Treatment of Thrombocytopenia in Patients With Chronic Liver Disease Undergoing an Elective Procedure

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

Phase

3

Condition

Thrombosis

Platelet Disorders

Dysfunctional Uterine Bleeding

Treatment

N/A

Clinical Study ID

NCT01976104
E5501-G000-311
2013-000934-36
  • 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 subjects

  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: 204
Study Start date:
November 01, 2013
Estimated Completion Date:
February 21, 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

  • empty

    Quilmes, Buenos Aires
    Argentina

    Site Not Available

  • Ciudad Autonoma Buenos Aires,
    Argentina

    Site Not Available

  • Cordoba,
    Argentina

    Site Not Available

  • Rosario,
    Argentina

    Site Not Available

  • Clayton, Victoria
    Australia

    Site Not Available

  • Footscray, Victoria
    Australia

    Site Not Available

  • empty

    Heidelberg, Victoria
    Australia

    Site Not Available

  • Melbourne, Victoria
    Australia

    Site Not Available

  • Parkville, Victoria
    Australia

    Site Not Available

  • Edegem,
    Belgium

    Site Not Available

  • Gent,
    Belgium

    Site Not Available

  • Liege,
    Belgium

    Site Not Available

  • Aracaju,
    Brazil

    Site Not Available

  • Botucatu,
    Brazil

    Site Not Available

  • Porto Alegre,
    Brazil

    Site Not Available

  • Salvador,
    Brazil

    Site Not Available

  • empty

    Sao Paulo,
    Brazil

    Site Not Available

  • Calgary,
    Canada

    Site Not Available

  • Edmonton,
    Canada

    Site Not Available

  • Hefei, Anhui
    China

    Site Not Available

  • Beijing, Beijing
    China

    Site Not Available

  • empty

    Beijing, P.R., Beijing
    China

    Site Not Available

  • Shijiazhuang, Hebei
    China

    Site Not Available

  • Nanjing, Jiangsu
    China

    Site Not Available

  • Xi'an, Shanxi
    China

    Site Not Available

  • Chengdu, Sichuan
    China

    Site Not Available

  • Hangzhou, Zheijiang
    China

    Site Not Available

  • Brno,
    Czechia

    Site Not Available

  • Havirov,
    Czechia

    Site Not Available

  • Ostrava,
    Czechia

    Site Not Available

  • Praha 2,
    Czechia

    Site Not Available

  • Praha 4,
    Czechia

    Site Not Available

  • Usti nad Labem,
    Czechia

    Site Not Available

  • Nice Cedex 3, Alpes Maritimes
    France

    Site Not Available

  • Clichy cedex, Hauts De Seine
    France

    Site Not Available

  • Rennes cedex 09, Ille Et Vilaine
    France

    Site Not Available

  • Lyon Cedex 04, Rhone
    France

    Site Not Available

  • Villejuif, Val De Marne
    France

    Site Not Available

  • empty

    Creteil Cedex, Val de Marne
    France

    Site Not Available

  • empty

    Lyon,
    France

    Site Not Available

  • Mannheim, Baden Wuerttemberg
    Germany

    Site Not Available

  • Tuebingen, Baden Wuerttemberg
    Germany

    Site Not Available

  • Frankfurt, Hessen
    Germany

    Site Not Available

  • Hannover, Niedersachsen
    Germany

    Site Not Available

  • Bonn, Nordrhein Westfalen
    Germany

    Site Not Available

  • Leipzig, Sachsen
    Germany

    Site Not Available

  • Kiel, Schleswig Holstein
    Germany

    Site Not Available

  • Hamburg,
    Germany

    Site Not Available

  • empty

    Beer Yaakov,
    Israel

    Site Not Available

  • Haifa,
    Israel

    Site Not Available

  • Holon,
    Israel

    Site Not Available

  • Jerusalem,
    Israel

    Site Not Available

  • Nahariya,
    Israel

    Site Not Available

  • empty

    Nazareth, 16234
    Israel

    Site Not Available

  • Petach Tikva,
    Israel

    Site Not Available

  • Ramat-Gan,
    Israel

    Site Not Available

  • Rechovot,
    Israel

    Site Not Available

  • Ziv Medical Center

    Safed,
    Israel

    Site Not Available

  • Tel Aviv,
    Israel

    Site Not Available

  • Baggiovara, Modena
    Italy

    Site Not Available

  • empty

    Carpi, Modena
    Italy

    Site Not Available

  • empty

    Localita Baggiovara, Modena
    Italy

    Site Not Available

  • Firenze,
    Italy

    Site Not Available

  • Milano,
    Italy

    Site Not Available

  • Pisa,
    Italy

    Site Not Available

  • Roma,
    Italy

    Site Not Available

  • Trento,
    Italy

    Site Not Available

  • empty

    Chiba-shi, Chiba
    Japan

    Site Not Available

  • Sapporo-shi, Hokkaido
    Japan

    Site Not Available

  • Nishinomiya, Hyogo
    Japan

    Site Not Available

  • empty

    Nishinomiya-shi, Hyogo
    Japan

    Site Not Available

  • Morioka, Iwate
    Japan

    Site Not Available

  • empty

    Morioka-shi, Iwate
    Japan

    Site Not Available

  • Takamatsu, Kagawa
    Japan

    Site Not Available

  • empty

    Takamatsu-shi, Kagawa
    Japan

    Site Not Available

  • empty

    Niigata-shi, Niigata
    Japan

    Site Not Available

  • Yufu, Oita
    Japan

    Site Not Available

