WEUSKOP5410: Observational Study in ENABLE Clinical Trials

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 evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01458080
Recruitment Status : Completed
First Posted : October 24, 2011
Last Update Posted : December 9, 2013
Information provided by (Responsible Party):

Brief Summary:
Hepatitis C Virus (HCV) is a leading cause of chronic liver disease (CLD) worldwide. Current mainstay of treatment is combination therapy with pegylated interferon and ribavarin. Thrombocytopenia as a treatment related adverse event or a complication of chronic liver disease often necessitates dose reduction and discontinuation in these patients. Revolade®/Promacta® (eltrombopag) is an oral second generation thrombopoietic growth factor in development for the treatment thrombocytopenia associated with various conditions, including secondary thrombocytopenia related to CLD and hepatitis C. In 2009 a phase III trial for CLD patients undergoing an elective invasive procedure (ELEVATE) was terminated early due to an imbalance of thromboembolic events (TEE) between the placebo and the eltrombopag arm. Currently, two global interventional Phase III trials (ENABLE 1 and ENABLE 2) are being conducted in approximately 1500 patients to evaluate the efficacy of eltrombopag in enabling HCV patients to achieve sustained viral response. Due to the similarities between the patient groups in ELEVATE and ENABLE, there is a concern that invasive procedures may influence the risk of TEE in the ENABLE population. This observational, non-interventional, retrospective, multicentre, nested case-control study will collect data from chart abstraction and medical record review to augment data from the ENABLE case report forms particularly with regards to invasive procedures. The study population includes cases and controls drawn from the ~1500 participants of the ENABLE trials. All eligible cases of TEE will be included in the study as cases. All other patients who participated in the ENABLE trials and did not experience a TEE, will be eligible to be selected as controls. Case report forms will be developed to enable standardized data capture. The Sponsor has contracted with the Clinical Research Organization, Outcome Sciences Inc to manage the study. ENABLE investigators will work with Outcome staff to obtain relevant information from the treating physician (e.g. surgeon) and the facility where the invasive procedure was performed (pre-operative tests, peri-operative course, diagnostic testing for TEE). Single point abstraction will be performed to obtain data from the medical record and from any additional data resources obtained by the investigator (e.g., operative note, anesthesia record). Analyses will be conducted using logistic regression models to estimate the risks. The primary objective of the study is to evaluate if there is an increased risk for TEE among patients who had an invasive procedure while exposed to eltrombopag (during the ENABLE trials).

Condition or disease Intervention/treatment
Hepatitis C Drug: eltrombopag

Study Type : Observational
Actual Enrollment : 1 participants
Observational Model: Case Control
Time Perspective: Retrospective
Official Title: WEUSKOP5410: A Retrospective Observational Non-Interventional Nested Case Control Study to Evaluate the Risk for Thromboembolic Events Associated With Surgery and Eltrombopag Exposure in the ENABLE Studies
Study Start Date : May 2011
Primary Completion Date : November 2013
Study Completion Date : November 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Eltrombopag
U.S. FDA Resources

Group/Cohort Intervention/treatment
Patients w/secondary thrombocytopenia related to hepatitis C
Patients w/secondary thrombocytopenia related to hepatitis C
Drug: eltrombopag

Primary Outcome Measures :
  1. diagnosis of a thromboembolic event during the study period. [ Time Frame: The patients will be followed from the time of entry into the ENABLE 1 or ENABLE 2 clinical trial up until the index date, defined as the time of event for the case. ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
The study population for this study comprised all patients who participated in both the open-label phase and the randomization phase of any of ENABLE 1 or ENABLE 2 clinical trials.

- The inclusion criteria for this case-control study was that the patients had to be participating in both the open-label phase and the randomization phase of any of ENABLE 1 or ENABLE 2 clinical trials.

Inclusion criteria for the ENABLE clinical trials included

  • age>18 years
  • evidence of chronic HCV infection
  • candidates for peg-interferon and ribavirin combination antiviral therapy
  • baseline platelet count of <75,000/µl
  • no significant anemia or neutropenia.

Exclusion criteria for the ENABLE clinical trial included:

  • non-responders to previous treatment with peg-interferon and ribavirin unless due to thrombocytopenia
  • decompensated liver disease, e.g. Child-Pugh score >6 or history of ascites or hepatic encephalopathy or current evidence of ascites
  • serious cardiac, cerebrovascular, or pulmonary disease
  • documented history of clinically significant bleeding from oesophageal or gastric varices, haemoglobinopathies, e.g. sickle cell anemia, thalassemia major, history of arterial or venous thrombosis, hepatocellular carcinoma, Human Immunodeficiency Virus (HIV) or Hepatitis B infection
  • any disease condition associated with active bleeding or requiring anticoagulation
  • history of malignancy, history of alcohol/drug abuse or dependence within 6 months of the study start
  • history of platelet clumping that prevents reliable measurement of platelet counts
  • history of major organ transplantation with an existing functional graft
  • evidence of portal vein thrombosis on abdominal imaging within 3 months of the baseline visit.

No additional exclusion criteria were applied to the case-control study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01458080

Sponsors and Collaborators
Study Director: GSK Clinical Trials GlaxoSmithKline

Responsible Party: GlaxoSmithKline Identifier: NCT01458080     History of Changes
Other Study ID Numbers: 115885
EPI40664 ( Other Identifier: GSK )
WEUSKOP5410 ( Other Identifier: GSK )
First Posted: October 24, 2011    Key Record Dates
Last Update Posted: December 9, 2013
Last Verified: December 2013

Keywords provided by GlaxoSmithKline:
invasive procedures
Thromboembolic events
Hepatitis C

Additional relevant MeSH terms:
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases