <1,000/mm³)
- •History of hemolytic anemia
- •Receipt of any IV immunoglobin preparation within 1 month prior to Day 1
- •Use of corticosteroids, cyclophosphamide, azathioprine, or attenuated androgens with a planned dose increase before Day 10 following IV immunoglobin infusion
研究组 & 干预措施
Intervention arm
Intervention arm will receive a human normal immunoglobulin to be administered intravenously, once daily for 2 consecutive days (Day 1 and Day 2).
If the platelet count is not maintained for the desired duration after the first immunoglobin infusion, and at the discretion of the investigator and the patient/legal representative, participants may receive up to one additional cycle between Day 15 and Day 30
干预措施: 5% (5g/100 ml) intravenous immunoglobin (Biological)
结局指标
主要结局
Proportion of patients achieving a platelet count ≥50,000/mm³ on or before Day 9 following the first infusion
时间窗: 9 days
Evaluate the efficacy of V-IMMUNE® in raising the platelet count of individuals with immune thrombocytopenia to a threshold of 50,000/mm³ or greater by or before Day 9 following the first dose. The proportion will be the ratio between the number of patients who achieved platelet count ≥ 50,000/mm3 / total of patients who received at least one dose of V-Immune® and had laboratory assessments performed at least once during the scheduled visits within 9 days.
次要结局
- Therapeutic response defined as the increase in platelets count(9 days)
- Bleeding occurrence classified according to CTCAE version 5.0(30 days)
- Number of days with platelets count ≥ 50,000/mm3(90 days)
- Proportion of infusions during which one or more adverse events (AEs) occurred(72 hours)
- Total number of adverse events infusion related during the whole study(30 days)
- Mean number of temporally associated adverse events (AEs) per infusion(30 days)
- Proportion of patients who experienced one or more adverse events (AEs)(90 days)