Clinical trial NCT00678587: Eltrombopag To Reduce The Need For Platelet Transfusion In Subjects With Chronic Liver Disease And Thrombocytopenia Undergoing Elective Invasive Procedures
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: 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
Keywords: elective invasive procedure.
platelet transfusion
chronic liver disease-related thrombocytopenia
platelets
thrombopoietin
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-05-15
Enrollment: 292
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Number of Participants With Chronic Liver Disease and Thrombocytopenia (Platelets <50 Gi/L) Who do Not Require a Platelet Transfusion Prior to, During, and up to 7 Days Following Elective Invasive Procedures
timeFrame: Prior to, during, and up to seven days following elective invasive procedures (Study Days 16-19); therefore, this covers a time period from Baseline to Day 26
Secondary outcomes:
measure: Number of Participants With a World Health Organization (WHO) Bleeding Score >=2 During and up to 7 Days Following Elective Invasive Procedures
timeFrame: Prior to, during, and up to 7 days following elective invasive procedures (Study Days 16-19); therefore, this covers a time period from Baseline to Day 26
measure: Number of Participants With the Indicated Number of Platelet Transfusions Administered
timeFrame: Prior to, during, and up to 4 weeks (30 days) following elective invasive procedures (Days 16-19); therefore, this covers a time period from Baseline to Day 26
measure: Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline
timeFrame: Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 day follow-up; early withdrawal; and maximum post-baseline
measure: Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline
timeFrame: Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 day follow-up; and maximum post-baseline
measure: Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category
timeFrame: Screening to Procedure +30 day follow-up or early withdrawal
measure: Number of Participants With a Serious Adverse Event That Occurred in Greater Than One Participant
timeFrame: Screening to Procedure +30 day follow-up or early withdrawal
measure: Number of Participants With the Indicated Event Relating to Vision
timeFrame: Screening or Baseline and at End of Study (Procedure +30 day follow-up or withdrawal visit)
measure: Number of Participants With Renal Function Abnormality
timeFrame: Screening to Procedure +30 day follow-up or early withdrawal
measure: Number of Participants With a Clinically Significant Change in Electrocardiogram (ECG) Results
timeFrame: Screening, Baseline, Day 15, and Withdrawal
measure: Pharmacokinetics (PK) of Eltrombopag, Steady State AUC(0-tau)
timeFrame: Day 14
measure: Pharmacokinetics (PK) of Eltrombopag, Cmax
timeFrame: Day 14
measure: Pharmacokinetics (PK) of Eltrombopag, t1/2
timeFrame: Day 14
measure: Pharmacokinetics (PK) of Eltrombopag, CL/F
timeFrame: Day 14
measure: Mean Number of Days Spent in the Hospital
timeFrame: Prior to, during, and up to 4 weeks (30 days) following elective invasive procedures (Days 16-19); therefore, this covers a time period from Baseline to Day 26
measure: Mean Number of Unscheduled Office Visits, Unscheduled Laboratory Tests, and Unscheduled Procedures
timeFrame: Prior to, during, and up to 4 weeks (30 days) following elective invasive procedures (Days 16-19); therefore, this covers a time period from Baseline to Day 26
Other outcomes:
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city: Lahore
country: Pakistan
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city: Saint-Petersburg
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city: Smolensk
country: Russian Federation
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city: Barakaldo
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city: Barcelona
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city: Barcelona
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city: Barcelona
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Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Afdhal NH, Giannini EG, Tayyab G, Mohsin A, Lee JW, Andriulli A, Jeffers L, McHutchison J, Chen PJ, Han KH, Campbell F, Hyde D, Brainsky A, Theodore D; ELEVATE Study Group. Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia. N Engl J Med. 2012 Aug 23;367(8):716-24. doi: 10.1056/NEJMoa1110709.