Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01976104




Registration number
NCT01976104
Ethics application status
Date submitted
24/10/2013
Date registered
5/11/2013
Date last updated
27/02/2018

Titles & IDs
Public title
Treatment of Thrombocytopenia in Patients With Chronic Liver Disease Undergoing an Elective Procedure
Scientific title
A Randomized, Global, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Once-daily Oral Avatrombopag for the Treatment of Adults With Thrombocytopenia Associated With Liver Disease Prior to an Elective Procedure
Secondary ID [1] 0 0
2013-000934-36
Secondary ID [2] 0 0
E5501-G000-311
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Thrombocytopenia Associated With Liver Disease 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 0 0 0 0
Liver
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - avatrombopag (lower baseline platelet count)
Treatment: Drugs - placebo (lower baseline platelet count)
Treatment: Drugs - avatrombopag (higher baseline platelet count)
Treatment: Drugs - placebo (higher baseline platelet count)

Experimental: Group A (avatrombopag, lower baseline platelet count) - 60 mg avatrombopag (3 x 20 mg tablets) once daily on Days 1 through 5

Placebo Comparator: Group B (placebo, lower baseline platelet count) - placebo (3 x 20 mg matching placebo tablets) once daily on Days 1 through 5

Experimental: Group C (avatrombopag, higher baseline platelet count) - 40 mg avatrombopag (2 x 20 mg tablets) once daily on Days 1 through 5

Placebo Comparator: Group D (placebo, higher baseline platelet count) - placebo (2 x 20 mg matching placebo tablets) once daily on Days 1 through 5


Treatment: Drugs: avatrombopag (lower baseline platelet count)
60 mg avatrombopag (3 x 20 mg tablets)

Treatment: Drugs: placebo (lower baseline platelet count)
60 mg placebo (3 x 20 mg matching placebo tablets)

Treatment: Drugs: avatrombopag (higher baseline platelet count)
40 mg avatrombopag (2 x 20 mg tablets)

Treatment: Drugs: placebo (higher baseline platelet count)
40 mg placebo (2 x 20 mg matching placebo tablets)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Who Did Not Require a Platelet Transfusion After Randomization and up to 7 Days Following a Scheduled Procedure
Timepoint [1] 0 0
Randomization (Visit 2), up to 7 Days following a scheduled procedure
Secondary outcome [1] 0 0
Percentage of Participants Who Achieved a Platelet Count Greater Than or Equal to 50 x 10^9/L on Scheduled Procedure Day
Timepoint [1] 0 0
Day 10 to Day 13 (Visit 4)
Secondary outcome [2] 0 0
Change From Baseline in Platelet Counts on Scheduled Procedure Day
Timepoint [2] 0 0
Baseline (Visit 2) to Procedure Day 10 to Day 13 (Visit 4)

Eligibility
Key inclusion criteria
Inclusion Criteria

1. Participants greater than or equal to 18 years of age at Screening with chronic liver
disease

2. Participants who have a mean baseline platelet count of less than 50 x 10^9/L.
Platelet counts must be measured on 2 separate occasions, during the Screening Period
and at Baseline, and must be performed at least one day apart with neither platelet
count greater than 60 x 10^9/L. The mean of these 2 platelet counts (mean baseline
platelet count) will be used for entry criteria and for assignment to the low or high
baseline platelet count cohort.

3. Participants scheduled to undergo a permitted elective procedure who, in the opinion
of the investigator, will require a platelet transfusion to address a risk of bleeding
associated with the procedure unless there is a clinically significant increase in
platelet count from baseline

4. Model For End-stage Liver Disease (MELD) score less than or equal to 24 at Screening

5. If taking inhibitors of P glycoprotein (P-gp), except for verapamil, dose must be
stable for 7 days prior to Screening

6. Provide written informed consent

7. Willing and able to comply with all aspects of the protocol
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

1. Any history of arterial or venous thrombosis, including partial or complete thrombosis

2. Evidence of thrombosis (partial or complete) in the main portal vein, portal vein
branches, or any part of the splenic mesenteric system at Screening

3. Portal vein blood flow velocity rate <10 centimeters/second at Screening

4. Hepatic encephalopathy that cannot be effectively treated

5. Participants with HCC with Barcelona Clinic Liver Cancer (BCLC) staging classification
C or D

6. Platelet transfusion or receipt of blood products containing platelets within 7 days
of Screening. However packed red blood cells are permitted.

