Primary Immune Thrombocytopenia (ITP)
Conditions
Keywords
ITP, recombinant human thrombopoietin, eltrombopag
Brief summary
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.
Interventions
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.
DRUGEltrombopag PfOS
EPAG-PFOS (Shenyang Sunshine Pharmaceutical Co., Ltd.; 25 mg, calculated as C₂₅H₂₂N₄O₄) * Drug-Food Interactions: Administer at least 2 hours before or 4 hours after antacids, dairy products, or cationic mineral supplements. * Dosing: Initiate at 50 mg once daily; adjust the dose in 25 mg increments (not to exceed 75 mg/day) or modify dosing frequency every 2 weeks based on platelet count.
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 12-75 years, either sex; 2. ECOG performance status 0-1; 3. Diagnosis of ITP confirmed by bone marrow biopsy (valid within 3 months) or other relevant examinations; 4. Patients who failed short-term rhTPO second-line treatment (≤14 days of medication) (PLT \< 30×10⁹/L); 5. Major organ function must meet the following requirements (based on normal values at the clinical trial center): 1. 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; 2. 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; 3. 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; 6. 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; 7. 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; 8. 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; 9. No contraindications to rhTPO and eltrombopag use; 10. Voluntary participation in this study, signed informed consent, good compliance, and willingness to cooperate with follow-up.
Exclusion criteria
1. Refractory ITP patients (failure of first-line and second-line thrombopoietic drugs and CD20 monoclonal antibody treatment, or splenectomy failure/postoperative relapse); 2. Pregnant or lactating patients; 3. 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.; 4. 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; 5. 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); 6. 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; 7. 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; 8. Coexisting malignancy severely affecting survival; 9. 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; 10. Use of any herbal medicine or nutritional supplements within 1 week before study start, except vitamin and mineral supplements; 11. Currently having severe or uncontrolled infection (CTC AE Grade 2 infection); 12. 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); 13. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | This indicator assesses the proportion of patients who reach the clinically significant platelet count threshold early after switching to the study intervention protocol. The specific definition is: the percentage of patients with a measured platelet count of ≥ 50 × 10⁹/L in the visit at the 6th week (day 42, with the visiting window being days 41 to 43) after treatment conversion, among the total number of patients in the protocol analysis set. This threshold (50×10⁹/L) is generally regarded as significantly reducing the risk of spontaneous bleeding and is one of the important criteria for evaluating treatment response. Calculation formula: (Number of patients with platelet count ≥ 50×10⁹/L at the 6th week visit/total number of patients conforming to the protocol analysis set) × 100%. |
| 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. | The time from the initiation of treatment switching to the first PLT count ≥30×10⁹/L (in days) was recorded. For patients who did not achieve CR or R by the end of the study, the last efficacy assessment date was used as the censored date. |
| 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 ). | Proportion of patients who, after achieving initial response and without other ITP therapeutic interventions or rescue treatments, maintain PLT \> 30×10⁹/L at week 6 or 12 without bleeding symptoms. |
| 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). | This indicator aims to dynamically evaluate hematological responses of different grades during the treatment period and the follow-up period. The specific definition is as follows: 1) Total response rate: It is defined as the proportion of patients with a platelet count of ≥30×10⁹/L, at least doubling from the baseline, and no bleeding manifestations. 2) Proportion of patients with platelet count ≥50×10⁹/L: Defined as the percentage of such patients. 3) Complete remission rate: Defined as the proportion of patients with a platelet count of ≥100×10⁹/L and no bleeding manifestations. The above three proportions will be calculated separately at each scheduled visit point. The denominators of each proportion are the total number of patients in the protocol analysis set who have valid platelet count and bleeding assessment data at the corresponding visit points. |
| 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. | Duration of response defined as time from first achievement of CR or Response (R) until disease relapse, study discontinuation, or loss to follow-up. For patients discontinuing or lost to follow-up, the last efficacy evaluation date is used as the outcome event; for patients not observed to relapse by study end and dropping out for various reasons, the last efficacy evaluation date is used as censored data. |
Outcome results
None listed