Clinical trial NCT04906083: Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia
Official title: The Efficacy and Safety of Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia: A Multicenter, Prospective, Randomized Controlled Trial（EAST）
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Liver Failure
Thrombocytopenia
Decompensated Cirrhosis
Keywords: end-stage liver disease
thrombocytopenia
avatrombopag
efficacy
safety
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
Collaborators: name: Anhui Provincial Hospital
name: The First Affiliated Hospital of Nanchang University
name: Taihe Hospital, Hubei University of Medicine
name: The First Hospital of Jilin University
First posted: 2021-05-28
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Platelet count response time
timeFrame: 24 weeks
Secondary outcomes:
measure: Adverse Event (thrombotic events, bleeding events, etc.) incidence;
timeFrame: 24 weeks
measure: Incidence of complications of liver cirrhosis (infection, etc.)
timeFrame: 24 weeks
measure: Patients without platelet transfusion or rescue due to bleeding
timeFrame: 24 weeks
measure: Proportion of patients readmitted
timeFrame: 24 weeks
measure: Changes in total bilirubin level
timeFrame: 24 weeks
measure: Changes in alanine aminotransferase level
timeFrame: 24 weeks
measure: Changes in albumin level
timeFrame: 24 weeks
measure: Changes in prothrombin time level
timeFrame: 24 weeks
measure: Changes in international normalized ratio level
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Department of infectious disease, Tongji Hospital
state: Hubei
Study officials:
affiliation: Department of Infectious Disease, Tongji Hospital, Tongji Medical College, HUST
name: Qin Ning, MD., PhD.
role: STUDY_CHAIR
References: