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Eltrombopag To Reduce The Need For Platelet Transfusion In Subjects With Chronic Liver Disease And Thrombocytopenia Undergoing Elective Invasive Procedures (ELEVATE)
This study has been suspended.
( IDMC Recommendation )
First Received: May 13, 2008   Last Updated: November 12, 2009   History of Changes
Sponsor: GlaxoSmithKline
Information provided by: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00678587
  Purpose

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.


Condition Intervention Phase
Thrombocytopenia
Chronic Liver Disease
Hepatitis C Virus
HCV
Hepatitis B Virus
HBV
Human Immunodeficiency Virus
HIV Infection
Non-alcoholic Steatohepatitis
NASH.
Drug: Placebo
Drug: Eltrombopag
Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study
Official Title: Randomised, Double-Blind, Placebo-Controlled, Multi-Centre Study to Evaluate the Safety and Efficacy of Eltrombopag to Reduce the Need for Platelet Transfusion in Thrombocytopenic Subjects With Chronic Liver Disease Undergoing Elective Invasive Procedures

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Proportion of subjects with chronic liver disease and thrombocytopenia who do not require a platelet transfusion prior to, during and up to seven days following elective invasive procedures. [ Time Frame: Prior to, during and up to seven days following elective invasive procedures ]

Secondary Outcome Measures:
  • Proportion of subjects with bleeding prior to, during and up to seven days following elective invasive procedures [ Time Frame: Prior to, during and up to seven days following elective invasive procedures ]
  • Assessment of safety and tolerability of eltrombopag compared with placebo, as measured by the nature and frequency of adverse events, laboratory abnormalities, ocular examinations, 12 lead electrocardiograms (ECG), and clinical monitoring/observation. [ Time Frame: Throughout the study ]
  • Number of platelet transfusions administered prior to, during and up to 4 weeks (30 days) following elective invasive procedures in subjects receiving eltrombopag compared to placebo. [ Time Frame: Prior to, during and up to 4 weeks (30 days) following elective invasive procedures ]
  • (iii) non transfusion, non bleeding/transfusion complications, or scheduled surgical follow-up visits or scheduled blood-work, prior to, during and up to 4 weeks (30 days) following elective invasive procedures across treatment arms. [ Time Frame: Prior to, during and up to 4 weeks (30 days) following elective invasive procedures ]
  • Assessment of platelet counts throughout the study. [ Time Frame: Throughout the study ]
  • Population PK parameters of eltrombopag including AUC, clearance (CL/F), absorption rate constant (ka), and volume of distribution (V/F), with an assessment of potential significant covariates influencing eltrombopag pharmacokinetics. [ Time Frame: Throughout the study ]
  • Investigation of the relationship between eltrombopag PK and platelet response and relevant safety and efficacy endpoints. [ Time Frame: Throughout the study ]
  • Medical resource utilisation associated with (i) the management of complications of platelet or other blood product transfusions [ Time Frame: Prior to, during and up to 4 weeks (30 days) following elective invasive procedures ]
  • (ii) the management of complications of haemorrhagic events and [ Time Frame: Prior to, during and up to 4 weeks (30 days) following elective invasive procedures ]

Estimated Enrollment: 500
Study Start Date: June 2008
Estimated Study Completion Date: August 2010
Estimated Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active: Active Comparator
75 mg, once daily, oral
Drug: Eltrombopag
75 mg, once daily, oral
Placebo: Placebo Comparator
placebo, once daily, oral
Drug: Placebo
placebo, once daily, oral

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00678587

  Show 114 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GSK ( Study Director )
Study ID Numbers: TPL104054
Study First Received: May 13, 2008
Last Updated: November 12, 2009
ClinicalTrials.gov Identifier: NCT00678587     History of Changes
Health Authority: European Union: European Medicines Agency;   United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
thrombopoietin
chronic liver disease-related thrombocytopenia
platelets
platelet transfusion
elective invasive procedure.

Additional relevant MeSH terms:
Liver Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Flaviviridae Infections
Hepatitis, Viral, Human
Fatty Liver
Infection
Hepadnaviridae Infections
Thrombocytopenia
Hepatitis B
Hepatitis C
Retroviridae Infections
RNA Virus Infections
Immune System Diseases
Hematologic Diseases
Blood Platelet Disorders
Acquired Immunodeficiency Syndrome
Immunologic Deficiency Syndromes
Virus Diseases
Hepatitis
Digestive System Diseases
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections
DNA Virus Infections

ClinicalTrials.gov processed this record on November 20, 2009