7. Heparin, warfarin, nonsteroidal anti-inflammatory drugs (NSAID), aspirin, verapamil,
and antiplatelet therapy with ticlopidine or glycoprotein IIb/IIIa antagonists (eg,
tirofiban) within 7 days of Screening

8. Use of erythropoietin stimulating agents within 7 days of Screening

9. Interferon (IFN) use within 14 days of Screening

10. Estrogen-containing hormonal contraceptive or hormone replacement therapy use within
30 days of Screening

11. Active infection requiring systemic antibiotic therapy within 7 days of Screening.
However, prophylactic use of antibiotics is permitted.

12. Alcohol abuse, alcohol dependence syndrome, drug abuse, or drug dependence within 6
months of the study start (unless participating in a controlled rehabilitation
program) or acute alcoholic hepatitis (chronic alcoholic hepatitis is allowed) within
6 months of the study start

13. Elective procedure performed prior to Visit 4 (Procedure Day)

14. Known to be human immunodeficiency virus positive

15. Any clinically significant acute or active bleeding (eg, gastrointestinal, central
nervous system)

16. Known history of any primary hematologic disorder (eg, immune thrombocytopenic
purpura, myelodysplastic syndrome)

17. Known medical history of genetic prothrombotic syndromes (eg, Factor V Leiden;
prothrombin G20210A; ATIII deficiency, etc.)

18. Participants with a history of significant cardiovascular disease (eg, congestive
heart failure New York Heart Association Grade III/IV, arrhythmia known to increase
the risk of thromboembolic events [eg, atrial fibrillation], coronary artery stent
placement, angioplasty, and coronary artery bypass grafting)

19. Females of childbearing potential who have had unprotected sexual intercourse within
30 days before study entry and who do not agree to use a highly effective method of
contraception (eg, total abstinence, an intrauterine device, a double-barrier method
[such as condom plus diaphragm with spermicide], a progesterone-only contraceptive
implant/injection, or have a vasectomized partner with confirmed azoospermia)
throughout the entire study period and for 30 days after study drug discontinuation.
If currently abstinent, the participant must agree to use a double-barrier method as
described above if she becomes sexually active during the study period or for 30 days
after study drug discontinuation. All females will be considered to be of childbearing
potential unless they are postmenopausal (at least 12 months consecutive amenorrhea in
the appropriate age group and without other known or suspected cause) or have been
sterilized surgically (ie, bilateral tubal ligation, hysterectomy, or bilateral
oophorectomy) at least 1 month before dosing.

20. Females who are lactating or pregnant at Screening or Baseline (as documented by a
positive serum beta-human chorionic gonadotropin [B-hCG] test with a minimum
sensitivity 25 IU/L or equivalent units of B-hCG). A separate baseline assessment is
required if a negative screening pregnancy test was obtained more than 72 hours before
the first dose of study drug.

21. Post liver transplant subjects

22. Any participant who has previously received avatrombopag

23. Hypersensitivity to avatrombopag maleate or any of its excipients

24. Hemoglobin levels = 8.0 or = 18.0 g/dL for men and > 15 for women at Screening, with
hematocrit = 54% for men and = 45% for women

25. Current malignancy including solid tumors and hematologic malignancies (except HCC)

26. Any history of concomitant medical condition that, in the opinion of the
investigator(s), would compromise the participant's ability to safely complete the
study

