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 terminated.
(GSK decision)
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00678587
First received: May 13, 2008
Last updated: February 7, 2013
Last verified: January 2013
Results First Received: October 10, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Non-alcoholic Steatohepatitis
Chronic Liver Disease
HCV
NASH.
HIV Infection
Thrombocytopenia
Hepatitis C Virus
HBV
Human Immunodeficiency Virus
Liver Diseases
Hepatitis B Virus
Interventions: Drug: Eltrombopag
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Placebo Matching placebo
Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily

Participant Flow:   Overall Study
    Placebo     Eltrombopag 75 mg  
STARTED     147     145  
COMPLETED     127     127  
NOT COMPLETED     20     18  
Adverse Event                 3                 3  
Lack of Efficacy                 1                 0  
Protocol Violation                 2                 1  
Study Closed/Terminated                 1                 0  
Lost to Follow-up                 3                 5  
Investigator Discretion                 2                 6  
Withdrew Consent                 8                 3  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
Placebo Matching placebo
Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily
Total Total of all reporting groups

Baseline Measures
    Placebo     Eltrombopag 75 mg     Total  
Number of Participants  
[units: participants]
  147     145     292  
Age  
[units: Years]
Mean ± Standard Deviation
  53.5  ± 11.78     51.6  ± 11.04     52.5  ± 11.44  
Gender  
[units: Participants]
     
Female     55     49     104  
Male     92     96     188  
Race/Ethnicity, Customized  
[units: participants]
     
White     93     85     178  
Central/South Asian Heritage     33     41     74  
Japanese/East Asian/South East Asian Heritage     19     14     33  
African American/African Heritage     2     4     6  
Native Hawaiian/Other Pacific Islander and White     0     1     1  
Number of participants categorized into the indicated Child-Pugh (CP) Class [1]
[units: participants]
     
Child-Pugh Class A     59     68     127  
Child-Pugh Class B     64     57     121  
Child-Pugh Class C     17     10     27  
Model for End-Stage Liver Disease (MELD) Score at Baseline [2]
[units: scores on a scale]
Median ( Full Range )
  12  
  ( 6 to 25 )  
  12  
  ( 6 to 24 )  
  12  
  ( 6 to 25 )  
[1] The CP score (ranging from 5 to 15; 5=mild, 15=severe), calculated based on total bilirubin, serum albumin, international normalized ratio, ascites, and hepatic encephalopathy, is used to assess liver disease severity. A CP score of 5 or 6 is classified as Class A (mild), a score of 7-9 is classified as Class B (moderate), and a score >=10 is classified as Class C (severe). Participants with a CP score <10 were enrolled in the study. The number of participants analyzed is 140 for placebo and 135 for Eltrombopag; not all participants were compliant and had their baseline CP score measured.
[2] MELD uses the following formula to calculate a participant’s likelihood of dying within 3 months from liver disease: 3.8 x log (e) (bilirubin milligrams [mg]/deciliter [dL]) + 11.2 x log (e) (international ratio for prothrombin time) + 9.6 log (e) (creatinine mg/dL). Scores range from 6 (least ill) to 40 (most ill): 40 or more, 71.3% mortality; 30-39, 52.6% mortality; 20-29, 19.6% mortality; 10-19, 6.0% mortality; <9, 1.9% mortality. The number of participants analyzed is 140 for placebo and 135 for Eltrombopag; not all participants were compliant and had their baseline MELD score measured.



  Outcome Measures
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1.  Primary:   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   [ Time Frame: 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 ]

2.  Secondary:   Number of Participants With a World Health Organization (WHO) Bleeding Score >=2 During and up to 7 Days Following Elective Invasive Procedures   [ Time Frame: 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 ]
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Measure Type Secondary
Measure Title Number of Participants With a World Health Organization (WHO) Bleeding Score >=2 During and up to 7 Days Following Elective Invasive Procedures
Measure Description The WHO Bleeding Scale was used to assess bleeding during the study. The range of possible scores is 0 to 4. Grade 0 is no bleeding; Grade 1 is petechiae (small [1-2 millimeter] red or purple spot on the body, caused by a minor hemorrhage); Grade 2 is mild blood loss; Grade 3 is gross blood loss (requiring a transfusion; and Grade 4 is debilitating blood loss (retinal or cerebral associated with fatality).
Time Frame 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population

Reporting Groups
  Description
Placebo Matching placebo
Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily

Measured Values
    Placebo     Eltrombopag 75 mg  
Number of Participants Analyzed  
[units: participants]
  147     145  
Number of Participants With a World Health Organization (WHO) Bleeding Score >=2 During and up to 7 Days Following Elective Invasive Procedures  
[units: participants]
  34     25  


Statistical Analysis 1 for Number of Participants With a World Health Organization (WHO) Bleeding Score >=2 During and up to 7 Days Following Elective Invasive Procedures
Groups [1] All groups
Risk Difference (RD) [2] -5.9
95% Confidence Interval ( -15.1 to 3.3 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
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3.  Secondary:   Number of Participants With the Indicated Number of Platelet Transfusions Administered   [ Time Frame: 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 ]

4.  Secondary:   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   [ Time Frame: Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 day follow-up; early withdrawal; and maximum post-baseline ]

5.  Secondary:   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   [ Time Frame: Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 day follow-up; and maximum post-baseline ]

6.  Secondary:   Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category   [ Time Frame: Screening to Procedure +30 day follow-up or early withdrawal ]

7.  Secondary:   Number of Participants With a Serious Adverse Event That Occurred in Greater Than One Participant   [ Time Frame: Screening to Procedure +30 day follow-up or early withdrawal ]

8.  Secondary:   Number of Participants With the Indicated Event Relating to Vision   [ Time Frame: Screening or Baseline and at End of Study (Procedure +30 day follow-up or withdrawal visit) ]

9.  Secondary:   Number of Participants With Renal Function Abnormality   [ Time Frame: Screening to Procedure +30 day follow-up or early withdrawal ]

10.  Secondary:   Number of Participants With a Clinically Significant Change in Electrocardiogram (ECG) Results   [ Time Frame: Screening, Baseline, Day 15, and Withdrawal ]

11.  Secondary:   Pharmacokinetics (PK) of Eltrombopag, Steady State AUC(0-tau)   [ Time Frame: Day 14 ]

12.  Secondary:   Pharmacokinetics (PK) of Eltrombopag, Cmax   [ Time Frame: Day 14 ]

13.  Secondary:   Pharmacokinetics (PK) of Eltrombopag, t1/2   [ Time Frame: Day 14 ]

14.  Secondary:   Pharmacokinetics (PK) of Eltrombopag, CL/F   [ Time Frame: Day 14 ]

15.  Secondary:   Mean Number of Days Spent in the Hospital   [ Time Frame: 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 ]

16.  Secondary:   Mean Number of Unscheduled Office Visits, Unscheduled Laboratory Tests, and Unscheduled Procedures   [ Time Frame: 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 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


No publications provided by GlaxoSmithKline

Publications automatically indexed to this study:

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00678587     History of Changes
Other Study ID Numbers: TPL104054
Study First Received: May 13, 2008
Results First Received: October 10, 2010
Last Updated: February 7, 2013
Health Authority: European Union: European Medicines Agency
United States: Food and Drug Administration