Phase III, international, multicentre, double-blind, dose increment, parallel-arm, randomised controlled trial of duloxetine versus pregabalin for opioid-unresponsive neuropathic cancer pain.
Authors: Matsuoka Hiromichi , Clark Katherine , Fazekas Belinda , Oyamada Shunsuke , Brown Linda , Ishiki Hiroto , Matsuda Yoshinobu , Hasuo Hideaki , Ariyoshi Keisuke , Lee Jessica , Le Brian H. , Fujiwara Noriko , Miyaji Tempei , Agar Meera Ruth , Yamaguchi Takuhiro , Satomi Eriko , Iwase Satoru , Phillips Jane , Koyama Atsuko , Currow David Christopher ,   Improving Palliative, Aged and Chronic Care through Clinical Research and Translation
Published: June 2023

TPS12146 Background: Management of neuropathic cancer pain (NCP) refractory to regular opioids remains an important challenge. The efficacy of pregabalin for NCP except chemotherapy-induced peripheral neuropathy has already been confirmed in two randomised controlled trials (RCTs) compared with placebo. Duloxetine offers the potential of analgesia in opioid refractory NCP. However, there are no RCT of duloxetine for the management of opioid-refractory NCP as a first line treatment. Both classes of drugs have the potential to reduce NCP, but there has been no head-to-head comparison for the efficacy and safety, especially given differing side effect profiles. Methods: An international, multicentre, double-blind, dose increment, parallel-arm, RCT. Eligibility criteria include: adult cancer patients experiencing NCP refractory to opioids; Brief Pain Inventory (BPI)-item 3 (worst pain) ≥4; Neuropathic Pain on the Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale ≥12 despite of an adequate trial of regular opioid medication (≥60mg/day oral morphine equivalent dose). The study will recruit inpatients and outpatients in Japan and Australia. Participants will be randomised (1:1 allocation ratio) to duloxetine or pregabalin. Dose escalation is to day 14 and from day 14 to 21 is a dose de-escalation period to avoid withdrawal effects. Dose escalation schedule in each-arm is shown in Table 1. The primary endpoint is the mean difference in BPI item 3 over the previous 24 hours on day 14 between groups. Null hypothesis is there is no difference in BPI item 3 in the previous 24 hours on day 14 between both groups for patients with opioid refractory NCP. Comparison of the BPI item 3 on day 14 between duloxetine groups and pregabalin groups will be conducted using a two-sided Student’s t-test at a significance level of 5% according to the intention-to-treat principle. Point estimates and 95% CIs for the difference between two groups will be calculated. A sample size of 160 participants is required with 67 subjects enrolled to date. The DSMC last reviewed the trial in December 2022 and case accumulation expected to be completed by the end of 2024. Table 1：Dose escalation schedule in each-arm. Duloxetine Arm Stage 1 (Day 1-3): Duloxetine (30 mg) 1 capsule (morning) and Placebo 1 capsule (bedtime) Stage 2 (Day 4-7): Same as Stage 1 Stage 3 (Day 8-14): Duloxetine (30 mg) 1 capsule twice a day (morning and bedtime). Pregabalin Arm Stage 1 (Day 1-3): Pregabalin (25 mg) 1 capsule twice a day (morning and bedtime). Stage 2 (Day 4-7): Pregabalin (75 mg) 1 capsule twice a day (morning and bedtime). Stage 3 (Day 8-14): Pregabalin (75 mg) 2 capsules (150 mg) twice a day (morning and bedtime). Clinical trial information: ACTRN12620000656932 , jRCTs051190087.