A randomized controlled trial of lusutrombopag in Japanese patients with chronic liver disease undergoing radiofrequency ablation

Abstract

BackgroundThrombocytopenia represents an obstacle for invasive procedures in chronic liver disease (CLD) patients. We aimed to estimate the appropriate dose and evaluate the efficacy and safety of lusutrombopag for the treatment of thrombocytopenia before percutaneous liver radiofrequency ablation (RFA) for primary hepatic cancer in patients with CLD.MethodsIn this multicenter, randomized, double-blind, placebo-controlled study conducted in Japan, 61 CLD patients with platelet count < 50 × 103/µL at screening were randomized to placebo or lusutrombopag 2, 3, or 4 mg once daily for 7 days, followed by a 28-day post-treatment assessment period. The primary efficacy endpoint was the proportion of patients who did not require platelet transfusion before RFA. The pre-specified key secondary efficacy endpoint was the proportion of responders. Adverse events (AEs) and thrombosis-related AEs were evaluated.ResultsThe proportion of patients who did not require platelet transfusion before RFA and that of responders were significantly higher (p < 0.01) in the 2-mg (80.0, 66.7%), 3-mg (81.3, 68.8%), and 4-mg groups (93.3, 80.0%) compared with the placebo group (20.0, 6.7%) and showed a dose-dependent effect. The incidence of AEs was 97.8 and 100% in the lusutrombopag (all groups) and placebo groups, respectively; no dose-related increase was observed. Four patients experienced thrombosis-related events (one each in the placebo and 2-mg groups, and two in the 4-mg group). A total of 16 (18%) adverse drug reactions occurred in the safety analysis set.ConclusionsLusutrombopag 3 mg once daily for 7 days was effective without raising concerns about excessive increases in platelet count.Clinical trial registrationThe study is registered at JapicCTI-121944.Electronic supplementary materialThe online version of this article (10.1007/s00535-018-1499-2) contains supplementary material, which is available to authorized users.

Safety and effectiveness of lusutrombopag in Japanese chronic liver disease patients with thrombocytopenia undergoing invasive procedures: Interim results of a postmarketing surveillance

“…Given the variability across the clinical studies and this surveillance, such as differences in study design and patient enrollment criteria, it is difficult to directly compare the present surveillance results with those of the L‐PLUS studies. Nevertheless, despite the differences in characteristics between patients enrolled in the clinical trials compared with the present surveillance, it is reassuring that the present results confirm the safety and effectiveness of lusutrombopag, and further validate the results of the clinical trials . These interim results are also consistent with other recent reports of the safety and effectiveness of lusutrombopag in both treatment‐naïve and retreatment patients …”

“…All 21 patients who received a second or third round of treatment with lusutrombopag avoided platelet transfusion before their invasive procedure. Contrary to the protocols of the clinical trials of lusutrombopag, 26 patients did not receive platelet transfusion, despite having a platelet count <50 × 10 9 /L before the procedure. This was based on a decision by their physician, as per routine clinical practice.…”

“…In this surveillance, only one patient with a baseline platelet count ≥50 × 10 9 /L experienced a thrombus‐related AE. Furthermore, 10.9% of patients in our surveillance population had a current thrombosis/thromboembolism or a history of thrombosis/thromboembolism, although such patients were excluded in the prior clinical trials . Of patients who had a current thrombosis/thromboembolism or a history of thrombosis/thromboembolism, only one developed portal vein thrombosis (aggravation of portal vein thrombosis).…”

“…Data from multicenter, randomized, double‐blind, placebo‐controlled, clinical trials showed that lusutrombopag significantly reduced the proportion of patients with CLD who required platelet transfusion before invasive procedures ( P < 0.01 vs. placebo) . In the lusutrombopag treatment group of the phase 3 L‐PLUS 1 trial, the median platelet count increased to ≥50 × 10 9 /L after 5 days, and the mean time to reach maximum platelet count was 13.4 days .…”

Role of severe thrombocytopenia in preventing platelet count recovery in thrombocytopenic patients with chronic liver disease

“…4 However, patients who undergo transfusions can face certain complications including febrile nonhemolytic allergic reactions or infections. 4 However, patients who undergo transfusions can face certain complications including febrile nonhemolytic allergic reactions or infections.…”