Treatment of Thrombocytopenia in Patients With Chronic Liver DiseaseUndergoing an Elective Procedure

Last updated: January 29, 2018
Sponsor: Eisai Inc.
Overall Status: Completed

Phase

3

Condition

Primary Biliary Cholangitis

White Cell Disorders

Platelet Disorders

Treatment

N/A

Clinical Study ID

NCT01972529
E5501-G000-310
2013-000965-34
  • Ages > 18
  • All Genders

Study Summary

This is a global, multicenter, randomized, double-blind, placebo-controlled, parallel group study using avatrombopag to treat adults with thrombocytopenia associated with liver disease. The study will evaluate avatrombopag in the treatment of thrombocytopenia associated with liver disease prior to an elective procedure to reduce the need for platelet transfusions or any rescue procedure for bleeding due to procedural and post-procedural bleeding complications. Participants will be enrolled into 2 cohorts according to mean baseline platelet count and, within each baseline platelet count cohort will be further stratified by risk of bleeding associated with the elective procedure (low, moderate, or high) and hepatocellular carcinoma (HCC) status (Yes or No).

Eligibility Criteria

Inclusion

Inclusion Criteria

  1. Participants greater than or equal to 18 years of age at Screening with chronic liver disease

  2. Participants who have a mean baseline platelet count of less than 50 x 10^9/L. Platelet counts must be measured on 2 separate occasions, during the Screening Period and at Baseline, and must be performed at least one day apart with neither platelet count greater than 60 x 10^9/L. The mean of these 2 platelet counts (mean baseline platelet count) will be used for entry criteria and for assignment to the low or high baseline platelet count cohort.

  3. Participants scheduled to undergo a permitted elective procedure who, in the opinion of the investigator, will require a platelet transfusion to address a risk of bleeding associated with the procedure unless there is a clinically significant increase in platelet count from baseline

  4. Model For End-stage Liver Disease (MELD) score less than or equal to 24 at Screening

  5. If taking inhibitors of P glycoprotein (P-gp), except for verapamil, dose must be stable for 7 days prior to Screening

  6. Provide written informed consent

  7. Willing and able to comply with all aspects of the protocol

Exclusion Criteria

  1. Any history of arterial or venous thrombosis, including partial or complete thrombosis

  2. Evidence of thrombosis (partial or complete) in the main portal vein, portal vein branches, or any part of the splenic mesenteric system at Screening

  3. Portal vein blood flow velocity rate <10 centimeters/second at Screening

  4. Hepatic encephalopathy that cannot be effectively treated

  5. Participants with HCC with Barcelona Clinic Liver Cancer (BCLC) staging classification C or D

  6. Platelet transfusion or receipt of blood products containing platelets within 7 days of Screening. However packed red blood cells are permitted.

  7. Heparin, warfarin, nonsteroidal anti-inflammatory drugs (NSAID), aspirin, verapamil, and antiplatelet therapy with ticlopidine or glycoprotein IIb/IIIa antagonists (eg, tirofiban) within 7 days of Screening

  8. Use of erythropoietin stimulating agents within 7 days of Screening

  9. Interferon (IFN) use within 14 days of Screening

  10. Estrogen-containing hormonal contraceptive or hormone replacement therapy use within 30 days of Screening

  11. Active infection requiring systemic antibiotic therapy within 7 days of Screening. However, prophylactic use of antibiotics is permitted.

  12. Alcohol abuse, alcohol dependence syndrome, drug abuse, or drug dependence within 6 months of the study start (unless participating in a controlled rehabilitation program) or acute alcoholic hepatitis (chronic alcoholic hepatitis is allowed) within 6 months of the study start

  13. Elective procedure performed prior to Visit 4 (Procedure Day)

  14. Known to be human immunodeficiency virus positive

  15. Any clinically significant acute or active bleeding (eg, gastrointestinal, central nervous system)

  16. Known history of any primary hematologic disorder (eg, immune thrombocytopenic purpura, myelodysplastic syndrome)

  17. Known medical history of genetic prothrombotic syndromes (eg, Factor V Leiden; prothrombin G20210A; ATIII deficiency, etc.)

  18. Participants with a history of significant cardiovascular disease (eg, congestive heart failure New York Heart Association Grade III/IV, arrhythmia known to increase the risk of thromboembolic events [eg, atrial fibrillation], coronary artery stent placement, angioplasty, and coronary artery bypass grafting)

  19. Females of childbearing potential who have had unprotected sexual intercourse within 30 days before study entry and who do not agree to use a highly effective method of contraception (eg, total abstinence, an intrauterine device, a double-barrier method [such as condom plus diaphragm with spermicide], a progesterone-only contraceptive implant/injection, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation. If currently abstinent, the participant must agree to use a double-barrier method as described above if she becomes sexually active during the study period or for 30 days after study drug discontinuation. All females will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months consecutive amenorrhea in the appropriate age group and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, hysterectomy, or bilateral oophorectomy) at least 1 month before dosing.

