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AzTrials

Thrombocytopenia Associated With Liver DiseasePhase 3NCT01972529

Treatment of Thrombocytopenia in Patients With Chronic Liver DiseaseUndergoing an Elective Procedure

A Phase 3 study testing avatrombopag (lower baseline platelet count) and avatrombopag (higher baseline platelet count) in people with Thrombocytopenia Associated With Liver Disease, run by Eisai Inc. at 109 sites in 20 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
avatrombopag (lower baseline platelet count) and avatrombopag (higher baseline platelet count)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
231 participants
Where
109 sitesin 20 countries
Study dates
Feb 2014to 27 Feb 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants greater than or equal to 18 years of age at Screening with chronic liver disease
  • 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.
  • 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
  • Model For End-stage Liver Disease (MELD) score less than or equal to 24 at Screening
  • If taking inhibitors of P glycoprotein (P-gp), except for verapamil, dose must be stable for 7 days prior to Screening
  • Provide written informed consent
  • Willing and able to comply with all aspects of the protocol

Who cannot join

  • Any history of arterial or venous thrombosis, including partial or complete thrombosis
  • Evidence of thrombosis (partial or complete) in the main portal vein, portal vein branches, or any part of the splenic mesenteric system at Screening
  • Portal vein blood flow velocity rate <10 centimeters/second at Screening
  • Hepatic encephalopathy that cannot be effectively treated
  • Participants with HCC with Barcelona Clinic Liver Cancer (BCLC) staging classification C or D
  • Platelet transfusion or receipt of blood products containing platelets within 7 days of Screening. However packed red blood cells are permitted.
Show all 27Show fewer
  • 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
  • Use of erythropoietin stimulating agents within 7 days of Screening
  • Interferon (IFN) use within 14 days of Screening
  • Estrogen-containing hormonal contraceptive or hormone replacement therapy use within 30 days of Screening
  • Active infection requiring systemic antibiotic therapy within 7 days of Screening. However, prophylactic use of antibiotics is permitted.
  • 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
  • Elective procedure performed prior to Visit 4 (Procedure Day)
  • Known to be human immunodeficiency virus positive
  • Any clinically significant acute or active bleeding (eg, gastrointestinal, central nervous system)
  • Known history of any primary hematologic disorder (eg, immune thrombocytopenic purpura, myelodysplastic syndrome)
  • Known medical history of genetic prothrombotic syndromes (eg, Factor V Leiden; prothrombin G20210A; ATIII deficiency, etc.)
  • 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)
  • 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.
  • 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.
  • Post liver transplant participants
  • Any participant who has previously received avatrombopag
  • Hypersensitivity to avatrombopag maleate or any of its excipients
  • 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
  • Current malignancy including solid tumors and hematologic malignancies (except HCC)
  • 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
  • Currently enrolled in another clinical trial with any investigational drug or device within 30 days of Screening

Trial locations and contacts

109 sites in 20 countries.

109 sites in 20 countries

United States21 sites

  • Study site

    Dallas, Texas

  • Study site

    Harlingen, Texas

  • Study site

    Houston, Texas

  • Study site

    Jackson, Mississippi

  • Study site

    Jacksonville, Florida

  • Study site

    Lancaster, California

  • Study site

    Long Beach, California

  • Study site

    Los Angeles, California

  • Study site

    Minneapolis, Minnesota

  • Study site

    New Orleans, Louisiana

  • Study site

    New York, New York

  • Study site

    Palmetto Bay, Florida

  • Study site

    Philadelphia, Pennsylvania

  • Study site

    Pittsburgh, Pennsylvania

  • Study site

    Rochester, Michigan

  • Study site

    Sacramento, California

  • Study site

    San Antonio, Texas

  • Study site

    San Bernardino, California

  • Study site

    San Francisco, California

  • Study site

    Tampa, Florida

  • Study site

    The Bronx, New York

Other trials in United States

South Korea10 sites

  • Study site

    Busan

  • Study site

    Chuncheon, Gangwon-do

  • Study site

    Daegu

  • Study site

    Guri-si, Gyeonggi-do

  • Study site

    Hwasun, Jeollanam-do

  • Study site

    Incheon

  • Study site

    Seongnam-si, Gyeonggi-do

  • Study site

    Seoul

  • Study site

    Suwon, Gyeonggi-do

  • Study site

    Yangsan, Gyeongsangnam-do

Other trials in South Korea

Hungary8 sites

  • Study site

    Békéscsaba

  • Study site

    Budapest

  • Study site

    Dunaújváros

  • Study site

    Gyula

  • Study site

    Kaposvár

  • Study site

    Kecskemét

  • Study site

    Szombathely

  • Study site

    Zalaegerszeg

Other trials in Hungary

Italy8 sites

  • Study site

    Bari

  • Study site

    Bologna

  • Study site

    Genova

  • Study site

    Milan

  • Study site

    Modena

  • Study site

    Palermo

  • Study site

    San Giovanni Rotondo, Foggia

  • Study site

    Udine

Other trials in Italy

France6 sites

  • Study site

    Amiens, Somme

  • Study site

    Clermont-Ferrand, Puy De Dome

  • Study site

    Grenoble, Isere

  • Study site

    Reims, Marne

  • Study site

    Strasbourg, Bas Rhin

  • Study site

    Vandœuvre-lès-Nancy

Other trials in France

Portugal6 sites

  • Study site

    Coimbra

  • Study site

    Lisbon

  • Study site

    Porto

  • Study site

    Viana do Castelo

  • Study site

    Vila Real

  • Study site

    Viseu

Other trials in Portugal

Germany5 sites

  • Study site

    Cologne, North Rhine-Westphalia

  • Study site

    Freiburg im Breisgau, Baden-Wurttemberg

  • Study site

    Hamburg

  • Study site

    Herne, North Rhine-Westphalia

  • Study site

    Kiel, Schleswig-Holstein

Other trials in Germany

Poland5 sites

  • Study site

    Katowice

  • Study site

    Lodz

  • Study site

    Mysłowice

  • Study site

    Szczecin

  • Study site

    Wroclaw

Other trials in Poland

Spain5 sites

  • Study site

    Barcelona

  • Study site

    Pontevedra

  • Study site

    Seville

  • Study site

    Valencia

  • Study site

    Valladolid

Other trials in Spain

Taiwan5 sites

  • Study site

    Kaohsiung City

  • Study site

    Taichung

  • Study site

    Tainan

  • Study site

    Taipei

  • Study site

    Taoyuan City

Other trials in Taiwan

United Kingdom5 sites

  • Study site

    Leeds, West Yorkshire

  • Study site

    London, Greater London

  • Study site

    Manchester, Greater Manchester

  • Study site

    Truro, Cornwall

  • Study site

    Wolverhampton, West Midlands

Other trials in United Kingdom

China4 sites

  • Study site

    Beijing

  • Study site

    Changsha, Hu'nan

  • Study site

    Nanjing, Jiangsu

  • Study site

    Shanghai, Shanghai Municipality

Other trials in China

Thailand4 sites

  • Study site

    Bangkoknoi, Bangkok

  • Study site

    Khlong Luang, Changwat Pathum Thani

  • Study site

    Mueang Nonthaburi, Chiang Mai

  • Study site

    Ratchathewi, Bangkok

Other trials in Thailand

Argentina3 sites

  • Study site

    Ciudad Autonoma Buenos Aires

  • Study site

    Mendoza

  • Study site

    Pilar, Buenos Aires

Other trials in Argentina

Australia3 sites

  • Study site

    Adelaide, South Australia

  • Study site

    Bedford Park, South Australia

  • Study site

    Camperdown, New South Wales

Other trials in Australia

Brazil3 sites

  • Study site

    Porto Alegre, Rio Grande do Sul

  • Study site

    São José do Rio Preto, São Paulo

  • Study site

    São Paulo

Other trials in Brazil

Austria2 sites

  • Study site

    Linz

  • Study site

    Vienna

Other trials in Austria

Belgium2 sites

  • Study site

    Brussels

  • Study site

    Leuven

Other trials in Belgium

Canada2 sites

  • Study site

    London, Ontario

  • Study site

    Toronto, Ontario

Other trials in Canada

Chile2 sites

  • Study site

    La Serena

  • Study site

    Santiago

Other trials in Chile

About this study

Official 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

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).

Read the detailed description

This study will consist of 3 phases: Prerandomization, Randomization, and a Follow-up Phase. The Prerandomization Phase includes one Screening Visit that will take place from Day -14 through Day -1; the Randomization Phase includes the Baseline Period, Treatment Period, and Procedure Day Period (5 to 8 days after last dose of study drug [Study Day 10 to 13]). The Follow-up Phase comprises 2 visits: 7 days post Procedure Day and 30 days after receiving the last dose of study drug. Permitted procedures include: Paracentesis; Thoracentesis; Gastrointestinal endoscopy with or without plans for biopsy, colonoscopy, polypectomy, or variceal banding; Liver biopsy; Bronchoscopy with or without plans for biopsy; Ethanol ablation therapy or chemoembolization for HCC; Vascular catheterization (including right side procedures in participants with pulmonary hypertension); Transjugular intrahepatic portosystemic shunt; Dental procedures; Renal biopsy; Biliary interventions; Nephrostomy tube placement; Radiofrequency ablation; and Laparoscopic interventions.

Being tested
avatrombopag (lower baseline platelet count), placebo (lower baseline platelet count), avatrombopag (higher baseline platelet count), placebo (higher baseline platelet count)
Keywords
Thrombocytopenia, Chronic Liver Disease
Medical subject headings
Thrombocytopenia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • avatrombopag (lower baseline platelet count)Drug

    60 mg avatrombopag (3 x 20 mg tablets)

  • placebo (lower baseline platelet count)Drug

    60 mg placebo (3 x 20 mg matching placebo tablets)

  • avatrombopag (higher baseline platelet count)Drug

    40 mg avatrombopag (2 x 20 mg tablets)

  • placebo (higher baseline platelet count)Drug

    40 mg placebo (2 x 20 mg matching placebo tablets)

Study groups in NCT01972529
Study groupRoleWhat they receive
Group A (avatrombopag, lower baseline platelet count)Experimental60 mg avatrombopag (3 x 20 mg tablets) once daily on Days 1 through 5
Receives: Drug: avatrombopag (lower baseline platelet count)
Group B (placebo, lower baseline platelet count)Placebo comparatorplacebo (3 x 20 mg matching placebo tablets) once daily on Days 1 through 5
Receives: Drug: placebo (lower baseline platelet count)
Group C (avatrombopag, higher baseline platelet count)Experimental40 mg avatrombopag (2 x 20 mg tablets) once daily on Days 1 through 5
Receives: Drug: avatrombopag (higher baseline platelet count)
Group D (placebo, higher baseline platelet count)Placebo comparatorplacebo (2 x 20 mg matching placebo tablets) once daily on Days 1 through 5
Receives: Drug: placebo (higher baseline platelet count)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants Who Did Not Require a Platelet Transfusion or Any Rescue Procedure for Bleeding After Randomization Following a Scheduled Procedure

    Responders were defined as participants who did not require a platelet transfusion or any rescue procedure for bleeding after randomization and up to 7 days following a scheduled procedure. Participants with missing information due to early withdrawal or other reasons were conservatively considered as having received a transfusion in the analysis, (i.e. a Non-responder).

    Measured: Baseline (Visit 2) up to 7 days following a scheduled procedure

Secondary outcomes (2)

  1. Percentage of Participants Who Achieved a Platelet Count Greater Than or Equal to 50 x 10^9/L on the Scheduled Procedure Day

    Responders were defined as participants who achieved a platelet count greater than or equal to 50 x 10^9/L on the procedure day. Participants with missing a platelet count on the procedure day were conservatively considered as not achieving a platelet count of 50x10^9/L in the analysis, (i.e. Non-responders).

    Measured: Day 10 to Day 13 (Visit 4)

  2. Change From Baseline in Platelet Count on the Scheduled Procedure Day

    Last observation carried forward was used for participants with a missing platelet count on the scheduled procedure day. Platelet count was measured preprocedure and before any platelet transfusion.

    Measured: Baseline (Visit 2) to Procedure Day 10 to Day 13 (Visit 4)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Oct 2013 (estimated)
  2. Study startFeb 2014
  3. Primary completion26 Jan 2017
  4. Study completion27 Feb 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
231 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01972529
Sponsor's protocol ID
E5501-G000-310
Other IDs
2013-000965-34
Status last verified
Jan 2018
First submitted
24 Oct 2013
Last updated
27 Feb 2018
Data monitoring committee
Yes

Publications

  • Poordad F, Terrault NA, Alkhouri N, Tian W, Allen LF, Rabinovitz M. Avatrombopag, an Alternate Treatment Option to Reduce Platelet Transfusions in Patients with Thrombocytopenia and Chronic Liver Disease-Integrated Analyses of 2 Phase 3 Studies. Int J Hepatol. 2020 Jan 25;2020:5421632. doi: 10.1155/2020/5421632. eCollection 2020.

    PubMed 32047671

  • Terrault N, Chen YC, Izumi N, Kayali Z, Mitrut P, Tak WY, Allen LF, Hassanein T. Avatrombopag Before Procedures Reduces Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia. Gastroenterology. 2018 Sep;155(3):705-718. doi: 10.1053/j.gastro.2018.05.025. Epub 2018 May 17.

    PubMed 29778606

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing avatrombopag (lower baseline platelet count) and avatrombopag (higher baseline platelet count) in people with Thrombocytopenia Associated With Liver Disease, run by Eisai Inc. at 109 sites in 20 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 109 sites in United States, South Korea, Hungary, Italy, France and 15 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Who Did Not Require a Platelet Transfusion or Any Rescue Procedure for Bleeding After Randomization Following a Scheduled Procedure (time frame: Baseline (Visit 2) up to 7 days following a scheduled procedure). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01972529, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2018.

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