Clinical trial NCT05087459: Treatment of Avatrombopag for Thrombocytopenia in Patients Undergoing Selective Resection of Hepatocellular Carcinoma
Official title: Efficacy and Safety of Avatrombopag in Thrombocytopenia in Patients With Primary Hepatocellular Carcinoma Undergoing Elective Hepatectomy: a Multicenter, Randomized, Controlled Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Thrombocytopenia
Keywords: Avatrombopag
Primary hepatocellular carcinoma
elective hepatectomy
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
First posted: 2021-10-21
Enrollment: 141
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Elective hepatectomy with thrombocytopenia in adults with primary hepatocellular carcinoma

Brief summary: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, accounting for the second leading cause of cancer death in China.Surgical treatment of hepatocellular carcinoma is the most important means for long-term survival of patients with hepatocellular carcinoma, including hepatectomy and liver transplantation.Chronic liver disease caused by hepatitis B infection is the main pathogenic factor of liver cancer in China. Meanwhile, nearly 80% of patients with hepatocellular carcinoma are complicated with cirrhosis, and the incidence of thrombocytopenia in patients with cirrhosis is reported to be as high as 78%.Many previous studies have found that thrombocytopenia is closely related to perioperative outcome of hepatocellular carcinoma.The purpose of this study was to evaluate the efficacy and safety of avatripopa in the treatment of thrombocytopenia in patients with primary hepatocellular carcinoma undergoing elective hepatectomy and its effect on perioperative outcome.

Detailed description: The indicators included changes in platelet count before and after drug treatment and operation, the nature and amount of postoperative drainage (ascites), duration of indwelling drainage tube, intraoperative blood loss, perioperative complications, length of hospital stay, etc.After comprehensive consideration of all perioperative indicators, we selected the total amount of drainage (ascites) multiple days after surgery as the primary outcome.

Eligibility criteria: Inclusion Criteria:

1. Be able to understand this study and be willing to abide by all research procedures and sign informed consent voluntarily before screening;
2. Male or female, at least 18 years old when signing informed consent;
3. The initial clinical diagnosis of hepatocellular carcinoma was confirmed, and the CNLC stages were IA and IB;
4. Before enrollment, baseline platelet count \< 75×10\^9/L and \> 30×10\^9/L;
5. Elective hepatectomy is proposed, including laparotomy or laparoscopic hepatectomy, except hepatectomy combined with splenectomy or radiofrequency ablation;
6. Child-pugh GRADE A;
7. HBsAg and/or anti-HCV positive;
8. Male patients who are infertile or who agree to use appropriate contraceptive methods from the beginning of screening until the completion of the post-treatment phase;
9. Women who have not undergone menopause or surgical sterilization need to agree to use highly effective contraception from the beginning of screening until the completion of the post-treatment phase;
10. According to the opinions of researchers, those who can meet the requirements of this study.

Exclusion Criteria:

1. Any diseases below: Solid malignancies other than hepatocellular carcinoma, blood system tumor, aplastic anemia, myelodysplastic syndrome, myelofibrosis, congenital thrombocytopenia, drug-induced thrombocytopenia, immune thrombocytopenia, need treatment of systemic infection (except viral hepatitis);
2. Always thrombosis or current or former state (such as cerebral infarction, myocardial infarction, angina pectoris, coronary artery carotid stenting and angioplasty, coronary artery bypass grafting, congestive heart failure, known to increase the risk of thromboembolic events of arrhythmias such as atrial fibrillation, pulmonary thromboembolism, deep vein thrombosis or diffuse intravascular coagulation syndrome).
3. A known history of hereditary prethrombotic syndrome (e.g., clotting factor V Leiden mutation, prothrombin G20210A mutation, or hereditary antithrombin III (ATIII) deficiency);
4. Transfusion of platelets or blood products containing platelets within 7 days prior to screening;
5. Use erythropoietin within 7 days before screening;
6. Rhil-11,rhTPO, TPO receptor agonists (such as Avatriprap, altrippal, or romistetine) or splenic embolization within 30 days prior to screening;
7. Use of any of the following drugs or treatments within 90 days prior to screening: chemotherapy, interferon preparations, radiation;
8. Patients requiring systemic chemotherapy, targeted therapy, immunotherapy, traditional Chinese herbal therapy or radiation therapy during the study period;
9. At screening time, hemoglobin level ≤9.0g/dL or ≥18.0g/dL in male patients and \> 15.0g/dL in female patients, and hematocrit in male ≥0.54 and female ≥0.45;
10. Bleeding score ≥2 at screening (according to the WHO Bleeding scale);
11. Pt-inr and APTT at screening were lower than 80% of the lower limit of normal range or higher than 120% of the upper limit of normal range;
12. Preoperative anticoagulant or antiplatelet therapy should not be suspended according to the standard (low-dose aspirin is allowed to continue);
13. Female subjects who are breast-feeding or pregnant at the time of screening, or who plan to become pregnant during the study period;
14. Known or suspected persistent alcohol or drug abuse;
15. Known allergy to Avatripopa or any of its excipients;
16. HIV infected persons;
17. Participate in another clinical study within 30 days prior to screening, using any exploratory drugs or devices;Allowed to participate in observational studies;
18. The investigator believes that the accompanying medical history may affect the subjects' safe completion of the study;
19. In the opinion of the investigator, there are any other factors that may not be suitable for inclusion or affect participation or completion of the study.

Primary outcomes:
measure: Percentage of patients with a platelet count ≥75×10^9/L and an increase of platelet count more than 20% from baseline
timeFrame: on day 9-12 of treatment
measure: Comparison of total amount of postoperative drainage fluid between treatment group and control group
timeFrame: on day 1-5 after surgery
Secondary outcomes:
measure: Comparison of intraoperative blood loss
timeFrame: During surgery
measure: Proportion of patients receiving remedial treatment due to bleeding risk after surgery
timeFrame: on day 0-30 after surgery
measure: Indwelling time of drainage tube
timeFrame: on day 0-10 after surgery
measure: Red blood cell count and hemoglobin content of drainage fluid
timeFrame: on day 1-5 after surgery
measure: Postoperative hospitalization time
timeFrame: on 0-30 day after surgery
measure: Preoperative platelet count increase from baseline
timeFrame: before surgery
measure: The change of platelet count from baseline at different time points
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhongshan hospital, Fudan University
Study officials:
affiliation: Fudan University
name: Jian Zhou, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Miller JB, Figueroa EJ, Haug RM, Shah NL. Thrombocytopenia in Chronic Liver Disease and the Role of Thrombopoietin Agonists. Gastroenterol Hepatol (N Y). 2019 Jun;15(6):326-332.
citation: Li J, Han B, Li H, Deng H, Mendez-Sanchez N, Guo X, Qi X. Association of coagulopathy with the risk of bleeding after invasive procedures in liver cirrhosis. Saudi J Gastroenterol. 2018 Jul-Aug;24(4):220-227. doi: 10.4103/sjg.SJG_486_17.