27. Currently enrolled in another clinical trial with any investigational drug or device
within 30 days of Screening

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
21/02/2017
Sample size
Target
Accrual to date
Final
204
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
- Clayton
Recruitment hospital [2] 0 0
- Footscray
Recruitment hospital [3] 0 0
- Melbourne
Recruitment hospital [4] 0 0
- Parkville
Recruitment postcode(s) [1] 0 0
- Clayton
Recruitment postcode(s) [2] 0 0
- Footscray
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment postcode(s) [4] 0 0
- Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Kansas
Country [10] 0 0
United States of America
State/province [10] 0 0
Louisiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Maryland
Country [12] 0 0
United States of America
State/province [12] 0 0
Massachusetts
Country [13] 0 0
United States of America
State/province [13] 0 0
Michigan
Country [14] 0 0
United States of America
State/province [14] 0 0
Missouri
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
South Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Virginia
Country [20] 0 0
United States of America
State/province [20] 0 0
Washington
Country [21] 0 0
Argentina
State/province [21] 0 0
Ciudad Autonoma Buenos Aires
Country [22] 0 0
Argentina
State/province [22] 0 0
Cordoba
Country [23] 0 0
Argentina
State/province [23] 0 0
Rosario
Country [24] 0 0
Belgium
State/province [24] 0 0
Edegem
Country [25] 0 0
Belgium
State/province [25] 0 0
Gent
Country [26] 0 0
Belgium
State/province [26] 0 0
Liege
Country [27] 0 0
Brazil
State/province [27] 0 0
Aracaju
Country [28] 0 0
Brazil
State/province [28] 0 0
Botucatu
Country [29] 0 0
Brazil
State/province [29] 0 0
Porto Alegre
Country [30] 0 0
Brazil
State/province [30] 0 0
Salvador
Country [31] 0 0
Canada
State/province [31] 0 0
Calgary
Country [32] 0 0
Canada
State/province [32] 0 0
Edmonton
Country [33] 0 0
China
State/province [33] 0 0
Anhui
Country [34] 0 0
China
State/province [34] 0 0
Beijing
Country [35] 0 0
China
State/province [35] 0 0
Hebei
Country [36] 0 0
China
State/province [36] 0 0
Jiangsu
Country [37] 0 0
China
State/province [37] 0 0
Shaanxi
Country [38] 0 0
China
State/province [38] 0 0
Shanxi
Country [39] 0 0
China
State/province [39] 0 0
Sichuan
Country [40] 0 0
China
State/province [40] 0 0
Zheijiang
Country [41] 0 0
Czechia
State/province [41] 0 0
Brno
Country [42] 0 0
Czechia
State/province [42] 0 0
Havirov
Country [43] 0 0
Czechia
State/province [43] 0 0
Ostrava
Country [44] 0 0
Czechia
State/province [44] 0 0
Praha 2
Country [45] 0 0
Czechia
State/province [45] 0 0
Praha 4
Country [46] 0 0
Czechia
State/province [46] 0 0
Usti nad Labem
Country [47] 0 0
France
State/province [47] 0 0
Alpes Maritimes
Country [48] 0 0
France
State/province [48] 0 0
Hauts De Seine
Country [49] 0 0
France
State/province [49] 0 0
Ille Et Vilaine
Country [50] 0 0
France
State/province [50] 0 0
Rhone
Country [51] 0 0
France
State/province [51] 0 0
Val De Marne
Country [52] 0 0
Germany
State/province [52] 0 0
Baden Wuerttemberg
Country [53] 0 0
Germany
State/province [53] 0 0
Hessen
Country [54] 0 0
Germany
State/province [54] 0 0
Niedersachsen
Country [55] 0 0
Germany
State/province [55] 0 0
Nordrhein Westfalen
Country [56] 0 0
Germany
State/province [56] 0 0
Sachsen
Country [57] 0 0
Germany
State/province [57] 0 0
Schleswig Holstein
Country [58] 0 0
Germany
State/province [58] 0 0
Hamburg
Country [59] 0 0
Israel
State/province [59] 0 0
Haifa
Country [60] 0 0
Israel
State/province [60] 0 0
Holon
Country [61] 0 0
Israel
State/province [61] 0 0
Jerusalem
