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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01972529




Registration number
NCT01972529
Ethics application status
Date submitted
24/10/2013
Date registered
30/10/2013
Date last updated
27/02/2018

Titles & IDs
Public title
Treatment of Thrombocytopenia in Patients With Chronic Liver DiseaseUndergoing 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
2013-000965-34
Secondary ID [2] 0 0
E5501-G000-310
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 or Any Rescue Procedure for Bleeding After Randomization Following a Scheduled Procedure
Timepoint [1] 0 0
Baseline (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 the Scheduled Procedure Day
Timepoint [1] 0 0
Day 10 to Day 13 (Visit 4)
Secondary outcome [2] 0 0
Change From Baseline in Platelet Count on the 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 participants

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
1/02/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/02/2017
Sample size
Target
Accrual to date
Final
231
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 0 0
- Camperdown
Recruitment hospital [2] 0 0
- Adelaide
Recruitment hospital [3] 0 0
- Bedford Park
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment postcode(s) [2] 0 0
- Adelaide
Recruitment postcode(s) [3] 0 0
- Bedford Park
Recruitment outside Australia
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United States of America
State/province [1] 0 0
California
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United States of America
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Florida
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United States of America
State/province [3] 0 0
Louisiana
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United States of America
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Michigan
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United States of America
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Minnesota
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United States of America
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Mississippi
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United States of America
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New York
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United States of America
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Pennsylvania
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United States of America
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Texas
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Argentina
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Buenos Aires
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Argentina
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Ciudad Autonoma Buenos Aires
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Argentina
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Mendoza
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Austria
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Linz
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Austria
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Vienna
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Austria
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Wien
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Belgium
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Bruxelles
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Belgium
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Leuven
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Brazil
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Rio Grande Do Sul
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Brazil
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Sao Paulo
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Canada
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Ontario
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Chile
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La Serena
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Chile
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Santiago
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China
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Hunan
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China
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Jiangsu
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China
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Shanghai
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China
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Beijing
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France
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Bas Rhin
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France
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Isere
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France
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Marne
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France
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Puy De Dome
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France
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Somme
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France
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Vandoeuvre les Nancy
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Germany
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Baden Wuerttemberg
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Germany
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Nordrhein Westfalen
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Germany
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Schleswig Holstein
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Germany
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Hamburg
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Hungary
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Bekescsaba
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Hungary
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Budapest
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Hungary
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Dunaujvaros
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Gyula
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Kaposvar
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Kecskemet
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Szombathely
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Zalaegerszeg
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Italy
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Foggia
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Bari
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Bologna
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Genova
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Milano
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Modena
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Palermo
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Udine
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Korea, Republic of
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Gangwon-do
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Korea, Republic of
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Gyeonggi-do
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Gyeongnam
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Korea, Republic of
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Jeollanam-do
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Korea, Republic of
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Busan
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Korea, Republic of
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Daegu
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Korea, Republic of
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Incheon
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Korea, Republic of
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Seoul
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Poland
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Katowice
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Lodz
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Myslowice
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Szczecin
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Coimbra
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Lisboa
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Porto
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Vila Real
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Viseu
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Barcelona
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Sevilla
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Valencia
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Valladolid
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Taiwan
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Kaohsiung
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Taichung
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Tainan
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Taipei
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Taiwan
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Taoyuan City
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Thailand
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Bangkok
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Thailand
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Chiang Mai
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Thailand
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Pathumthani
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United Kingdom
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Cornwall
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United Kingdom
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Greater London
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United Kingdom
State/province [87] 0 0
Greater Manchester
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United Kingdom
State/province [88] 0 0
West Midlands
Country [89] 0 0
United Kingdom
State/province [89] 0 0
West Yorkshire

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/NCT01972529
Trial related presentations / publications
Public notes

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