Efficacy of Avatrombopag in Thrombocytopenic Patients With Chronic Liver Disease Undergoing an Elective Procedure

NCT04915287 | Unknown Phase 4 FDA Drug

• 1 other identifier: S2021-240-02
• Study Type: interventional
• Target: 476
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, investigators aimed to evaluate the efficacy of Avatrombopag in thrombocytopenic patients with chronic liver disease undergoing an elective invasive procedure through a prospective, non-randomized controlled, multicenter clinical trial. The patients were non-randomly assigned to the Avatrombopag group (119 patients) and the conventional treatment group (357 patients). The primary endpoint was the proportion of patients not requiring prophylactic platelet transfusion or rescue therapy due to bleeding from grouping up to 10 days post-procedure. Second endpoints included the proportion of patients achieving a platelet count of ≥50x10\^9/L and the mean change in platelet count from baseline at the time before the procedure, the proportion of patients requiring platelet transfusion and the mean platelet transfusion units per capita, the incidence of bleeding events (WHO≥2 and requiring rescue therapy), the imaging evaluations of bleeding events, the incidence of adverse events, the changes in life quality between two groups before and after treatment, and the pharmacoeconomic index of two groups. Note: According to the results of interim statistical analysis (200-300 cases), it is up to the sponsor to decide whether to terminate the study in advance or increase the number of included cases at a later stage.

Conditions

Thrombocytopenia; Drugs; Chronic Liver Disease

Keywords

Thrombocytopenia; Chronic Liver Disease; Avatrombopag; Invasive procedure

Outcome Measures

Primary Outcomes (2)

• The proportion of patients not requiring prophylactic platelet transfusion

  The proportion of patients not requiring prophylactic platelet transfusion

  From grouping up to 10 days post-procedure

• The proportion of patients not requiring rescue therapy due to bleeding

  The proportion of patients not requiring rescue therapy due to bleeding

  From grouping up to 10 days post-procedure

Secondary Outcomes (9)

• The proportion of patients achieving a platelet count of ≥50x10^9/L

  The time before the procedure in the procedure day

• The mean change in platelet count from baseline

  The time before the procedure in the procedure day

• The proportion of patients requiring platelet transfusion

  From grouping up to 10 days post-procedure

• The mean platelet transfusion units per capital

  From grouping up to 10 days post-procedure

• The incidence of bleeding events

  From grouping up to 10 days post-procedure

Study Arms (2)

Avatrombopag

EXPERIMENTAL

Oral administration of Avatrombopag Maleate Tablets to the thrombocytopenic patients with chronic liver disease undergoing an elective procedure whose mean baseline platelet count is less than 50 × 10\^9/L. RhuTPO, rhIL-11, Romiplostim, Eltrombopag, or Lusutrombopag, etc., are prohibited during the trial.

Drug: Avatrombopag maleate

Conventional treatment

EXPERIMENTAL

Conventional treatment (platelet transfusion if needed or rhuTPO, rhIL-11, Romiplostim, Eltrombopag, or Lusutrombopag, etc.) to the thrombocytopenic patients with chronic liver disease undergoing an elective procedure whoes mean baseline platelet count is less than 50 × 10\^9/L.

Biological: Platelet transfusion; Drug: Medicine

Interventions

Avatrombopag maleate DRUG

1. Mean baseline platelet count 40 to less than 50 × 10\^9/L: 40mg Avatrombopag QD × 5 days from 10-13 days pre-procedure 2. Mean baseline platelet count less than 40 × 10\^9/L: 60mg Avatrombopag QD × 5 days from 10-13 days pre-procedure

Also known as: Doptelet

Avatrombopag

Platelet transfusion BIOLOGICAL

Mean baseline platelet count less than 50 × 10\^9/L pre-procedure: platelet transfusion if needed

Conventional treatment

Medicine DRUG

Mean baseline platelet count less than 50 × 10\^9/L pre-procedure: rhuTPO, rhIL-11, Romiplostim, Eltrombopag, or Lusutrombopag, etc.

