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

History of Changes

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
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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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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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.

[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 ]

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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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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 ]

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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 ]

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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 ]

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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 ]

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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 ]

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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) ]

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9. Secondary:

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

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10. Secondary:

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

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11. Secondary:

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

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12. Secondary:

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

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13. Secondary:

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

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14. Secondary:

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

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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 ]

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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 ]

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Serious Adverse Events

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Other Adverse Events

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Limitations and Caveats

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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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:

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.

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

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