AzTrials
AzTrials

Thrombocytopenia Associated With Liver DiseasePhase 3NCT01976104

Treatment of Thrombocytopenia in Patients With Chronic Liver Disease Undergoing 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 120 sites in 17 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
204 participants
Where
120 sitesin 17 countries
Study dates
Nov 2013to 21 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 subjects
  • 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

120 sites in 17 countries.

120 sites in 17 countries

United States23 sites

  • Study site

    Baltimore, Maryland

  • Study site

    Birmingham, Alabama

  • Study site

    Boston, Massachusetts

  • Study site

    Charleston, South Carolina

  • Study site

    Charlottesville, Virginia

  • Study site

    Coronado, California

  • Study site

    Denver, Colorado

  • Study site

    Detroit, Michigan

  • Study site

    Houston, Texas

  • Study site

    Indianapolis, Indiana

  • Study site

    Kansas City, Kansas

  • Study site

    Kansas City, Missouri

  • Study site

    Little Rock, Arkansas

  • Study site

    Loma Linda, California

  • Study site

    Maywood, Illinois

  • Study site

    Miami, Florida

  • Study site

    New Orleans, Louisiana

  • Study site

    New York, New York

  • Study site

    Phoenix, Arizona

  • Study site

    Richmond, Virginia

  • Study site

    San Antonio, Texas

  • Study site

    Seattle, Washington

  • Study site

    Statesville, North Carolina

Other trials in United States

Japan19 sites

  • Study site

    Bunkyo-ku, Tokyo

  • Study site

    Chiba

  • Study site

    Chiyoda City, Tokyo

  • Study site

    Iruma, Saitama

  • Study site

    Morioka, Iwate

  • Study site

    Musashino, Tokyo

  • Study site

    Niigata

  • Study site

    Nishinomiya, Hyōgo

  • Study site

    Okayama, Okayama-ken

  • Study site

    Okayama

  • Study site

    Osaka, Osaka

  • Study site

    Osaka-Sayama-shi, Osaka

  • Study site

    Sapporo, Hokkaido

  • Study site

    Setagaya-ku, Tokyo

  • Study site

    Shinagawa-ku, Tokyo

  • Study site

    Takamatsu, Kagawa-ken

  • Study site

    Tokushima

  • Study site

    Wakayama

  • Study site

    Yufu, Oita Prefecture

Other trials in Japan

China8 sites

  • Study site

    Beijing, Beijing Municipality

  • Study site

    Chengdu, Sichuan

  • Study site

    Hangzhou, Zheijiang

  • Study site

    Hefei, Anhui

  • Study site

    Nanjing, Jiangsu

  • Study site

    Shijiazhuang, Hebei

  • Study site

    Xi'an, Shaanxi

  • Study site

    Xi’an, Shanxi

Other trials in China

Germany8 sites

  • Study site

    Bonn, North Rhine-Westphalia

  • Study site

    Frankfurt am Main, Hesse

  • Study site

    Hamburg

  • Study site

    Hanover, Lower Saxony

  • Study site

    Kiel, Schleswig-Holstein

  • Study site

    Leipzig, Saxony

  • Study site

    Mannheim, Baden-Wurttemberg

  • Study site

    Tübingen, Baden-Wurttemberg

Other trials in Germany

Israel8 sites

  • Study site

    Haifa

  • Study site

    Holon

  • Study site

    Jerusalem

  • Study site

    Nahariya

  • Study site

    Petah Tikva

  • Study site

    Ramat Gan

  • Study site

    Rehovot

  • Study site

    Tel Aviv

Other trials in Israel

Spain7 sites

  • Study site

    Barcelona

  • Study site

    Cáceres, Cáceres

  • Study site

    Girona

  • Study site

    L'Hospitalet de Llobregat, Barcelona

  • Study site

    Madrid

  • Study site

    Valencia

  • Study site

    Zaragoza

Other trials in Spain

Italy6 sites

  • Study site

    Baggiovara, Modena

  • Study site

    Florence

  • Study site

    Milan

  • Study site

    Pisa

  • Study site

    Roma

  • Study site

    Trento

Other trials in Italy

Romania6 sites

  • Study site

    Arad

  • Study site

    Bucharest

  • Study site

    Craiova

  • Study site

    Iași

  • Study site

    Sibiu

  • Study site

    Timișoara

Other trials in Romania

Czechia5 sites

  • Study site

    Brno

  • Study site

    Havířov

  • Study site

    Ostrava

  • Study site

    Prague

  • Study site

    Ústí nad Labem

Other trials in Czechia

France5 sites

  • Study site

    Clichy, Hauts De Seine

  • Study site

    Lyon, Rhone

  • Study site

    Nice, Alpes Maritimes

  • Study site

    Rennes, Ille Et Vilaine

  • Study site

    Villejuif, Val De Marne

Other trials in France

Mexico5 sites

  • Study site

    Durango

  • Study site

    Mérida, Yucatán

  • Study site

    Monterrey, Nuevo León

  • Study site

    Orizaba, Veracruz

  • Study site

    Zapopan, Jalisco

Other trials in Mexico

Australia4 sites

  • Study site

    Clayton, Victoria

  • Study site

    Footscray, Victoria

  • Study site

    Melbourne, Victoria

  • Study site

    Parkville, Victoria

Other trials in Australia

Brazil4 sites

  • Study site

    Aracaju

  • Study site

    Botucatu

  • Study site

    Porto Alegre

  • Study site

    Salvador

Other trials in Brazil

Russia4 sites

  • Study site

    Kemerovo

  • Study site

    Moscow

  • Study site

    Saint Petersburg

  • Study site

    Samara

Other trials in Russia

Argentina3 sites

  • Study site

    Ciudad Autonoma Buenos Aires

  • Study site

    Córdoba

  • Study site

    Rosario

Other trials in Argentina

Belgium3 sites

  • Study site

    Edegem

  • Study site

    Ghent

  • Study site

    Liège

Other trials in Belgium

Canada2 sites

  • Study site

    Calgary

  • Study site

    Edmonton

Other trials in Canada

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 NCT01976104
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 After Randomization and up to 7 Days 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: Randomization (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 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 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 Counts on 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 posted5 Nov 2013 (estimated)
  2. Study startNov 2013
  3. Primary completion30 Jan 2017
  4. Study completion21 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
204 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01976104
Sponsor's protocol ID
E5501-G000-311
Other IDs
2013-000934-36
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 120 sites in 17 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 120 sites in United States, Japan, China, Germany, Israel and 12 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 After Randomization and up to 7 Days Following a Scheduled Procedure (time frame: Randomization (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 NCT01976104, 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.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in