rhTPO Dose Escalation vs Eltrombopag Switch in ITP

Drug Switching Strategy Study After rhTPO Second-Line Treatment Failure in ITP: A Randomized Controlled Trial Comparing High-Dose rhTPO Versus Eltrombopag

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Primary Immune Thrombocytopenia (ITP)
• Intervention / Treatment: Drug: Recombinant Human Thrombopoietin（rhTPO）; Drug: Eltrombopag PfOS

• Study Type: Interventional
• Enrollment (Estimated): 112
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Recombinant Human Thrombopoietin（rhTPO）; 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.
Active Comparator: 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.	Drug: Eltrombopag 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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%.	6th week after treatment conversion (day 42, visitation window allowed: Day 41 to day 43)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with at least one PLT ≥ 50×10⁹/L at week 6	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%.	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. 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.	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)	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.	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.	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.	Weeks 1, 2, 3, 4, 5, 6, 8, 10, and 12 after treatment conversion (according to the protocol visit plan).
Duration of response	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.	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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of serious adverse events (SAE) during treatment	Any adverse events during treatment (including but not limited to thrombosis, hepatic function abnormalities, rash, etc.). The proportion of patients who experienced any serious adverse events from the start of the first administration to 30 days after the last administration. The definition of serious adverse events follows the ICH-GCP guidelines. The calculation formula is: (the number of patients with SAE/the total number of patients in the safety analysis set) × 100%.	From the first administration to 14 days (approximately 2 weeks) after the last administration.
Bleeding events	This indicator assesses the occurrence and severity of bleeding events during the treatment period and follow-up period. It includes the following two parts: 1) Incidence of bleeding: Defined as the proportion of patients who experienced any grade (including mild and severe) of bleeding events from the start of the first administration to the end of the last follow-up. The calculation formula is: (the number of patients with ≥1 bleeding event/the total number of patients in the safety analysis set) × 100%. 2) Bleeding score: Each bleeding event is graded using the World Health Organization's bleeding grading standard and ITP-BAT bleeding score. The highest bleeding grade for each patient during the treatment period and the cumulative incidence of bleeding events of each grade will be reported.	From the first study medication to the end of the last follow-up (maximum observation period: 12 weeks).
Platelet transfusion rate	Proportion of patients requiring at least one platelet transfusion during the study period. Transfusion records will be based on medical records and will document the cause and dosage of each transfusion.	From the first study medication to the end of the last follow-up (maximum observation period: 12 weeks).
Mean number of platelet transfusions per patient	Average number of platelet transfusions per patient during the study period, calculated as total number of transfusions divided by total number of study population. Transfusion records will be based on medical records and will document the cause and dosage of each transfusion.	From the first study medication to the end of the last follow-up (maximum observation period: 12 weeks).
Mean volume of platelet transfusions per patient	Average volume of platelet transfusions per patient during the study period, calculated as total transfusion units divided by total number of study population. Transfusion records will be based on medical records and will document the cause and dosage of each transfusion.	From the first study medication to the end of the last follow-up (maximum observation period: 12 weeks).
Quality of life scores after treatment	Health-related quality of life was assessed using the EQ-5D-5L (EuroQol 5-Dimension 5-Level) questionnaire. The utility scores range from -0.391 to 1.000, with higher scores indicating better health status. The changes during treatment were evaluated once a week, and the score differences at baseline, at the end of treatment (week 6), and at the end of follow-up (week 12) were compared.	Baseline (before treatment conversion), during treatment conversion (weeks 1 to 6, evaluated once a week), and week 12 after treatment conversion.

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: February 26, 2026
• First Submitted That Met QC Criteria: March 12, 2026
• First Posted (Actual): March 17, 2026

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: eltrombopag; ITP; recombinant human thrombopoietin
• Additional Relevant MeSH Terms: Cytopenia; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Skin Manifestations; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Thrombocytopenia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hemic and Lymphatic Diseases; Purpura, Thrombocytopenic, Idiopathic
• Other Study ID Numbers: IIT2026001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No