Session Title: Parallel Session:
Presentation Date: Apr 17, 2010
ELTROMBOPAG IN CHRONIC LIVER DISEASE PATIENTS WITH THROMBOCYTOPENIA UNDERGOING AN ELECTIVE INVASIVE PROCEDURE: RESULTS FROM ELEVATE, A RANDOMISED CLINICAL TRIAL
N. Afdhal1, E. Giannini2, G.N. Tayyab3, A. Mohsin4, J.W. Lee5, A. Andriulli6, L. Jeffers7, J. McHutchison8, F. Campbell9, N. Blackman10, D. Hyde9, A. Brainsky11, D. Theodore12
1Division of Gastroenterology/Liver Center, Beth Israel Deaconess Medical Center, Boston, MA, USA, 2Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy, 3Department of Medicine/Gastroenterology & Hepatology, Post Graduate Medical Institute & Lahore General Hospital, 4Department of Gastroenterology, Services Hospital Lahore, Services Institute of Medical Sciences, Lahore, Pakistan, 5Department of Internal Medicine, Inha University Hospital and School of Medicine, Incheon, Republic of Korea, 6Department of Internal Medicine Division of Gastroenterology, Casa Sollievo Sofferenza Hospital, San Giovanni Rotondo, Italy, 7Center for Liver Diseases, University of Miami, Miller School of Medicine, Miami, FL, 8Division of Gastroenterology, Duke University Medical Center, Durham, NC, USA, 9Clinical Development, GlaxoSmithKline, Stockley Park, Uxbridge, UK, 10Biometrics and Epidemiology, 11Clinical Development, GlaxoSmithKline, Collegeville, PA, 12Clinical Development, GlaxoSmithKline, Research Triangle Park, NC, USA. *email@example.com
Background and Aims: Eltrombopag, an orally active thrombopoietin-receptor agonist, has been shown to increase platelet count in patients with liver disease. This study evaluated the effects of eltrombopag in reducing the need for platelet transfusion in thrombocytopenic subjects with chronic liver disease (CLD) undergoing an elective invasive procedure.
Methods: CLD subjects (Child-Pugh ≤12, MELD ≤24) with platelets < 50,000/uL were stratified (according to bleeding risk of planned procedure) and randomised (1:1) to eltrombopag-75mg or placebo once daily for 14 days prior to their planned invasive procedure which was performed within 5 days of last dose of eltrombopag. The primary endpoint was the proportion of subjects avoiding platelet transfusion before, during and up to 7 days post-procedure. Secondary endpoints included bleeding events, platelet counts and laboratory assessments up to 30 days post-procedure.
Results: Subjects (n=292) were well matched at baseline (61% Caucasian, 64% male, median age 53 years). A platelet transfusion was avoided in 104 (72%) eltrombopag versus 28 (19%) placebo subjects, thus meeting the primary endpoint (p < 0.0001). Bleeding events were reported in 25 (17%) eltrombopag versus 34 (23%) of placebo subjects. Average platelet count at day 14 was 103,000/uL in the eltrombopag group versus 39,000/uL in placebo (p < 0.0001).
Overall adverse events (AEs) were reported in 55% eltrombopag versus 59% placebo subjects. Incidence of serious adverse events was similar in both groups (13% eltrombopag, 12% placebo). Most common AEs were headache, pyrexia, abdominal pain, diarrhoea and nausea. Six subjects reported thrombotic events in eltrombopag versus two subjects in placebo [OR (95% CI) 2.827 (0.695, 11.501)].
All except one event, in the placebo group, occurred in the portal vein system. Due to the observed incidence of thrombotic events, GSK terminated ELEVATE early to allow a complete analysis of the study data.
Conclusions: Eltrombopag raised platelets and significantly reduced the proportion of subjects with CLD who required a platelet transfusion related to an invasive procedure. More thrombotic events in the portal vein system were reported in the eltrombopag arm. Analyses are ongoing to better characterize the safety and efficacy profile in this population with chronic liver disease.