Hisashi Hidaka1, Masayuki Kurosaki2, Hironori Tanaka3, Masatoshi Kudo4, Seigo Abiru5, Takumi Igura6, Toru Ishikawa7, Masataka Seike8, Takayuki Katsube9, Toshimitsu Ochiai9, Kazuhiro Kimura9, Takahiro Fukuhara9, Takeshi Kano9, Tsutae Nagata9, Katsuaki Tanaka10, Mineo Kurokawa11, Kazuhide Yamamoto12, Yukio Osaki13, Namiki Izumi2, Michio Imawari14. 1. Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan. Electronic address: hisashi7@kitasato-u.ac.jp. 2. Department of Gastroenterology and Hepatology, Japanese Red Cross Society Musashino Hospital, Musashino, Japan. 3. Internal Medicine, Hyogo College of Medicine Hospital, Nishinomiya, Japan. 4. Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osakasayama, Japan. 5. Department of Hepatology, National Hospital Organization Nagasaki Medical Center, Omura, Japan. 6. Department of Gastroenterology, Ikeda Municipal Hospital, Ikeda, Japan. 7. Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata, Japan. 8. Department of Gastroenterology, Oita University Hospital, Yufu, Japan. 9. Shionogi & Co, Ltd, Osaka, Japan. 10. Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan. 11. Department of Hematology and Oncology, The University of Tokyo Hospital, Tokyo, Japan. 12. Department of Internal Medicine, Okayama University Hospital, Okayama, Japan. 13. Japanese Red Cross Society Osaka Hospital, Osaka, Japan. 14. Institute for Gastrointestinal and Liver Diseases, Shin-yurigaoka General Hospital, Kawasaki, Japan.
Abstract
BACKGROUND & AIMS: Platelet transfusion is used to prevent hemorrhagic events in patients with thrombocytopenia undergoing invasive procedures, but there are many disadvantages. We evaluated the efficacy and safety of lusutrombopag in patients with chronic liver disease and thrombocytopenia undergoing invasive procedures. METHODS: We performed a double-blind, parallel-group, phase 3 study of 96 patients with chronic liver disease and thrombocytopenia (platelet counts below 50,000/μL) undergoing invasive procedures from October 2013 to May 2014 at 81 centers in Japan. Patients were randomly assigned (1:1) to groups given once-daily lusutrombopag (3 mg) or placebo for up to 7 days. The primary efficacy endpoint was the proportion of patients not requiring platelet transfusion before the invasive procedure. The protocol-defined response (platelet count 50,000/μL or more with an increase of 20,000/μL or more from baseline) and the time course of the change in platelet count were also evaluated. Adverse events were recorded. RESULTS: The proportions of patients who did not require preoperative platelet transfusion were 79.2% (38/48) in the lusutrombopag group and 12.5% (6/48) in the placebo group (P < .0001). A response was observed in 77.1% (37/48) of patients in the lusutrombopag group and 6.3% (3/48) of patients in the placebo group (P < .0001). In the lusutrombopag group without platelet transfusion, the median platelet count was 50,000/μL or more after 5 days; the mean time to reach the maximum platelet count was 13.4 days; and the number of days (adjusted mean) during which the platelet count was 50,000/μL or more was 21.09 days. Adverse drug reactions were reported in 8.3% of patients in the lusutrombopag group and 2.1% of patients in the placebo group. Two patients (1 per group) had a thrombotic event, but neither were associated with an excessive increase in platelet count (200,000/μL or more). CONCLUSION: In a placebo-controlled trial, lusutrombopag was effective in achieving and maintaining the target platelet count in patients with chronic liver disease and thrombocytopenia undergoing invasive procedures. No significant safety concerns were raised. Japanese clinical trial registration no: JapicCTI-132323.
RCT Entities:
BACKGROUND & AIMS: Platelet transfusion is used to prevent hemorrhagic events in patients with thrombocytopenia undergoing invasive procedures, but there are many disadvantages. We evaluated the efficacy and safety of lusutrombopag in patients with chronic liver disease and thrombocytopenia undergoing invasive procedures. METHODS: We performed a double-blind, parallel-group, phase 3 study of 96 patients with chronic liver disease and thrombocytopenia (platelet counts below 50,000/μL) undergoing invasive procedures from October 2013 to May 2014 at 81 centers in Japan. Patients were randomly assigned (1:1) to groups given once-daily lusutrombopag (3 mg) or placebo for up to 7 days. The primary efficacy endpoint was the proportion of patients not requiring platelet transfusion before the invasive procedure. The protocol-defined response (platelet count 50,000/μL or more with an increase of 20,000/μL or more from baseline) and the time course of the change in platelet count were also evaluated. Adverse events were recorded. RESULTS: The proportions of patients who did not require preoperative platelet transfusion were 79.2% (38/48) in the lusutrombopag group and 12.5% (6/48) in the placebo group (P < .0001). A response was observed in 77.1% (37/48) of patients in the lusutrombopag group and 6.3% (3/48) of patients in the placebo group (P < .0001). In the lusutrombopag group without platelet transfusion, the median platelet count was 50,000/μL or more after 5 days; the mean time to reach the maximum platelet count was 13.4 days; and the number of days (adjusted mean) during which the platelet count was 50,000/μL or more was 21.09 days. Adverse drug reactions were reported in 8.3% of patients in the lusutrombopag group and 2.1% of patients in the placebo group. Two patients (1 per group) had a thrombotic event, but neither were associated with an excessive increase in platelet count (200,000/μL or more). CONCLUSION: In a placebo-controlled trial, lusutrombopag was effective in achieving and maintaining the target platelet count in patients with chronic liver disease and thrombocytopenia undergoing invasive procedures. No significant safety concerns were raised. Japanese clinical trial registration no: JapicCTI-132323.