Herombopag + rhTPO in Severe Immune Thrombocytopenia

Phase 3

• Conditions: Immune Thrombocytopenia
• Interventions: Drug: rhTPO; Drug: Herombopag

• Registration Number: NCT05328804
• Lead Sponsor: Yin Jie

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.

Study Timeline

• Study Start: 2022-01-01
• Status Verified: 2022-04
• Study First Submitted: 2022-04-06
• Study First Submitted QC: 2022-04-13
• Study First Posted: 2022-04-14
• Last Update Submitted: 2022-04-19
• Last Update Posted: 2022-04-26
• Primary Completion: 2023-11-30
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

1. Male or female,70 ≥age≥18；
2. Diagnosed as primary immune thrombocytopenia；
3. Platelet count was less than 10 × 10E9 / L with active bleeding, or bleeding score ≥ 5 points；
4. No use of IVIG, Avatrombopag, Eltrombopag or Romiplostim 2 weeks before treatment；
5. Rituximab was used for at least 2 months, and other immunosuppressants were stable for at least 4 weeks.
6. There was no history of platelet transfusion one week before treatment.

Exclusion Criteria

1. Secondary thrombocytopenia caused by other autoimmune diseases and virus infection was excluded；
2. Patients with active malignant tumors, pregnancy, severe cardiovascular， cerebrovascular diseases and a history of arteriovenous thrombotic diseases were excluded；
3. Patients deemed unsuitable for enrollment by the investigator；
4. Patients with thrombotic disease or serious uncontrolled cardiovascular and cerebrovascular disease;
5. Patients reject to participate in the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
rhTPO	rhTPO	rhTPO will be injected subcutaneously at 300 u/kg daily for 14 days.
Herombopag	Herombopag	Herombopag will be taken orally at 5 mg daily for 28 days.
Herombopag in combination of rhTPO	rhTPO	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
Herombopag in combination of rhTPO	Herombopag	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

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
the markers of thrombosis and fibrinolysis	From randomization to 28 days after rhTPO/Herombopag/Herombopag+rhTPO treatment	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）
Platelet fuction	From randomization to 28 days after rhTPO/Herombopag/Herombopag+rhTPO treatment	Platelet aggregation function assay and the expression of P selectin on platelet surface
Thrombotic events	From randomization to 3 months after rhTPO/Herombopag/Herombopag+rhTPO treatment	the number/time/site of thrombotic events （lower extremity deep vein thrombosis, pulmonary embolism, intracranial thrombosis, .etc）in participants

Trial Locations

Locations (1)

Jie Yin; 🇨🇳 Suzhou, Jiangsu, China