Eltrombopag trial halted after thrombotic events in patients with liver disease, thrombocytopenia
Thrombopoietin-receptor agonist eltrombopag may have increased the risk for portal vein thrombosis among patients with chronic liver disease and thrombocytopenia, causing the early termination of an efficacy study.
In a double blind, placebo-controlled, international trial, researchers randomly assigned 292 patients with chronic liver disease and a platelet count less than 50,000/mm3 to receive either 75 mg eltrombopag (n=145) or placebo (n=147) daily for 14 days prior to an elective, invasive procedure. Evaluated factors included platelet counts and the number of platelet transfusions performed before, during or up to 30 days after the procedure, as well as incidences of bleeding of WHO grade 2 or higher during the study.
In the treated group, 104 participants did not require a platelet transfusion within the specified time period, compared with 28 in the placebo group (P<.001). Among those who received transfusions, the median number of transfused units was smaller in treated patients (3.0 vs. 4.0). Platelet counts were greater than 80,000/mm3 in 59% of patients after 2 weeks of treatment, compared with 5% in the placebo group. Bleeding occurred in 17% of treated patients and 23% of placebo patients, with no statistical significance for the difference.
The study was terminated early after six treated participants experienced thrombotic events related to the portal venous system, compared with one placebo patient. Thrombotic events were significantly more common among treated patients (OR=3.04; 95% CI, 0.62-14.82), and increased risk was associated with platelet counts greater than 200,000/mm3.
Other than the thromboses, no significant difference was observed between groups for incidence or severity of adverse events. Common events included headache, pyrexia, abdominal pain, diarrhea, nausea and hepatic encephalopathy.
“Further exploration of eltrombopag therapy is required, including better identification of risk factors for the development of thrombosis, dose optimization and careful patient selection,” the researchers concluded. “Until such studies have been conducted, eltrombopag is not recommended as an alternative to platelet transfusion in patients with chronic liver disease and thrombocytopenia who are undergoing an elective invasive procedure.”
Disclosure: See the study for a full list of relevant disclosures.