Comparing the effectiveness of magnesium oxide and naldemedine in preventing opioid-induced constipation: A proof of concept, single institutional, two arm, open-label, phase II, randomized controlled trial: the MAGNET study
Patients taking opioids are known to develop opioid-induced constipation (OIC), which reduces their quality of life (QOL). The aim of this study is to compare magnesium oxide to naldemedine and determine which is more effective in preventing OIC. Methods: This is a proof of concept, prospective, randomized controlled trial, that commenced in Japan in March 2018. Initially, a questionnaire-based survey will be conducted targeting adult cancer patients who had concomitantly commenced opioid and
... menced opioid and OIC prevention treatment. Patients will then be randomly allocated to magnesium oxide (500 mg, thrice daily) or naldemedine (0.2 mg, once daily) groups. Each drug will be orally administrated for 12 weeks. The primary endpoint is defined as any improvement in the Japanese version of Patient Assessment of Constipation Quality of Life (JPAC-QOL) scores from the baseline to 2 weeks of treatment. Discussion : The primary endpoint is changes in the JPAC-QOL scores from the baseline to 2 weeks of intervention. The key secondary endpoint will be changes in spontaneous bowel movements (SBMs) at 2 and 12 weeks of intervention. This study will determine whether magnesium oxide or naldemedine is more effective for the prevention of OIC. Trial registration: This trial is registered in the Background Opioids are used for cancer pain management [1,2]; however, there are challenges associated with continuous opioid therapy owing to complications such as nausea, constipation, sleepiness, and respiratory depression     . Constipation develops in 15-64% of patients receiving strong opioid analgesics     and chronic constipation may occur at a higher incidence in women (men:women, 1:2.2) and older persons . In patients with various cancers in Japan, the cumulative incidence of opioid-induced constipation (OIC) is lung, 48%; pancreatic, 53%; colon, 60%; breast, 79%; stomach, 71%; esophageal, 60%, prostate, 50%; bladder, 50%; and others, 59%  . Long duration of opioid therapy is largely responsible for OIC  and drug tolerance against OIC is rarely established, so References 1 Gisondi P, Conti A, Galdo G, Piaserico S, De Simone C, Girolomoni G. Ustekinumab does not increase body mass index in patients with chronic plaque psoriasis: a prospective cohort study. Br J Dermatol. (12)70040-2. Yotoku M, Nakanishi A, Kanematsu M, Sakaguchi N, Hashimoto N, Koyama F, et al. Reduction of opioid side effects by prophylactic measures of palliative care team may result in improved quality of life.