Country [62] 0 0
Israel
State/province [62] 0 0
Nahariya
Country [63] 0 0
Israel
State/province [63] 0 0
Petach Tikva
Country [64] 0 0
Israel
State/province [64] 0 0
Ramat-Gan
Country [65] 0 0
Israel
State/province [65] 0 0
Rechovot
Country [66] 0 0
Israel
State/province [66] 0 0
Tel Aviv
Country [67] 0 0
Italy
State/province [67] 0 0
Modena
Country [68] 0 0
Italy
State/province [68] 0 0
Firenze
Country [69] 0 0
Italy
State/province [69] 0 0
Milano
Country [70] 0 0
Italy
State/province [70] 0 0
Pisa
Country [71] 0 0
Italy
State/province [71] 0 0
Roma
Country [72] 0 0
Italy
State/province [72] 0 0
Trento
Country [73] 0 0
Japan
State/province [73] 0 0
Hokkaido
Country [74] 0 0
Japan
State/province [74] 0 0
Hyogo
Country [75] 0 0
Japan
State/province [75] 0 0
Iwate
Country [76] 0 0
Japan
State/province [76] 0 0
Kagawa
Country [77] 0 0
Japan
State/province [77] 0 0
Oita
Country [78] 0 0
Japan
State/province [78] 0 0
Okayama
Country [79] 0 0
Japan
State/province [79] 0 0
Osaka
Country [80] 0 0
Japan
State/province [80] 0 0
Saitama
Country [81] 0 0
Japan
State/province [81] 0 0
Tokyo
Country [82] 0 0
Japan
State/province [82] 0 0
Chiba
Country [83] 0 0
Japan
State/province [83] 0 0
Niigata
Country [84] 0 0
Japan
State/province [84] 0 0
Tokushima
Country [85] 0 0
Japan
State/province [85] 0 0
Wakayama
Country [86] 0 0
Mexico
State/province [86] 0 0
Jalisco
Country [87] 0 0
Mexico
State/province [87] 0 0
Nuevo León
Country [88] 0 0
Mexico
State/province [88] 0 0
Veracruz
Country [89] 0 0
Mexico
State/province [89] 0 0
Yucatán
Country [90] 0 0
Mexico
State/province [90] 0 0
Durango
Country [91] 0 0
Romania
State/province [91] 0 0
Arad
Country [92] 0 0
Romania
State/province [92] 0 0
Bucharest
Country [93] 0 0
Romania
State/province [93] 0 0
Bucuresti
Country [94] 0 0
Romania
State/province [94] 0 0
Craiova
Country [95] 0 0
Romania
State/province [95] 0 0
Iasi
Country [96] 0 0
Romania
State/province [96] 0 0
Sibiu
Country [97] 0 0
Romania
State/province [97] 0 0
Timisoara
Country [98] 0 0
Russian Federation
State/province [98] 0 0
Kemerovo
Country [99] 0 0
Russian Federation
State/province [99] 0 0
Moscow
Country [100] 0 0
Russian Federation
State/province [100] 0 0
Saint Petersburg
Country [101] 0 0
Russian Federation
State/province [101] 0 0
Samara
Country [102] 0 0
Spain
State/province [102] 0 0
Barcelona
Country [103] 0 0
Spain
State/province [103] 0 0
Cáceres
Country [104] 0 0
Spain
State/province [104] 0 0
Girona
Country [105] 0 0
Spain
State/province [105] 0 0
Madrid
Country [106] 0 0
Spain
State/province [106] 0 0
Valencia
Country [107] 0 0
Spain
State/province [107] 0 0
Zaragoza

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eisai Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a global, multicenter, randomized, double-blind, placebo-controlled, parallel group
study using avatrombopag to treat adults with thrombocytopenia associated with liver disease.
The study will evaluate avatrombopag in the treatment of thrombocytopenia associated with
liver disease prior to an elective procedure to reduce the need for platelet transfusions or
any rescue procedure for bleeding due to procedural and post-procedural bleeding
complications. Participants will be enrolled into 2 cohorts according to mean baseline
platelet count and, within each baseline platelet count cohort will be further stratified by
risk of bleeding associated with the elective procedure (low, moderate, or high) and
hepatocellular carcinoma (HCC) status (Yes or No).
Trial website
https://clinicaltrials.gov/ct2/show/NCT01976104
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01976104