Eltrombopag To Reduce The Need For Platelet Transfusion In Subjects With Chronic Liver Disease And Thrombocytopenia Undergoing Elective Invasive Procedures
Condition: Non-alcoholic Steatohepatitis; Chronic Liver Disease; HCV; NASH - Nonalcoholic Steatohepatitis; HIV Infection; Thrombocytopenia; Hepatitis C Virus; HBV; Human Immunodeficiency Virus; Liver Diseases; Hepatitis B Virus
MeSH terms: Hepatitis A; Hepatitis C; HIV Infections; Hepatitis B; Acquired Immunodeficiency Syndrome; Hepatitis; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Thrombocytopenia
Intervention: Eltrombopag; Placebo
Intervention description: 75 mg, once daily, oral; placebo, once daily, oral
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 292.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: elective invasive procedure.; platelet transfusion; chronic liver disease-related thrombocytopenia; platelets; thrombopoietin

Summary:

      The purpose of this study is to assess the ability of eltrombopag to elevate platelet counts
      thereby reducing the need for platelet transfusions in chronic liver disease patients with
      thrombocytopenia undergoing elective invasive procedures. The clinical benefit of eltrombopag
      will be measured by the proportion of subjects who avoid platelet transfusions, before,
      during and up to 7 days after undergoing an invasive procedure. In addition, bleeding events
      will be monitored during this time. The number of transfusions, safety events and medical
      resource utilisation will be monitored during this time and for up to 30 days after
      undergoing an invasive procedure to help further evaluate clinical benefit.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female subjects, 18 years of age or more with chronic liver disease.

          -  Child-Pugh score of 12 or less.

          -  Model of End Stage Liver Disease (MELD) score of 24 or less.

          -  Subjects who, in the opinion of the investigator, are appropriate candidates to
             undergo an elective invasive procedure and who require a platelet transfusion to
             manage the risk of bleeding associated with the procedure.

          -  A baseline platelet count <50,000/µL.

          -  A baseline serum sodium level >130mEq/L.

          -  Haemoglobin concentration >8g/dL stable for at least one month.

          -  A female is eligible to enter and participate in the study if she is of:

        Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including
        any female who:

          -  Has had a hysterectomy

          -  Has had a bilateral oophorectomy (ovariectomy)

          -  Has had a bilateral tubal ligation

          -  Is post-menopausal (demonstrate total cessation of menses for greater than one year)

        Childbearing potential, has a negative urine and/or serum pregnancy test at screening, and
        within the 24 hour period prior to the first dose of investigational product and uses one
        of the following acceptable methods of contraception:

          -  Complete abstinence from intercourse for two weeks before exposure to the study drug,
             throughout the clinical study, and for 28 days after completion or premature
             discontinuation from the study to account for the elimination of the study drug
             (minimum of 5 half-lives).

          -  Any intrauterine device (IUD) with a documented failure rate of less than 1% per year.

          -  Double-barrier contraception (condom with spermicidal jelly, or diaphragm with
             spermicide).

          -  Male partner who is sterile (diagnosed by a qualified medical professional) prior to
             the female subject's study entry and is the sole sexual partner for that female.

          -  Oral contraceptive (either combined or progesterone only).

          -  Any other contraceptive method with a documented failure rate of <1% per year.

          -  Subject has no physical limitation to ingest and retain oral medication.

          -  Subject is able to understand and comply with protocol requirements and instructions
             and is likely to complete the study as planned.

          -  Subject is able to provide signed and dated written informed consent.

          -  In France, a subject will be eligible for inclusion in this study only if either
             affiliated to or a beneficiary of a social security category.

        Exclusion Criteria:

          -  Subjects with a known hypersensitivity, intolerance or allergy to any of the
             ingredients in eltrombopag tablets.

          -  Evidence of portal vein thrombosis on abdominal imaging (ultrasound with Doppler or
             appropriate MRI/CT imaging techniques) within 3 months of study start.

          -  History of arterial or venous thrombosis, including Budd-Chiari Syndrome, AND ≥ two of
             the following risk factors: hereditary thrombophilic disorders (e.g. Factor V Leiden,
             ATIII deficiency, etc.), hormone replacement therapy, systemic contraception therapy
             (containing oestrogen), smoking, diabetes, hypercholesterolemia, medication for
             hypertension or cancer.

          -  Any disease condition associated with current active WHO Grade 3 or 4 bleeding.

          -  Active infection requiring systemic antibiotic therapy. Prophylactic use of
             antibiotics is permitted.

          -  Pregnant or nursing women.

          -  Treatment with an investigational drug within 30 days or five half-lives (whichever is
             longer) preceding the first dose of study medication.

          -  History of platelet agglutination abnormality that prevents reliable measurement of
             platelet counts.

          -  History of porphyria.

          -  Previous participation in TPL104054.