Eltrombopag To Reduce The Need For Platelet Transfusion In Subjects With Chronic Liver Disease And Thrombocytopenia Undergoing Elective Invasive Procedures

NCT00678587 | Terminated Phase 3 Results DMC

• 1 other identifier: TPL104054
• Study Type: interventional
• Target: 292
• Locations: 13 countries
• Sites: 107

Brief Summary

The purpose of this study is to assess the ability of eltrombopag to elevate platelet counts thereby reducing the need for platelet transfusions in chronic liver disease patients with thrombocytopenia undergoing elective invasive procedures. The clinical benefit of eltrombopag will be measured by the proportion of subjects who avoid platelet transfusions, before, during and up to 7 days after undergoing an invasive procedure. In addition, bleeding events will be monitored during this time. The number of transfusions, safety events and medical resource utilisation will be monitored during this time and for up to 30 days after undergoing an invasive procedure to help further evaluate clinical benefit.

Conditions

Non-alcoholic Steatohepatitis; Chronic Liver Disease; HCV; NASH - Nonalcoholic Steatohepatitis; HIV Infection; Thrombocytopenia; Hepatitis C Virus; HBV; Human Immunodeficiency Virus; Liver Diseases; Hepatitis B Virus

Keywords

elective invasive procedure.; platelet transfusion; chronic liver disease-related thrombocytopenia; platelets; thrombopoietin

Outcome Measures

Primary Outcomes (1)

• 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

  A platelet transfusion was given if the platelet count was \<50 giga (10\^9) per liter (Gi/L) before the procedure. A platelet transfusion was not given if the platelet count was \>80 Gi/L (based on a primary endpoint of success). For participants with platelet counts between 50 Gi/L and 80 Gi/L, platelet transfusions were administered at the discretion of the investigator and the physician performing the elective invasive procedure.

  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

Secondary Outcomes (15)

• Number of Participants With a World Health Organization (WHO) Bleeding Score >=2 During and up to 7 Days Following Elective Invasive Procedures

  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

• Number of Participants With the Indicated Number of Platelet Transfusions Administered

  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

• 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

  Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 day follow-up; early withdrawal; and maximum post-baseline

• 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

  Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 day follow-up; and maximum post-baseline

• Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category

  Screening to Procedure +30 day follow-up or early withdrawal

Study Arms (2)

Placebo

PLACEBO COMPARATOR

placebo, once daily, oral

Drug: Placebo

Active

ACTIVE COMPARATOR

75 mg, once daily, oral

Drug: Eltrombopag

Interventions

Eltrombopag DRUG

75 mg, once daily, oral

Active

Placebo DRUG

placebo, once daily, oral

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects, 18 years of age or more with chronic liver disease.
• Child-Pugh score of 12 or less.
• Model of End Stage Liver Disease (MELD) score of 24 or less.
• Subjects who, in the opinion of the investigator, are appropriate candidates to undergo an elective invasive procedure and who require a platelet transfusion to manage the risk of bleeding associated with the procedure.
• A baseline platelet count \<50,000/µL.
• A baseline serum sodium level \>130mEq/L.
• Haemoglobin concentration \>8g/dL stable for at least one month.
• A female is eligible to enter and participate in the study if she is of:
• Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including any female who:
• Has had a hysterectomy
• Has had a bilateral oophorectomy (ovariectomy)
• Has had a bilateral tubal ligation
• Is post-menopausal (demonstrate total cessation of menses for greater than one year)
• Childbearing potential, has a negative urine and/or serum pregnancy test at screening, and within the 24 hour period prior to the first dose of investigational product and uses one of the following acceptable methods of contraception:
• Complete abstinence from intercourse for two weeks before exposure to the study drug, throughout the clinical study, and for 28 days after completion or premature discontinuation from the study to account for the elimination of the study drug (minimum of 5 half-lives).

You may not qualify if:

• Subjects with a known hypersensitivity, intolerance or allergy to any of the ingredients in eltrombopag tablets.
• Evidence of portal vein thrombosis on abdominal imaging (ultrasound with Doppler or appropriate MRI/CT imaging techniques) within 3 months of study start.
• History of arterial or venous thrombosis, including Budd-Chiari Syndrome, AND ≥ two of the following risk factors: hereditary thrombophilic disorders (e.g. Factor V Leiden, ATIII deficiency, etc.), hormone replacement therapy, systemic contraception therapy (containing oestrogen), smoking, diabetes, hypercholesterolemia, medication for hypertension or cancer.
• Any disease condition associated with current active WHO Grade 3 or 4 bleeding.
• Active infection requiring systemic antibiotic therapy. Prophylactic use of antibiotics is permitted.
• Pregnant or nursing women.
• Treatment with an investigational drug within 30 days or five half-lives (whichever is longer) preceding the first dose of study medication.
• History of platelet agglutination abnormality that prevents reliable measurement of platelet counts.
• History of porphyria.
• Previous participation in TPL104054.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (107)

GSK Investigational Site

Birmingham, Alabama, 35294-0005, United States

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Scottsdale, Arizona, 85259, United States

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Little Rock, Arkansas, 72205-7199, United States

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Los Angeles, California, 90048, United States

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San Diego, California, 92103-8707, United States

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San Francisco, California, 94115, United States

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Denver, Colorado, 80262, United States

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Washington D.C., District of Columbia, 20307, United States

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Jacksonville, Florida, 32224, United States

