Efficacy and Safety of Glucocorticoids Combined With Recombinant Human Thrombopoietin (rhTPO) Sequential Eltrombopag Olamine for Severe Primary Immune Thrombocytopenia (ITP) in Adults
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Sustained response rate (SRR) at 3 months of treatment.
研究概览
简要总结
To address the clinical need for improving early response rates, maintaining sustained responses, reducing relapse rates, and minimizing adverse events in the treatment of immune thrombocytopenia (ITP), the investigators developed a comprehensive in-hospital and post-discharge management strategy. In this study, hospitalized participants will receive a 14-day regimen of high-dose dexamethasone (HD-DXM) plus recombinant human thrombopoietin (rhTPO), followed by a 10-week course of oral eltrombopag olamine dry suspension after discharge. The investigators aim to evaluate the efficacy and safety of this sequential treatment strategy in adult ITP patients.
详细描述
To address the clinical need for improving early response rates, maintaining sustained responses, reducing relapse rates, and minimizing adverse events in the treatment of immune thrombocytopenia (ITP), the investigators developed a comprehensive in-hospital and post-discharge management strategy. This approach is based on the superior early response achieved with recombinant human thrombopoietin (rhTPO) combined with high-dose dexamethasone (HD-DXM), and the favorable efficacy of eltrombopag in maintaining long-term responses and reducing relapse. In this study, hospitalized participants will receive a 14-day regimen of HD-DXM plus rhTPO, followed by a 10-week course of oral eltrombopag olamine dry suspension after discharge. The investigators aim to evaluate the efficacy and safety of this sequential treatment strategy in adult ITP participants, with the goal of enhancing early response, sustaining remission, reducing relapse, and minimizing adverse effects. This study is expected to provide evidence-based support for optimizing ITP treatment.
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
- Single (Investigator)
入排标准
- 年龄范围
- 12 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 12 and 75 years, regardless of gender;
- •ECOG performance status of 0-1;
- •Diagnosis of primary ITP confirmed by bone marrow biopsy (valid within 3 months) and other relevant assessments; baseline platelet count (PLT) <20×10⁹/L within 48 hours prior to administration of study medication;
- •Adequate function of major organs as defined below (based on the clinical laboratory reference ranges of the study center):
- •Hematology: Absolute neutrophil count (ANC) ≥1.5×10⁹/L; no abnormalities unrelated to ITP, except a) PLT <20×10⁹/L at Day 1 or within 48 hours of Day 1 is allowed; b) Hemoglobin: If anemia is clearly due to ITP-related bleeding, hemoglobin lower than the lower limit of normal (LLN) may be permitted at investigator's discretion.
- •Biochemistry: Total bilirubin (TBIL) ≤1.5×ULN; ALT, AST, ALP ≤3×ULN; serum creatinine ≤1.5×ULN and creatinine clearance ≥50 mL/min.
- •Coagulation: Prothrombin time (PT) within ±3 seconds of normal range; activated partial thromboplastin time (APTT) ≤1.5×ULN unless on medications known to alter INR/APTT; no known history of coagulopathy other than ITP.
- •Prior ITP rescue treatments (e.g., platelet transfusion, IVIG, immunomodulators, cyclophosphamide) must have ended or failed at least 2 weeks prior to enrollment (except corticosteroids); TPO-RAs or corticosteroids must be discontinued ≥14 days before study start.
- •Patients on maintenance immunosuppressive therapy (e.g., corticosteroids, azathioprine, danazol, cyclosporine A, mycophenolate mofetil, or traditional Chinese platelet-raising medicine) must be on stable doses for at least 1 month prior to enrollment. Patients previously treated with anti-CD20 antibodies must have discontinued at least 6 months prior; splenectomy patients may enroll ≥6 months post-surgery.
- •Female subjects of childbearing potential must have a negative serum pregnancy test within 24 hours prior to first dosing; all subjects agree to use effective contraception during the study and for 6 months after its completion.
- •No known contraindications to corticosteroids, rhTPO, or eltrombopag and willing to undergo rhTPO followed by eltrombopag treatment.
- •Willingness to participate and ability to provide written informed consent. For participants aged ≥12 years, both the subject and their legal guardian must sign the informed consent form.
排除标准
- •Refractory ITP (failure to respond to first- and second-line TPO-RAs, anti-CD20 therapy, or splenectomy);
- •Pregnant or lactating women;
- •Evidence of secondary ITP (e.g., untreated Helicobacter pylori, leukemia, lymphoma, autoimmune diseases such as SLE, Hashimoto's thyroiditis), drug-induced thrombocytopenia (e.g., due to anticonvulsants, antibiotics, heparin), or multi-lineage autoimmune cytopenias (e.g., Evans syndrome);
- •History or presence of any primary disease other than ITP that may cause thrombocytopenia (e.g., myelodysplastic syndrome, congenital bone marrow failure syndromes such as Fanconi anemia or dyskeratosis congenita, aplastic anemia), as judged by the investigator;
- •History of intracranial hemorrhage or severe bleeding (>CTCAE Grade 3) of vital organs; symptomatic gastrointestinal bleeding (e.g., hematemesis, melena) within 6 months prior to screening (asymptomatic occult blood and hemorrhoids excluded);
- •History of any arterial or venous thrombosis (e.g., stroke, TIA, MI, DVT, PE) within 6 months prior to enrollment and at least two of the following risk factors: hormone replacement therapy, oral contraceptives (including estrogens), smoking, diabetes, hypercholesterolemia, pharmacologically controlled hypertension, hereditary thrombophilia;
- •Severe cardiovascular disease within 6 months prior to enrollment (e.g., NYHA Class III-IV), arrhythmias increasing thrombotic risk (e.g., atrial fibrillation), or history of coronary stenting, angioplasty, or bypass surgery;
- •Concurrent serious or life-threatening malignancy;
- •Use of drugs that significantly affect platelet function (e.g., aspirin, clopidogrel, NSAIDs) or anticoagulants for >3 days within 2 weeks before and during the study;
- •Use of any herbal medicine or nutritional supplement within 1 week prior to study start, except for vitamins and minerals;
- •Ongoing or uncontrolled serious infections (≥CTCAE Grade 2);
- •Laboratory or clinical evidence of HIV infection, active hepatitis C, active hepatitis B, or previous history of these infections. Patients with positive HBsAg are excluded. Those with HBsAg-negative but HBcAb-positive must undergo HBV DNA testing; if positive, they are excluded;
- •Any condition deemed by the investigator to make the subject unsuitable for participation, including but not limited to medical, social, or psychological factors affecting safety or study compliance.
研究组 & 干预措施
Eltrombopag Group
Participants who achieve a complete response (CR) or response (R) after HD-DXM combined with rhTPO treatment will be randomized in a 2:1 ratio into the eltrombopag group or the placebo group.
Observation group: Participants will receive eltrombopag for oral suspension (EPAG-pfos) for ten weeks.
干预措施: Eltrombopag (Drug)
Placebo group
Participants who achieve a complete response (CR) or response (R) after HD-DXM combined with rhTPO treatment will be randomized in a 2:1 ratio into the eltrombopag group or the placebo group.
Control group: Participants did not receive sequential EPAG-pfos treatment.
干预措施: Placebo (Other)
结局指标
主要结局
Sustained response rate (SRR) at 3 months of treatment.
时间窗: 3 months of the study
Sustained response rate (SRR) at 3 months of treatment.
次要结局
- The proportions of patients achieving response (R);(6 months of the study)
- Platelet count levels at 3 months after treatment(3 months of the study)
- The proportions of patients achieving complete response (CR);(6 months of the study)
- The proportions of patients achieving and platelet counts ≥50×10⁹/L;(6 months of the study)
- Sustained response rate (SRR) at 6 months;(6 months of the study)
- Time to response (TTR);(6 months of the study)
- Time from treatment initiation to first achievement of PLT ≥100×10⁹/L;(6 months of the study)
研究者
MEI HENG
Professor
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology