Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia.
BACKGROUND
Eltrombopag is an oral thrombopoietin-receptor agonist. This study evaluated the efficacy of eltrombopag for increasing platelet counts and reducing the need for platelet transfusions in patients with thrombocytopenia and chronic liver disease who are undergoing an elective invasive procedure.


METHODS
We randomly assigned 292 patients with chronic liver disease of diverse causes and platelet counts of less than 50,000 per cubic millimeter to receive eltrombopag, at a dose of 75 mg daily, or placebo for 14 days before a planned elective invasive procedure that was performed within 5 days after the last dose. The primary end point was the avoidance of a platelet transfusion before, during, and up to 7 days after the procedure. A key secondary end point was the occurrence of bleeding (World Health Organization [WHO] grade 2 or higher) during this period.


RESULTS
A platelet transfusion was avoided in 104 of 145 patients who received eltrombopag (72%) and in 28 of 147 who received placebo (19%) (P<0.001). No significant difference between the eltrombopag and placebo groups was observed in bleeding episodes of WHO grade 2 or higher, which were reported in 17% and 23% of patients, respectively. Thrombotic events of the portal venous system were observed in 6 patients who received eltrombopag, as compared with 1 who received placebo, resulting in the early termination of the study. The incidence and severity of other adverse events were similar in the eltrombopag and placebo groups.


CONCLUSIONS
Eltrombopag reduced the need for platelet transfusions in patients with chronic liver disease who were undergoing elective invasive procedures, but it was associated with an increased incidence of portal-vein thrombosis, as compared with placebo. (Funded by GlaxoSmithKline; ELEVATE ClinicalTrials.gov number, NCT00678587.).
Division of Gastroenterology/Liver Center, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. nafdhal@bidmc.harvard.edu
Nezam H
NH
Afdhal
Edoardo G
EG
Giannini
Ghias
G
Tayyab
Aftab
A
Mohsin
Jin-Woo
JW
Lee
Angelo
A
Andriulli
Lennox
L
Jeffers
John
J
McHutchison
Pei-Jer
PJ
Chen
Kwang-Hyub
KH
Han
Fiona
F
Campbell
Denise
D
Hyde
Andres
A
Brainsky
Dickens
D
Theodore
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001565:Benzoates / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D004311:Double-Blind Method; D017558:Elective Surgical Procedures; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D006834:Hydrazines / Q000009:adverse effects / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D017713:Platelet Transfusion / Q000706:statistics & numerical data*; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D053628:Receptors, Thrombopoietin / Q000819:agonists* / Q000235:genetics; D013921:Thrombocytopenia / Q000150:complications*; D055815:Young Adult
D001565:Benzoates; D006834:Hydrazines; D011720:Pyrazoles; D053628:Receptors, Thrombopoietin; C520809:eltrombopag