WEUSKOP5410: Observational Study in ENABLE Clinical Trials

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT01458080

Collaborator

(none)

Enrollment

30.1

Duration (Months)

Study Details

Study Description

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	Phase
Hepatitis C	Drug: eltrombopag

Study Design

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 1, 2011

Actual Primary Completion Date :

Nov 1, 2013

Actual Study Completion Date :

Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Patients w/secondary thrombocytopenia related to hepatitis C Patients w/secondary thrombocytopenia related to hepatitis C	Drug: eltrombopag eltrombopag

Arm

Intervention/Treatment

Patients w/secondary thrombocytopenia related to hepatitis C

Drug: eltrombopag

eltrombopag

Outcome Measures

Primary Outcome Measures

diagnosis of a thromboembolic event during the study period. [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.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.