Drug Switching Strategy Study After rhTPO Second-Line Treatment Failure in ITP: A Randomized Controlled Trial Comparing High-Dose rhTPO Versus Eltrombopag
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 112
- 主要终点
- Platelet Response Rate (RR) at 6 weeks after switching treatment: proportion of patients with PLT ≥ 30×10⁹/L, at least 2-fold increase from baseline platelet count, and no bleeding manifestations
研究概览
简要总结
This study is a prospective, multicenter, randomized controlled study, planning to enroll 110 ITP patients who failed to respond to conventional-dose rhTPO (300 IU/kg/d) after 14 days of treatment (PLT < 30×10⁹/L). After a 2-week washout period, they will be randomized to the rhTPO double-dose group (Group A) and EPAG-pfos group (Group B), with blood routine monitored weekly and doses adjusted according to platelet levels, comparing the response rates of the two groups at 6 weeks after switching 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
- None
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 12-75 years, either sex;
- •ECOG performance status 0-1;
- •Diagnosis of ITP confirmed by bone marrow biopsy (valid within 3 months) or other relevant examinations;
- •Patients who failed short-term rhTPO second-line treatment (≤14 days of medication) (PLT < 30×10⁹/L);
- •Major organ function must meet the following requirements (based on normal values at the clinical trial center):
- •Blood routine: absolute neutrophil count (ANC) ≥ 1.5×10⁹/L; no abnormalities other than ITP, except: a) PLT < 30×10⁹/L at Day 1 visit or within 48 hours of Day 1 is acceptable for enrollment; b) Hemoglobin: if anemia is clearly due to ITP (excessive bleeding related to thrombocytopenia), subjects with hemoglobin below the lower limit of normal may be enrolled based on investigator judgment;
- •Blood biochemistry: total bilirubin (TBIL) ≤ 1.5×ULN; ALT, AST, or ALP ≤ 3×ULN; serum creatinine (Cr) ≤ 1.5×ULN with creatinine clearance ≥ 50 mL/min;
- •Coagulation function: prothrombin time (PT) within ±3s of normal range; activated partial thromboplastin time (APTT) ≤ 1.5×ULN unless on medications known to alter INR and APTT; no history of coagulation abnormalities other than ITP;
- •Previous ITP combination treatments including platelet transfusion, immunoglobulin, immunomodulators, and cyclophosphamide rescue therapy must have ended ≥2 weeks before enrollment; corticosteroids or TPO-class drug treatments must have ended ≥2 weeks before study start;
- •Patients on immunosuppressants (including corticosteroids, azathioprine, danazol, cyclosporin A, mycophenolate mofetil) or platelet-elevating traditional Chinese medicine maintenance therapy must have stable therapeutic doses for at least the most recent month; patients receiving CD20 monoclonal antibody must have stopped treatment ≥6 months before enrollment; splenectomy patients may enroll ≥6 months after surgery;
- •Women of childbearing potential must have negative serum pregnancy test within 24 hours before first dose; all subjects must agree to use effective contraception during the study and for 6 months after study treatment completion;
- •No contraindications to rhTPO and eltrombopag use;
- •Voluntary participation in this study, signed informed consent, good compliance, and willingness to cooperate with follow-up.
排除标准
- •Refractory ITP patients (failure of first-line and second-line thrombopoietic drugs and CD20 monoclonal antibody treatment, or splenectomy failure/postoperative relapse);
- •Pregnant or lactating patients;
- •Evidence of secondary causes of ITP (e.g., untreated Helicobacter pylori infection, leukemia, lymphoma, autoimmune diseases such as SLE, Hashimoto's thyroiditis) or drug-induced (e.g., anticonvulsants, antibiotics, heparin), or bicytopenia/pancytopenia such as Evans syndrome, immune-related cytopenias, etc.;
- •History or current presence of primary diseases other than ITP causing thrombocytopenia (e.g., primary myelodysplastic syndrome [MDS], congenital bone marrow failure diseases [e.g., Fanconi anemia, dyskeratosis congenita], aplastic anemia [AA]), and judged by investigator as unsuitable for this study;
- •History of intracranial hemorrhage or other important organ severe bleeding (>CTC AE Grade 3), or history of symptomatic gastrointestinal bleeding (e.g., hematemesis, melena) within 6 months before screening (occult blood test positivity without symptoms/signs and hemorrhoids excluded);
- •History of any arterial or venous thrombosis within 6 months before enrollment (including stroke, TIA, MI, DVT, or PE) AND presence of at least 2 of the following risk factors: hormone replacement therapy, oral contraceptives (including estrogen), smoking, diabetes, hypercholesterolemia, drug-controlled hypertension, hereditary coagulation disorders;
- •Severe cardiovascular disease within 6 months before enrollment (NYHA Class III-IV), known arrhythmia increasing thromboembolic risk such as atrial fibrillation, coronary stent implantation, angioplasty, or post-CABG patients;
- •Coexisting malignancy severely affecting survival;
- •Continuous use of medications affecting platelet function (including but not limited to aspirin, clopidogrel, and/or NSAIDs) or anticoagulant therapy >3 days from 2 weeks after study start until study end;
- •Use of any herbal medicine or nutritional supplements within 1 week before study start, except vitamin and mineral supplements;
- •Currently having severe or uncontrolled infection (CTC AE Grade 2 infection);
- •Laboratory or clinical evidence of HIV infection, previous hepatitis C clinical history, previous hepatitis B infection, or active hepatitis/active tuberculosis at screening. Screening laboratory tests indicating hepatitis C or hepatitis B infection (defined as positive HBsAg; additionally, if HBsAg negative but HBcAb positive, regardless of HBsAb status, HBV DNA testing is required, and if positive, subject should be excluded);
- •Patients considered by investigator as unsuitable for this trial due to any other medical, social, or psychological factors that may affect safety or compliance with study procedures.
研究组 & 干预措施
EPAG-pfos Group (Group B)
EPAG-pfos (Shenyang Sunshine Pharmaceutical Co., Ltd.; specification: 25 mg [calculated as C25H22N4O4])
- Administration Separation: Antacids, dairy products, and cationic mineral supplements should be taken at least 2 hours before or at least 4 hours after administration of this product.
- Starting Dose: 50 mg daily.
- Dose Adjustment: Dose adjusted every 2 weeks based on PLT levels in 25 mg increments (not exceeding 75 mg/d) or dosing frequency: ① If no response at 2 weeks, increase from 50 mg/d to maximum dose 75 mg/d; if ineffective after 2-4 weeks at maximum dose, discontinue; ② When 150×10⁹/L ≥ PLT ≥ 50×10⁹/L, maintain current dose, continuous or alternate-day maintenance therapy; ③ When 250×10⁹/L ≥ PLT > 150×10⁹/L, reduce dose by 25 mg from current dose, continuous or alternate-day therapy; ④ When PLT > 250×10⁹/L, suspend EPAG-pfos. If PLT drops to <100×10⁹/L, patient may restart EPAG-pfos treatment.
干预措施: Eltrombopag PfOS (Drug)
rhTPO Double-Dose Group (Group A)
rhTPO (Shenyang Sunshine Pharmaceutical Co., Ltd., National Medical Product Approval No. S20050048, specification 15000U/ml), starting dose 600 IU/kg/d, continuous subcutaneous injection, blood routine monitored weekly, dose adjusted according to platelet levels. ① Patients with PLT ≥ 50×10⁹/L for two consecutive tests enter maintenance therapy, reducing frequency to alternate-day dosing to maintain PLT at 50-150×10⁹/L; ② When 250×10⁹/L ≥ PLT > 150×10⁹/L, reduce rhTPO dose to 300 IU/kg/d, alternate-day dosing; ③ When PLT > 250×10⁹/L, suspend rhTPO. If PLT drops to <100×10⁹/L, patient may restart rhTPO
干预措施: Recombinant Human Thrombopoietin（rhTPO） (Drug)
结局指标
主要结局
Platelet Response Rate (RR) at 6 weeks after switching treatment: proportion of patients with PLT ≥ 30×10⁹/L, at least 2-fold increase from baseline platelet count, and no bleeding manifestations
时间窗: 6th week after treatment conversion (day 42, visitation window allowed: Day 41 to day 43)
This primary endpoint was defined as the proportion of patients who met the "platelet response" criteria at the 6th week (±1 days) after switching from baseline treatment to the intervention plan of this study. "Platelet response" requires the simultaneous satisfaction of the following three conditions: 1) Platelet count ≥ 30 × 10⁹/L; 2) The platelet count has increased by at least twice compared to the baseline value; 3) There were no bleeding events requiring medical intervention or having clinical significance (WHO bleeding grade 0-1). The calculation formula is: (Number of patients achieving response/total number of patients conforming to the protocol analysis set) × 100%.
次要结局
- Proportion of patients with at least one PLT ≥ 50×10⁹/L at week 6(Week 6 after treatment conversion (Day 42, visitation window allowed: Day 41 to day 43))
- Time to Response (TTR)(The time from the initiation of treatment switching to the first PLT count ≥30×10⁹/L (in days) was recorded. Visiting window allowed: Days 1 to 42.)
- Sustained Response Rate (SRR)(At the 6th or 12th week after treatment conversion (day 42 or day 85 , visitation window allowed: days 41 to 43 or days 82 to 88 ).)
- Response Rate (RR), proportion with PLT ≥ 50×10⁹/L, and Complete Response rate (CR, i.e., PLT ≥ 100×10⁹/L without bleeding manifestations) at each visit.(Weeks 1, 2, 3, 4, 5, 6, 8, 10, and 12 after treatment conversion (according to the protocol visit plan).)
- Duration of response(From the date of first achieving remission (CR/R) until the end of the study visit (week 12，Day 85 ±3) or the date of early termination of the study.)