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Miami, Florida, 33125, United States

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Miami, Florida, 33136, United States

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Chicago, Illinois, 60637, United States

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Indianapolis, Indiana, 46202, United States

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New Orleans, Louisiana, 70112, United States

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Baltimore, Maryland, 21202, United States

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Boston, Massachusetts, 02215, United States

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Burlington, Massachusetts, 01805, United States

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Ann Arbor, Michigan, 48109, United States

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Detroit, Michigan, 48202, United States

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New York, New York, 10021, United States

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Valhalla, New York, 10595, United States

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Charlotte, North Carolina, 28203, United States

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Durham, North Carolina, 27715, United States

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Portland, Oregon, 97239, United States

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Hershey, Pennsylvania, 17033-0850, United States

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Philadelphia, Pennsylvania, 19140, United States

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Charleston, South Carolina, 29425, United States

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Nashville, Tennessee, 37232, United States

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Dallas, Texas, 75235, United States

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Charlottesville, Virginia, 22908, United States

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Falls Church, Virginia, 22046, United States

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Richmond, Virginia, 23249, United States

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Richmond, Virginia, 23298, United States

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Capital Fefderal, Buenos Aires, Argentina

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Ciudad Autonoma de Buenos Aires, Buenos Aires, C1181ACI, Argentina

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Derqui, Pilar, Buenos Aires, B1629AHJ, Argentina

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Rosario, Santa Fe Province, S2002KDR, Argentina

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Buenos Aires, 1264, Argentina

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Brussels, 1070, Belgium

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Edegem, 2650, Belgium

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Ghent, 9000, Belgium

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Calgary, Alberta, T2N 4Z6, Canada

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Ottawa, Ontario, K1H 8L6, Canada

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Toronto, Ontario, M6H 3M1, Canada

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Montreal, Quebec, H2X 3J4, Canada

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Clermont Ferrand Cédex 1, 63058, France

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Lyon, 69288, France

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Lyon, 69437, France

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Marseille, 13385, France

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Montpellier, 34295, France

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Nice, 06202, France

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Paris, 75014, France

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Paris, 75571, France

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Paris, 75651, France

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Villejuif, 94804, France

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Jaipur, 302004, India

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Mumbai, 400 016, India

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Mumbai, 400020, India

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Bari, Apulia, 70124, Italy

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San Giovanni Rotondo (FG), Apulia, 71013, Italy

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Avellino, Campania, 83100, Italy

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Napoli, Campania, 80123, Italy

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Bologna, Emilia-Romagna, 40138, Italy

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Rome, Lazio, 00133, Italy

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Rome, Lazio, 00168, Italy

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Genoa, Liguria, 16132, Italy

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Milan, Lombardy, 20122, Italy

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Milan, Lombardy, 20132, Italy

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Milan, Lombardy, 20162, Italy

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Turin, Piedmont, 10126, Italy

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Palermo, Sicily, 90127, Italy

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Padua, Veneto, 35128, Italy

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Lahore, 54000, Pakistan

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Lahore, 54600, Pakistan

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Chorzów, 41-500, Poland

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Lubin, 59-301, Poland

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Słupsk, 76-200, Poland

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Warsaw, 01-201, Poland

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Wroclaw, 50-367, Poland

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Saint Petersburg, 194044, Russia

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Samara, 443011, Russia

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Smolensk, 214006, Russia

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Yekaterinburg, 620102, Russia

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GSK Investigational Site

Busan, 614-735, South Korea

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Incheon, 400-711, South Korea

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Seoul, 120-752, South Korea

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Seoul, 135-710, South Korea

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Seoul, 138-736, South Korea

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GSK Investigational Site

Barakaldo, 48903, Spain

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Barcelona, 08003, Spain

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Barcelona, 08025, Spain

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GSK Investigational Site

Barcelona, 08035, Spain

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Barcelona, 08036, Spain

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GSK Investigational Site

L'Hospitalet de Llobregat, 08907, Spain

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GSK Investigational Site

Madrid, 28007, Spain

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Madrid, 28034, Spain

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Málaga, 29010, Spain

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Oviedo, 33006, Spain

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Seville, 41013, Spain

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Valencia, 46009, Spain

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Valencia, 46014, Spain

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Valladolid, 47012, Spain

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GSK Investigational Site

Douliu, 640, Taiwan

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GSK Investigational Site

Kaohsiung City, 807, Taiwan

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Taipei, 100, Taiwan

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GSK Investigational Site

Taipei, 112, Taiwan

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GSK Investigational Site

Taoyuan District, Taiwan

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Related Publications (1)

• 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. doi: 10.1056/NEJMoa1110709.

  PMID: 22913681 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; HIV Infections; Thrombocytopenia; Hepatitis C; Acquired Immunodeficiency Syndrome; Liver Diseases; Hepatitis B; Jacobs syndrome

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Fatty Liver; Digestive System Diseases; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia; Hepatitis, Viral, Human; Flaviviridae Infections; Hepatitis; Slow Virus Diseases; Hepadnaviridae Infections; DNA Virus Infections

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2008
• First Posted: May 15, 2008
• Study Start: June 1, 2008
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: October 12, 2018
• Results First Posted: November 8, 2010

Record last verified: 2013-01

Locations

KR (5); TW (5); PL (5); AR (5); CA (4); FR (10); IT (14); RU (4); ES (14); IN (3); BE (3); PA (2); US (33)