  • empty

    Yufu-shi, Oita
    Japan

    Site Not Available

  • Okayama-shi, Okayama
    Japan

    Site Not Available

  • Osaka-Sayama-shi, Osaka
    Japan

    Site Not Available

  • Osaka-shi, Osaka
    Japan

    Site Not Available

  • Iruma, Saitama
    Japan

    Site Not Available

  • empty

    Iruma-gun, Saitama
    Japan

    Site Not Available

  • empty

    Tokushima-shi, Tokushima
    Japan

    Site Not Available

  • Bunkyo-ku, Tokyo
    Japan

    Site Not Available

  • Chiyoda, Tokyo
    Japan

    Site Not Available

  • empty

    Chiyoda-ku, Tokyo
    Japan

    Site Not Available

  • Musashino, Tokyo
    Japan

    Site Not Available

  • empty

    Musashino-shi, Tokyo
    Japan

    Site Not Available

  • Setagaya-ku, Tokyo
    Japan

    Site Not Available

  • Shinagawa-ku, Tokyo
    Japan

    Site Not Available

  • empty

    Wakayama-shi, Wakayam
    Japan

    Site Not Available

  • Chiba,
    Japan

    Site Not Available

  • Niigata,
    Japan

    Site Not Available

  • Okayama,
    Japan

    Site Not Available

  • Tokushima,
    Japan

    Site Not Available

  • Wakayama,
    Japan

    Site Not Available

  • empty

    Mexico, Distrito Federal
    Mexico

    Site Not Available

  • empty

    El Salto, Jalisco
    Mexico

    Site Not Available

  • Zapopan, Jalisco
    Mexico

    Site Not Available

  • empty

    Zopopan, Jalisco
    Mexico

    Site Not Available

  • Monterrey, Nuevo León
    Mexico

    Site Not Available

  • empty

    Boca del Rio, Veracruz
    Mexico

    Site Not Available

  • Orizaba, Veracruz
    Mexico

    Site Not Available

  • Merida, Yucatán
    Mexico

    Site Not Available

  • Durango,
    Mexico

    Site Not Available

  • empty

    Mexico City,
    Mexico

    Site Not Available

  • Arad,
    Romania

    Site Not Available

  • Bucharest,
    Romania

    Site Not Available

  • Bucuresti,
    Romania

    Site Not Available

  • Craiova,
    Romania

    Site Not Available

  • Iasi,
    Romania

    Site Not Available

  • Sibiu,
    Romania

    Site Not Available

  • Timisoara,
    Romania

    Site Not Available

  • Kemerovo,
    Russian Federation

    Site Not Available

  • Moscow,
    Russian Federation

    Site Not Available

  • Saint Petersburg,
    Russian Federation

    Site Not Available

  • Samara,
    Russian Federation

    Site Not Available

  • Hospitalet de Llobregat, Barcelona
    Spain

    Site Not Available

  • Caceres, Cáceres
    Spain

    Site Not Available

  • Barcelona,
    Spain

    Site Not Available

  • Girona,
    Spain

    Site Not Available

  • Madrid,
    Spain

    Site Not Available

  • Valencia,
    Spain

    Site Not Available

  • Zaragoza,
    Spain

    Site Not Available

  • empty

    Bangkoknoi, Bangkok 10700
    Thailand

    Site Not Available

  • empty

    Ratchathewi, Bangkok 10400
    Thailand

    Site Not Available

  • empty

    Muang, Chiang Mai 50200
    Thailand

    Site Not Available

  • empty

    Klong Luang, Pathumthani 12120
    Thailand

    Site Not Available

  • New Cross Hospital

    Wolverhampton, West Midlands WV10 0QP
    United Kingdom

    Site Not Available

  • empty

    Leeds, West Yorkshire
    United Kingdom

    Site Not Available

  • Birmingham, Alabama
    United States

    Site Not Available

  • Phoenix, Arizona
    United States

    Site Not Available

  • Little Rock, Arkansas
    United States

    Site Not Available

  • Coronado, California
    United States

    Site Not Available

  • Loma Linda, California
    United States

    Site Not Available

  • empty

    Aurora, Colorado
    United States

    Site Not Available

  • Denver, Colorado
    United States

    Site Not Available

  • empty

    New Haven, Connecticut
    United States

    Site Not Available

  • Miami, Florida
    United States

    Site Not Available

  • Maywood, Illinois
    United States

    Site Not Available

  • Indianapolis, Indiana
    United States

    Site Not Available

  • New Orleans, Louisiana
    United States

    Site Not Available

  • Baltimore, Maryland
    United States

    Site Not Available

  • Boston, Massachusetts
    United States

    Site Not Available

  • Detroit, Michigan
    United States

    Site Not Available

  • Kansas City, Missouri
    United States

    Site Not Available

  • New York, New York
    United States

    Site Not Available

  • Statesville, North Carolina
    United States

    Site Not Available

  • Charleston, South Carolina
    United States

    Site Not Available

  • empty

    Dallas, Texas
    United States

    Site Not Available

  • Houston, Texas
    United States

    Site Not Available

  • San Antonio, Texas
    United States

    Site Not Available

  • Charlottesville, Virginia
    United States

    Site Not Available

  • Richmond, Virginia
    United States

    Site Not Available

  • Seattle, Washington
    United States

    Site Not Available

Map preview placeholder

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.