Efficacy and Safety of Herombopag in Patients With Thrombocytopenia Before Hepatectomy

Study Overview
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Brief Summary
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This is a single center, randomized, controlled study, to evaluate the efficacy and safety of Herombopag in patients with Thrombocytopenia before hepatectomy.

Detailed Description
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The purpose of this study is to assess the ability of Herombopag to elevate platelet counts thereby reducing the need for platelet transfusions in patients with thrombocytopenia before hepatectomy. The clinical benefit of Herombopag will be measured by the proportion of subjects who avoid platelet transfusions, before, during and up to 7 days after undergoing an hepatectomy. In addition, bleeding events will be monitored during this time. The number of transfusions, safety events will be monitored during this time and for up to 3 months after undergoing a hepatectomy to help further evaluate clinical benefit.

Official Title
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Director, Department of Liver Surgery, Fudan University Shanghai Cancer Center

Conditions
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Hepatopathy

Intervention / Treatment
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* Drug: Hetrombopag
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Male and female subjects ≥18 years of age； 2.Patients prepared to receive hepatectomy； 3.50×10^9/L≤platelet count≤100×10^9/L； 4.Child-PUgh score A or grade B (≤7 )； 5.Life expectancy ≥3 months； 6.Normal Bone marrow hematopoiesis and renal function; 7.Voluntary participation and written informed consent; Exclusion Criteria: 1.Central nervous system diseases caused by liver disease; 2.Platelet transfusion within 7 days prior to the first dose of study drug; 3.History of any primary hematologic disorder; 4.History of arterial or venous thrombosis, including thrombosis of any part of the splenic-mesenteric system; 5.Pre-diagnosed Immune Thrombocytopenic Purpura (ITP); 6.History of Myelodysplastic Syndrome (MDS); 7.Those with bleeding tendency，have evidence of hereditary bleeding or blood coagulation disorder; 8.Females who are pregnant (positive β-hCG test ) or breastfeeding; 9.Subjects who have participated in another investigational trial within 30 days prior to Visit 1; 10.Those with uncontrollable neurological and psychiatric diseases or mental disorders, poor compliance, unable to cooperate and describe treatment response; 11.Subjects with known intolerance or allergy to any of the ingredients in eltrombopag tablets;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: 1<br>durg：Hetrombopag 5mg，once daily，oral | Drug: Hetrombopag<br>* The patients received Hetrombopag 5mg orally d1-14 days, surgery will be conducted at d6-14 day<br>|
| Experimental: Experimental: 2<br>Ndurg： Placebo 5mg，once daily，oral | Drug: Placebo<br>* The patients received Placebo 5mg orally d1-14 days, surgery will be conducted at d6-14 day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients need perioperative platelet transfusions. | Platelet transfusions were administered at the discretion of the investigator and the physician performing the hepatectomy. | Prior to 5 days up to 14 days following surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with bleeding after surgery need intervention. | The World Health Organization Bleeding Scale was used to assess bleeding following surgery.. The range of possible scores is 0 to 4. Grade 0 is no bleeding; Grade 1 is petechiae (small [1-2 millimeter] red or purple spot on the body, caused by a minor hemorrhage); Grade 2 is mild blood loss; Grade 3 is gross blood loss (requiring a transfusion; and Grade 4 is debilitating blood loss (retinal or cerebral associated with fatality). | up to 7 days following surgery。 | 
| Prothrombin time、Activated partial thromboplastin time Change from baseline to prior to surgery | Prothrombin time、Activated partial thromboplastin time were determined from blood draws and collected on baseline and prior to 1 days of surgery. | baseline and up to 1 days prior to surgery | 
| Proportion of patients whose Platelet count returned to ≥100×10^9/L | Platelet count were determined from blood draws. platelet count collect on baseline and prior to 1 days of surgery. Missing platelet count assessments at any given time point was considered to be a non-response at that point and were not estimated. | baseline and up to 1 days prior to surgery | 
| Mean platelet volume change from baseline to prior to surgery. | platelet volume were determined from blood draws, and collected on baseline and prior to 1 days of surgery. | baseline and up to 1 days prior to surgery | 
| Incidence of deep venous thrombosis | Imaging examination will be conducted at d1、d3、d5、d7、d14、end of one month、 end of three month after surgery, to evaluate deep venous thrombosis if necessary. | up to 3 months following surgery. | 
| Incidence of liver failure | Posthepatectomy liver failure is defined as: A postoperatively acquired deterioration in the ability of the liver to maintain its synthetic, excretory, and detoxifying functions, characterized by an increased international normalized ratio A postoperatively acquired deterioration in the ability of the liver to maintain its synthetic, excretory, and detoxifying functions, characterized by an increased international normalized ratio and hyperbilirubinemia on or after postoperative day 5. If international normalized ratio or serum bilirubin concentration is increased preoperatively, Post hepatectomy liver failure is defined by an increasing international normalized ratio and increasing serum bilirubin concentration on or after postoperative day 5 Other obvious causes for the observed biochemical and clinical alterations such as biliary obstruction should be ruled out. The evaluate of liver failure was conducted at d1、d3、d5、d7、d14、end of one month、 end of three month after surgery. | up to 3 months following surgery. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatopathy, thrombocytopenia, Hetrombopag