Also known as: Other drugs

Conventional treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Both men and women are at least 18 years old at the time of signing the informed consent;
• Baseline platelet count\<50×10\^9/L;
• Patients with chronic liver disease undergo elective invasive procedures with high bleeding risk. The invasive procedures include liver/kidney biopsy or ablation, biliary drainage/stent implantation, cholecystostomy, transjugular intrahepatic portal venous shunt, nephrostomy and catheterization, chemotherapy embolization, abdominal/pelvic/retroperitoneal/mediastinal biopsy or ablation, endoscopic polypectomy, endoscopic stricture dilation or mucosal resection, balloon-assisted enteroscopy, percutaneous endoscopic gastrostomy, endoscopic retrograde cholangiopancreatography with sphincterotomy (ERCP + EST), endoscopic ultrasound with fine-needle aspiration (EUS-FNA), cyst gastrostomy, dental extraction, angiography or interventional venography and therapeutic coronary angiography such as PCI), and intraarticular injection, etc.;
• Be able to understand the study and is willing to follow all study procedures, and voluntarily sign informed consent before screening;
• According to the opinions of the researchers, it can meet the requirements of this study.

You may not qualify if:

• Subjects with a history of arterial or venous thrombosis within six months before baseline;
• Subjects with a known history of the hereditary prethrombotic syndrome include thrombin factor V Leiden mutation, prothrombin G20210A mutation, or hereditary antithrombin III (ATIII) deficiency;
• Subjects could not suspend anticoagulants or antiplatelet therapy within one week preoperatively, such as heparin (within 24 hours before the procedure for Low molecular weight heparin), warfarin, rivaroxaban, dipyridamole, non-steroidal anti-inflammatory drugs, aspirin, verapamil, ticlopidine, clopidogrel, glycoprotein IIb/IIIa antagonists, and erythropoietin, etc.;
• Subjects could not suspend Chinese patent medicines within three days before the procedure to promote blood circulation and remove blood stasis, such as pseudo-ginseng, red-rooted salvia, etc.;
• Subjects received thrombopoietin receptor agonists within two weeks before enrolment, such as rhuTPO, Romiplostim, Eltrombopag, Avatrombopag, or Lusutrombopag, etc. Subjects received rhIL-11 within two weeks before enrolment. Moreover, subjects received platelet transfusion within one week before enrolment;
• Subjects with thrombocytopenia caused by primary blood diseases (immune thrombocytopenia, myelodysplastic syndrome, etc.) or drugs (such as chemotherapy drugs, targeted therapy drugs, immune checkpoint inhibitors, etc.). Exceptions: Subjects are allowed to receive targeted drugs that do not cause thrombocytopenia, provided that these targeted therapy drugs are discontinued for a while to reduce the risk of bleeding, as follows: Bevacizumab for four weeks (6 weeks for patients with coagulation abnormality), lumvaritinib, sorafenib, pazopanib, axitinib, cabozantinib, anlotinib, apatinib, nidanib, and sunitinib for one week, and fuquanitinib for two weeks, etc.;
• Subjects scheduled for splenic embolization (excluding those with persistent low platelet counts after splenic embolization or splenectomy);
• Concomitant medical histories (e.g., gastrointestinal bleeding within three months; high risk of thrombosis, e.g., portal vein blood flow velocity \< 10cm/s) may prevent subjects from completing the study safely;
• Subjects are allergic to avatrombopag or any of its excipients;
• A woman who is pregnant or who intends to become pregnant;
• Subjects participate in another clinical study using any exploratory drug or device within 30 days before their baseline visit; Participation in observational studies is permitted;
• The investigator considers that any accompanying medical history of the subject may affect the subject's ability to complete the study safely.

Sponsors & Collaborators

• Chinese PLA General Hospital: lead

Study Sites (1)

Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

RECRUITING

MeSH Terms

Conditions

Thrombocytopenia

Interventions

avatrombopag; Platelet Transfusion; Dosage Forms

Condition Hierarchy (Ancestors)

Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia

Intervention Hierarchy (Ancestors)

Blood Component Transfusion; Blood Transfusion; Biological Therapy; Therapeutics; Pharmaceutical Preparations; Technology, Pharmaceutical; Investigative Techniques

Study Officials

• Ping Liang, Doctor

  Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shuilian Tan, Master

CONTACT

15910606696; 15910606696@163.com

Fan Xiao, Doctor

CONTACT

13576071526; short19860526@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician

Study Record Dates

• First Submitted: May 23, 2021
• First Posted: June 7, 2021
• Study Start: June 6, 2021
• Primary Completion: June 30, 2023
• Study Completion: July 31, 2023
• Last Updated: November 15, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)