Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia

The Efficacy and Safety of Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia: A Multicenter, Prospective, Randomized Controlled Trial（EAST）

End stage liver disease is prone to thrombocytopenia. This study is a multi-center, randomized, prospective, randomized controlled Phase IV Clinical trial to discuss the Efficacy and Safety of Avatrombopag in Patients with End-stage Liver Disease and Thrombocytopenia.

Study Overview

• Status: Recruiting
• Conditions: Liver Failure; Decompensated Cirrhosis; Thrombocytopenia
• Intervention / Treatment: Drug: Avatrombopag; Drug: Standard medical treatment

Detailed Description

End stage liver disease is prone to thrombocytopenia. This study aims to discuss the Efficacy and Safety of Avatrombopag in Patients with End-stage Liver Disease and Thrombocytopenia in a multicenter, prospective, randomized controlled trial. The patients were divided into one of the groups according to if receiving avatrombopag. Avatrombopag was taken to maintain platelet count 50~100×10^9/L. Starting dose is recommended according to the patient's baseline platelet count level. Routine treatment was taken in the Control group and Interventional group. This trial will take about 2 to 2.5 years from the first participant signing an informed consent form (ICF) until all study-related telephone follow-ups or visits end.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Qin Ning, MD., PhD.; Phone Number: +8602783662391; Email: qning@vip.sina.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Recruiting
      • Department of infectious disease, Tongji Hospital
      • Contact: Qin Ning; Phone Number: +8602783662391; Email: qning@vip.sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men and women greater than or equal to 18 years of age;
2. Baseline platelet count <50×10^9/L;
3. End-stage liver disease, including acute-on-chronic liver failure, acute decompensation of liver cirrhosis, chronic liver failure;
4. Women of childbearing potential must agree to use a highly effective method of contraception from the beginning of Baseline Visit until the end of treatment (includes implantable contraception, injectable contraception, hormonal combination contraception [including vaginal rings], intra-uterine devices or vasectomy). The barrier contraception with or without spermicide alone, double barrier contraception and oral contraceptives are inadequate;
5. Subject is able to understand the study and willing to follow the protocol and sign informed consent voluntarily before Baseline Visit;
6. Subject meet the criteria according to the opinion of the researchers.

Exclusion Criteria:

1. Subject has a history of arterial or venous thrombosis within the previous 6 months of baseline;
2. Known portal vein blood flow velocity rate <10 cm/second or previous occurrence of a portal vein thrombosis within 6 months of Baseline;
3. Known any history of primary blood (e.g, immune thrombocytopenia, myelodysplastic syndrome, aplastic anemia);
4. Subject has a known medical history of genetic prothrombotic syndromes (e.g, Factor V Leiden prothrombin G20210A, antithrombin III (AT III) deficiency);
5. Subject has a recent history (within the previous 6 months) of significant cardiovascular diseases (e.g., exacerbation of congestive heart failure, arrhythmias known to increase the risk of thromboembolic events [e.g. atrial fibrillation], coronary or peripheral artery stent placement or angioplasty, and coronary or peripheral artery bypass grafting);
6. Female subjects who are lactating or pregnant at the Baseline Visit (as documented by a positive serum beta-human chorionic gonadotropin [β-hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of β-hCG) or are planning to become pregnant during the study;
7. The subject has a hypersensitivity to Avatrombopag or any of its excipients;
8. Subjects with drug-induced thrombocytopenia;
9. Subjects whose Life expectation ≤6 months;
10. Subject with a current malignancy;
11. Subjects with HIV infection;
12. At screening, active infection was not effectively controlled by systemic antibiotic therapy;
13. The Investigator believe that any accompanying medical history may affect the safety of the subjects to complete the study;
14. The Investigator believe that there are any other factors that are not suitable for inclusion or affect participation or completion of the study;
15. Subject is enrolled in another clinical study with any investigational drug or device within previous 30 days of the Baseline Visit, but are allowed to participate in observational studies.

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: Intervention group; Avatrombopag+Standard medical treatment	Drug: Avatrombopag; Avatrombopag: PLT：30~50×10^9/L patients, 40 mg/d; PLT：<30×10^9/L patients, 60 mg/d.; Drug: Standard medical treatment; Standard medical treatment included transmetil, compound glycyrrhizinate, reduced glutathione and hepatocyte growth factor, et. al.; Other Names: transmetil, compound glycyrrhizinate, reduced glutathione and hepatocyte growth factor, et. al.
Other: Control group; Standard medical treatment	Drug: Standard medical treatment; Standard medical treatment included transmetil, compound glycyrrhizinate, reduced glutathione and hepatocyte growth factor, et. al.; Other Names: transmetil, compound glycyrrhizinate, reduced glutathione and hepatocyte growth factor, et. al.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet count response time	Platelet count response time(PLT) refers to condition of PLT during 24 weeks between the Intervention group and Control group.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event (thrombotic events, bleeding events, etc.) incidence;	Adverse Event refers to the incidence rate of adverse event between the two groups during 24 weeks	24 weeks
Incidence of complications of liver cirrhosis (infection, etc.)	Incidence of complications of liver cirrhosis refers to the incidence rate of complications between the two groups during 24 weeks	24 weeks
Patients without platelet transfusion or rescue due to bleeding	Patients without platelet transfusion or rescue due to bleeding refers to the patients rate without platelet transfusion or rescue due to bleeding between the two groups at 24 week	24 weeks
Proportion of patients readmitted	Proportion of patients readmitted refers to the readmission rate within 24 weeks between the Intervention group and Control group	24 weeks
Changes in total bilirubin level	Changes in total bilirubin level refers to the changes of total bilirubin at 24 week compared to baseline between the Intervention group and Control group.	24 weeks
Changes in alanine aminotransferase level	Changes in alanine aminotransferase level refers to the changes of alanine aminotransferase at 24 week compared to baseline between the Intervention group and Control group.	24 weeks
Changes in albumin level	Changes in albumin level refers to the changes of albumin at 24 week compared to baseline between the Intervention group and Control group.	24 weeks
Changes in prothrombin time level	Changes in prothrombin time level refers to the changes of prothrombin time at 24 week compared to baseline between the Intervention group and Control group.	24 weeks
Changes in international normalized ratio level	Changes in international normalized ratio level refers to the changes of international normalized ratio at 24 week compared to baseline between the Intervention group and Control group.	24 weeks

Collaborators and Investigators

• Sponsor: Tongji Hospital
• Collaborators: The First Affiliated Hospital of Nanchang University; The First Hospital of Jilin University; Anhui Provincial Hospital; Taihe Hospital, Hubei University of Medicine
• Investigators: Study Chair: Qin Ning, MD., PhD., Department of Infectious Disease, Tongji Hospital, Tongji Medical College, HUST

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: May 17, 2021
• First Submitted That Met QC Criteria: May 26, 2021
• First Posted (Actual): May 28, 2021

Study Record Updates

• Last Update Posted (Actual): June 7, 2021
• Last Update Submitted That Met QC Criteria: June 3, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: safety; efficacy; end-stage liver disease; thrombocytopenia; avatrombopag
• Additional Relevant MeSH Terms: Digestive System Diseases; Hepatic Insufficiency; Hematologic Diseases; Blood Platelet Disorders; Liver Diseases; End Stage Liver Disease; Liver Failure; Thrombocytopenia; Molecular Mechanisms of Pharmacological Action; Mitosis Modulators; Mitogens
• Other Study ID Numbers: TJ20210517

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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