Hiroaki Fuji1, Etsuro Hatano2,3, Kohta Iguchi1, Kenya Yamanaka1, Tomoaki Yoh1, Yoshinobu Ikeno1, Satoru Seo1, Kojiro Taura1, Kentaro Yasuchika1, Shiro Tanaka4, Hisanari Ishii5, Mariko Kobayashi6, Kazuyuki Ueno6, Shinji Uemoto1. 1. Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 2. Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. shatano@hyo-med.ac.jp. 3. Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo, 663-8501, Japan. shatano@hyo-med.ac.jp. 4. Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan. 5. Department of Anesthesia, Tenri Hospital, Tenri, Japan. 6. Department of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Science, Niigata, Japan.
Abstract
PURPOSE: Post-hepatectomy liver failure is one of the most serious complications liver surgeons must overcome. We previously examined olprinone, a selective phosphodiesterase III inhibitor, and demonstrated its hepatoprotective effects in rats and pigs. We herein report the results of a phase I clinical trial of olprinone in liver surgery (UMIN000004975). METHODS: Twenty-three patients who underwent hepatectomy between 2011 and 2015 were prospectively registered. In the first 6 cases, olprinone (0.1 μg/kg/min) was administered for 24 h from the start of surgery. In the remaining 17 cases, olprinone (0.05 μg/kg/min) was administered from the start of surgery until just before the transection of the liver parenchyma. The primary endpoint was safety, and the secondary endpoint was efficacy. For the evaluation of efficacy, the incidence of post-hepatectomy liver failure in 20 hepatocellular carcinoma patients was externally compared with 20 propensity score-matched patients. RESULTS: No intraoperative side effects were observed, and the morbidity rates in the analyzed cohorts were acceptable. The rate of post-hepatectomy liver failure frequency tended to be lower in the olprinone group. CONCLUSIONS: The safety of olprinone in liver surgery was confirmed. The efficacy of olprinone will be re-evaluated in clinical trials.
PURPOSE: Post-hepatectomy liver failure is one of the most serious complications liver surgeons must overcome. We previously examined olprinone, a selective phosphodiesterase III inhibitor, and demonstrated its hepatoprotective effects in rats and pigs. We herein report the results of a phase I clinical trial of olprinone in liver surgery (UMIN000004975). METHODS: Twenty-three patients who underwent hepatectomy between 2011 and 2015 were prospectively registered. In the first 6 cases, olprinone (0.1 μg/kg/min) was administered for 24 h from the start of surgery. In the remaining 17 cases, olprinone (0.05 μg/kg/min) was administered from the start of surgery until just before the transection of the liver parenchyma. The primary endpoint was safety, and the secondary endpoint was efficacy. For the evaluation of efficacy, the incidence of post-hepatectomy liver failure in 20 hepatocellular carcinomapatients was externally compared with 20 propensity score-matched patients. RESULTS: No intraoperative side effects were observed, and the morbidity rates in the analyzed cohorts were acceptable. The rate of post-hepatectomy liver failure frequency tended to be lower in the olprinone group. CONCLUSIONS: The safety of olprinone in liver surgery was confirmed. The efficacy of olprinone will be re-evaluated in clinical trials.
Entities:
Keywords:
Olprinone; Phase I clinical trial; Post-hepatectomy liver failure; Selective phosphodiesterase III inhibitor; Translational research
Authors: Nuh N Rahbari; O James Garden; Robert Padbury; Mark Brooke-Smith; Michael Crawford; Rene Adam; Moritz Koch; Masatoshi Makuuchi; Ronald P Dematteo; Christopher Christophi; Simon Banting; Val Usatoff; Masato Nagino; Guy Maddern; Thomas J Hugh; Jean-Nicolas Vauthey; Paul Greig; Myrddin Rees; Yukihiro Yokoyama; Sheung Tat Fan; Yuji Nimura; Joan Figueras; Lorenzo Capussotti; Markus W Büchler; Jürgen Weitz Journal: Surgery Date: 2011-01-14 Impact factor: 3.982