Herombopag + rhTPO in Severe Immune Thrombocytopenia

Study Overview
=================
Brief Summary
-----------------
Severe immune thrombocytopenia (ITP) is a life-threatening acquired hemorrhagic disease with dramatically decreased platelet number and clinical bleeding symptoms. Some patients with severe ITP did not respond to first-line treatment including steroids and IVIG. It was critical for them to use effective treatments to promote platelet and reduce the risk of fatal bleeding. In this study, the patients with severe ITP will be treated with hetrombopag, rhTPO, and the combination of hetrombopag and rhTPO, respectively. The effect evaluation includes the increase of platelet number and decrease of bleeding scores. Changes of coagulation, platelet activation, fribrinolysis influence, and thrombotic events will also be accessed for the safety of treatments. The aim of this study is to demonstrate that the combination of hetrombopag and rhTPO for severe ITP is more effective than the other two monotherapy and does not increase thrombotic events or thrombosis risk.

Detailed Description
-----------------
Patients with severe ITP will be randomly assigned to three groups: rhTPO group, Herombopag Group, Herombopag combined with rhTPO group. The effective rate of treatment, the rate and amplitude of platelet increase, the response time of platelet maintenance, and the effect of combination therapy on hemostasis will be compared. At the same time, the investigators will analyze the markers of thrombosis and thrombotic events to assess the safety of combination therapy.

Official Title
-----------------
Evaluating the Efficacy and Safety of the Combination of Herombopag and Human Thrombopoietin (rhTPO) in the Treatment of Patients With Severe Immune Thrombocytopenia (ITP)

Conditions
-----------------
Immune Thrombocytopenia

Intervention / Treatment
-----------------
* Drug: rhTPO
* Drug: Herombopag


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female,70 ≥age≥18； Diagnosed as primary immune thrombocytopenia； Platelet count was less than 10 × 10E9 / L with active bleeding, or bleeding score ≥ 5 points； No use of IVIG, Avatrombopag, Eltrombopag or Romiplostim 2 weeks before treatment； Rituximab was used for at least 2 months, and other immunosuppressants were stable for at least 4 weeks. There was no history of platelet transfusion one week before treatment. Exclusion Criteria: Secondary thrombocytopenia caused by other autoimmune diseases and virus infection was excluded； Patients with active malignant tumors, pregnancy, severe cardiovascular， cerebrovascular diseases and a history of arteriovenous thrombotic diseases were excluded； Patients deemed unsuitable for enrollment by the investigator； Patients with thrombotic disease or serious uncontrolled cardiovascular and cerebrovascular disease; Patients reject to participate in the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients with severe ITP will be randomly assigned to three groups: rhTPO group, Herombopag Group, Herombopag combined with rhTPO group.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rhTPO<br>rhTPO will be injected subcutaneously at 300 u/kg daily for 14 days. | Drug: rhTPO<br>* subcutaneous injection<br>|
| Experimental: Herombopag<br>Herombopag will be taken orally at 5 mg daily for 28 days. | Drug: Herombopag<br>* Orally by mouth<br>|
| Experimental: Herombopag in combination of rhTPO<br>Herombopag will be taken orally at 5 mg daily for 28 days，while rhTPO will be injected subcutaneously at 300 u/kg daily for 14 days | Drug: rhTPO<br>* subcutaneous injection<br>Drug: Herombopag<br>* Orally by mouth<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | platelets ≥30*10E9/L, and at least 2 times higher than the baseline platelet count, and there is no hemorrhagic manifestations | From randomization to 28 days after rhTPO/Herombopag/Herombopag+rhTPO treatment | 
| The rate and magnitude of the increase in platelet count | The rate and magnitude of the increase in platelet count after treatment | From randomization to 28 days after rhTPO/Herombopag/Herombopag+rhTPO treatment | 
| Platelet maintenance response time | Platelets stay above 30*10E9/L | From randomization to 28 days after rhTPO/Herombopag/Herombopag+rhTPO treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet fuction | Platelet aggregation function assay and the expression of P selectin on platelet surface | From randomization to 28 days after rhTPO/Herombopag/Herombopag+rhTPO treatment | 
| the markers of thrombosis and fibrinolysis | platelet-derived microparticals in plasma, concentration of Plasminogen Activator Inhibitor-1 （PAI-1）, D-D dimer, tissue plasminogen activator （tPA），urokinase-type plasminogen activator （uPA） and Thrombin activatable fibrinolysis inhibitor （TAFI） | From randomization to 28 days after rhTPO/Herombopag/Herombopag+rhTPO treatment | 
| Thrombotic events | the number/time/site of thrombotic events （lower extremity deep vein thrombosis, pulmonary embolism, intracranial thrombosis, .etc）in participants | From randomization to 3 months after rhTPO/Herombopag/Herombopag+rhTPO treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
immune thrombocytopenia, severe, Herombopag, recombinant human thrombopoietin