  20. Females who are lactating or pregnant at Screening or Baseline (as documented by a positive serum beta-human chorionic gonadotropin [B-hCG] test with a minimum sensitivity 25 IU/L or equivalent units of B-hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.

  21. Post liver transplant participants

  22. Any participant who has previously received avatrombopag

  23. Hypersensitivity to avatrombopag maleate or any of its excipients

  24. Hemoglobin levels ≤ 8.0 or ≥ 18.0 g/dL for men and > 15 for women at Screening, with hematocrit ≥ 54% for men and ≥ 45% for women

  25. Current malignancy including solid tumors and hematologic malignancies (except HCC)

  26. Any history of concomitant medical condition that, in the opinion of the investigator(s), would compromise the participant's ability to safely complete the study

  27. Currently enrolled in another clinical trial with any investigational drug or device within 30 days of Screening

Study Design

Total Participants: 231
Study Start date:
February 01, 2014
Estimated Completion Date:
February 27, 2017

Study Description

This study will consist of 3 phases: Prerandomization, Randomization, and a Follow-up Phase. The Prerandomization Phase includes one Screening Visit that will take place from Day -14 through Day -1; the Randomization Phase includes the Baseline Period, Treatment Period, and Procedure Day Period (5 to 8 days after last dose of study drug [Study Day 10 to 13]). The Follow-up Phase comprises 2 visits: 7 days post Procedure Day and 30 days after receiving the last dose of study drug. Permitted procedures include: Paracentesis; Thoracentesis; Gastrointestinal endoscopy with or without plans for biopsy, colonoscopy, polypectomy, or variceal banding; Liver biopsy; Bronchoscopy with or without plans for biopsy; Ethanol ablation therapy or chemoembolization for HCC; Vascular catheterization (including right side procedures in participants with pulmonary hypertension); Transjugular intrahepatic portosystemic shunt; Dental procedures; Renal biopsy; Biliary interventions; Nephrostomy tube placement; Radiofrequency ablation; and Laparoscopic interventions.

Connect with a study center

  • Pilar, Buenos Aires
    Argentina

    Site Not Available

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    Ciudad Autonoma Bs As, Ciudad Autonoma Buenos Aires
    Argentina

    Site Not Available

  • Ciudad Autonoma Buenos Aires,
    Argentina

    Site Not Available

  • Mendoza,
    Argentina

    Site Not Available

  • Camperdown, New South Wales
    Australia

    Site Not Available

  • Adelaide, South Australia
    Australia

    Site Not Available

  • Bedford Park, South Australia
    Australia

    Site Not Available

  • Monash Institute of Medical Research

    Clayton, Victoria 3168
    Australia

    Site Not Available

  • Linz,
    Austria

    Site Not Available

  • Vienna,
    Austria

    Site Not Available

  • Wien,
    Austria

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  • Bruxelles,
    Belgium

    Site Not Available

  • Leuven,
    Belgium

    Site Not Available

  • Porto Alegre, Rio Grande Do Sul
    Brazil

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  • Sao Jose do Rio Preto, Sao Paulo
    Brazil

    Site Not Available

  • Sao Paulo,
    Brazil

    Site Not Available

  • London, Ontario
    Canada

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  • Toronto, Ontario
    Canada

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  • La Serena,
    Chile

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  • Santiago,
    Chile

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    Vina del Mar,
    Chile

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  • Changsha, Hunan
    China

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  • Nanjing, Jiangsu
    China

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  • Shanghai, Shanghai
    China

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  • Beijing,
    China

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  • Strasbourg, Bas Rhin
    France

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  • Grenoble cedex 9, Isere
    France

