Journal Article

Multicentre, double-blind, randomised, placebo-controlled study on the prophylactic use of naldemedine for opioid-induced nausea and vomiting in patients with cancer (POSEIDON study): a protocol paper

Kurihashi, Takeo, Hokabe, Mitsuki, Ogihara, Suguru, Oyamada, Shunsuke, Ohira, Mayumi, Takahashi, Kota, Uneno, Yu, Kataoka, Shigeki, Ishihara, Yo, Kida, Masaki, Hamano, Jun, Sonoyama, Takuhiro, Yoshino, Sadaaki, Morita, Tatsuya, Kessoku, Takaomi, Koretaka, Yuichi, Hirakawa, Mami, Satomi, Eriko, Kosugi, Kazuhiro, Kajiura, Shinya, Tomita, Naoki, Iwashita, Kohei, Higashibata, Takahiro, Nakajima, Atsushi

2026

Overview

IntroductionOpioid-induced nausea and vomiting (OINV) in patients with cancer imposes a substantial clinical burden and may compromise adherence to opioid therapy. Naldemedine, a peripheral μ-opioid receptor antagonist, is currently approved for the treatment of opioid-induced constipation. Recent evidence suggests similar benefits for the treatment of OINV. This study aims to evaluate the preventive effect of naldemedine on OINV in patients with cancer pain initiating opioid analgesics.Methods and analysisThis multicentre, double-blind, randomised, placebo-controlled, parallel-group comparison trial will be conducted across 20 hospitals and clinics in Japan. An estimated 120 patients with cancer scheduled to initiate opioid analgesic therapy will be recruited and randomly assigned (1:1) to receive either naldemedine or placebo on day 1 (visit 1). From days 1 to 7, patients will receive blinded study medication concurrently with opioid analgesics and will be followed for 8 days. The primary endpoint will be the proportion of patients achieving a complete response (CR) on day 5, defined as no vomiting and no use of rescue antiemetics for up to 120 hours after initiation of opioid analgesics. Key secondary endpoints will include the proportion of patients achieving CR on days 1, 2, 3 and 7; changes in Numerical Rating Scale scores from baseline; duration of nausea; proportion of patients who experience vomiting; proportion of patients using rescue antiemetics and frequency of rescue antiemetic use. Additionally, the incidence of adverse events and serious adverse events will be recorded throughout the observation period.Ethics and disseminationThis study has been reviewed and approved by the Hattori Clinic Certified Review Board (approval number: CRB3180027). Written informed consent will be obtained from all participating patients before study commencement. The results of the study will be presented at academic conferences in Japan or overseas and submitted for publication in a peer-reviewed journal.Trial registration numberNCT07038551 and jRCTs031250128.

• Publisher: British Medical Journal Publishing Group,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Adult / Analgesics / Analgesics, Opioid - adverse effects / Antiemetics / Antiemetics - therapeutic use / Antipsychotics / Cancer pain / Cancer Pain - drug therapy / Cancer therapies / Chemotherapy / Clinical trials / Constipation / Data centers / Double-Blind Method / Drug withdrawal / Electrocardiography / Female / Gastroenterology and Hepatology / Histamine / Humans / Informed consent / Japan / Male / Middle Aged / Morphine / Multicenter Studies as Topic / Naltrexone - administration & dosage / Naltrexone - analogs & derivatives / Naltrexone - therapeutic use / Narcotic Antagonists - therapeutic use / Narcotics / Nausea / Nausea - chemically induced / Nausea - prevention & control / Neoplasms - complications / Pain / Palliative care / Participation / Patient-reported outcome measures / Patients / Preventive medicine / Protocol / Psychotropic drugs / Randomized controlled trial / Randomized Controlled Trials as Topic / Serotonin / Side effects / Specialty products / Steroids / Vomiting / Vomiting - chemically induced / Vomiting - prevention & control