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  • Reims, Marne
    France

    Site Not Available

  • Clermont Ferrand cedex 1, Puy De Dome
    France

    Site Not Available

  • Amiens cedex 1, Somme
    France

    Site Not Available

  • Vandoeuvre les Nancy,
    France

    Site Not Available

  • Freiburg, Baden Wuerttemberg
    Germany

    Site Not Available

  • Klinikum der Johann Wolfgang Goethe-Universitaet

    Frankfurt, Hessen 60590
    Germany

    Site Not Available

  • Medizinische Hochschule Hannover

    Hannover, Niedersachsen 30625
    Germany

    Site Not Available

  • Universitaetsklinikum Bonn AoeR

    Bonn, Nordrhein Westfalen 53127
    Germany

    Site Not Available

  • Herne, Nordrhein Westfalen
    Germany

    Site Not Available

  • Koeln, Nordrhein Westfalen
    Germany

    Site Not Available

  • Kiel, Schleswig Holstein
    Germany

    Site Not Available

  • Hamburg,
    Germany

    Site Not Available

  • Bekescsaba,
    Hungary

    Site Not Available

  • Budapest,
    Hungary

    Site Not Available

  • Dunaujvaros,
    Hungary

    Site Not Available

  • Gyula,
    Hungary

    Site Not Available

  • Kaposvar,
    Hungary

    Site Not Available

  • Kecskemet,
    Hungary

    Site Not Available

  • Szombathely,
    Hungary

    Site Not Available

  • Zalaegerszeg,
    Hungary

    Site Not Available

  • San Giovanni Rotondo, Foggia
    Italy

    Site Not Available

  • Bari,
    Italy

    Site Not Available

  • Bologna,
    Italy

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  • Genova,
    Italy

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  • Milano,
    Italy

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  • Modena,
    Italy

    Site Not Available

  • Palermo,
    Italy

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  • Udine,
    Italy

    Site Not Available

  • Chuncheon, Gangwon-do
    Korea, Republic of

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    Chuncheon-si, Gangwon-do
    Korea, Republic of

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  • Guri-si, Gyeonggi-do
    Korea, Republic of

    Site Not Available

  • Seongnam-Si, Gyeonggi-do
    Korea, Republic of

    Site Not Available

  • Suwon, Gyeonggi-do
    Korea, Republic of

    Site Not Available

  • Yangsan, Gyeongnam
    Korea, Republic of

    Site Not Available

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    Yangsan-si, Gyeongnam
    Korea, Republic of

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  • Hwasun, Jeollanam-do
    Korea, Republic of

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    Hwasun-gun, Jeollanam-do
    Korea, Republic of

    Site Not Available

  • Busan,
    Korea, Republic of

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  • Daegu,
    Korea, Republic of

    Site Not Available

  • Incheon,
    Korea, Republic of

    Site Not Available

  • Seoul,
    Korea, Republic of

    Site Not Available

  • Katowice,
    Poland

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  • Lodz,
    Poland

    Site Not Available

  • Myslowice,
    Poland

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  • Szczecin,
    Poland

    Site Not Available

  • Wroclaw,
    Poland

    Site Not Available

  • Coimbra,
    Portugal

    Site Not Available

  • Lisboa,
    Portugal

    Site Not Available

  • Porto,
    Portugal

    Site Not Available

  • Viana do Castelo,
    Portugal

    Site Not Available

  • Vila Real,
    Portugal

    Site Not Available

  • Viseu,
    Portugal

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  • Barcelona,
    Spain

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  • Pontevedra,
    Spain

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  • Sevilla,
    Spain

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  • Valencia,
    Spain

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  • Valladolid,
    Spain

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  • Kaohsiung,
    Taiwan

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    Kaohsiung City,
    Taiwan

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  • Taichung,
    Taiwan

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    Taichung City,
    Taiwan

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  • Tainan,
    Taiwan

    Site Not Available

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    Tainan city,
    Taiwan

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  • Taipei,
    Taiwan

    Site Not Available

  • empty

    Taipei city,
    Taiwan

    Site Not Available

  • Taoyuan City,
    Taiwan

    Site Not Available

  • Bangkoknoi, Bangkok
    Thailand

    Site Not Available

  • Ratchathewi, Bangkok
    Thailand

    Site Not Available

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    Muang, Chiang Mai
    Thailand

    Site Not Available

  • Mueang Nonthaburi, Chiang Mai
    Thailand

    Site Not Available

  • Thammasat University Hospital

    Klongluang, Pathum Thani
    Thailand

    Site Not Available

  • Khlong Luang, Pathumthani
    Thailand

    Site Not Available

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    Klong Luang, Pathumthani
    Thailand

    Site Not Available

  • Truro, Cornwall
    United Kingdom

    Site Not Available

  • London, Greater London
    United Kingdom

    Site Not Available

  • Manchester, Greater Manchester
    United Kingdom

    Site Not Available

  • Wolverhampton, West Midlands
    United Kingdom

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  • Leeds, West Yorkshire
    United Kingdom

    Site Not Available

  • Lancaster, California
    United States

    Site Not Available

  • Long Beach, California
    United States

    Site Not Available

  • Los Angeles, California
    United States

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  • Sacramento, California
    United States

    Site Not Available

  • San Bernardino, California
    United States

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  • San Francisco, California
    United States

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  • Jacksonville, Florida
    United States

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  • Palmetto Bay, Florida
    United States

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  • Tampa, Florida
    United States

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  • New Orleans, Louisiana
    United States

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  • Rochester, Michigan
    United States

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  • Minneapolis, Minnesota
    United States

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  • Jackson, Mississippi
    United States

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  • Bronx, New York
    United States

    Site Not Available

  • Montefiore Medical Center PRIME

    Lake Success, New York
    United States

    Site Not Available

  • New York, New York
    United States

    Site Not Available

  • empty

    The Bronx, New York
    United States

    Site Not Available

  • Philadelphia, Pennsylvania
    United States

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  • Pittsburgh, Pennsylvania
    United States

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  • Dallas, Texas
    United States

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  • Harlingen, Texas
    United States

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  • Houston, Texas
    United States

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  • San Antonio, Texas
    United States

    Site Not Available

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