Abstract：
BACKGROUND: Among the different types of pain related to Parkinson\'s disease (PD), parkinsonian central pain (PCP) is the most disabling.
OBJECTIVE: We investigated the analgesic efficacy of two therapeutic strategies (opioid with oxycodone- prolonged-release (PR) and higher dose of levodopa/benserazide) compared with placebo in patients with PCP.
METHODS: OXYDOPA was a randomized, double-blind, double-dummy, placebo-controlled, multicenter parallel-group trial run at 15 centers within the French NS-Park network. PD patients with PCP (≥30 on the Visual Analogue Scale [VAS]) were randomly assigned to receive oxycodone-PR (up to 40 mg/day), levodopa/benserazide (up to 200 mg/day) or matching placebo three times a day (tid) for 8 weeks at a stable dose, in add-on to their current dopaminergic therapy. The primary endpoint was the change in average pain intensity over the previous week rated on VAS from baseline to week-10 based on modified intention-to-treat analyses.
RESULTS: Between May 2016 and August 2020, 66 patients were randomized to oxycodone-PR (n = 23), levodopa/benserazide (n = 20) or placebo (n = 23). The mean change in pain intensity was -17 ± 18.5 on oxycodone-PR, -8.3 ± 11.1 on levodopa/benserazide, and -14.3 ± 18.9 in the placebo groups. The absolute difference versus placebo was -1.54 (97.5% confidence interval [CI], -17.0 to 13.90; P = 0.8) on oxycodone-PR and +7.79 (97.5% CI, -4.99 to 20.58; P = 0.2) on levodopa/benserazide. Similar proportions of patients in each group experienced all-cause adverse events. Those leading to study discontinuation were most frequently observed with oxycodone-PR (39%) than levodopa/benserazide (5%) or placebo (15%).
CONCLUSIONS: The present trial failed to demonstrate the superiority of oxycodone-PR or a higher dose of levodopa in patients with PCP, while oxycodone-PR was poorly tolerated. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
OBJECTIVE: We investigated the analgesic efficacy of two therapeutic strategies (opioid with oxycodone- prolonged-release (PR) and higher dose of levodopa/benserazide) compared with placebo in patients with PCP.
METHODS: OXYDOPA was a randomized, double-blind, double-dummy, placebo-controlled, multicenter parallel-group trial run at 15 centers within the French NS-Park network. PD patients with PCP (≥30 on the Visual Analogue Scale [VAS]) were randomly assigned to receive oxycodone-PR (up to 40 mg/day), levodopa/benserazide (up to 200 mg/day) or matching placebo three times a day (tid) for 8 weeks at a stable dose, in add-on to their current dopaminergic therapy. The primary endpoint was the change in average pain intensity over the previous week rated on VAS from baseline to week-10 based on modified intention-to-treat analyses.
RESULTS: Between May 2016 and August 2020, 66 patients were randomized to oxycodone-PR (n = 23), levodopa/benserazide (n = 20) or placebo (n = 23). The mean change in pain intensity was -17 ± 18.5 on oxycodone-PR, -8.3 ± 11.1 on levodopa/benserazide, and -14.3 ± 18.9 in the placebo groups. The absolute difference versus placebo was -1.54 (97.5% confidence interval [CI], -17.0 to 13.90; P = 0.8) on oxycodone-PR and +7.79 (97.5% CI, -4.99 to 20.58; P = 0.2) on levodopa/benserazide. Similar proportions of patients in each group experienced all-cause adverse events. Those leading to study discontinuation were most frequently observed with oxycodone-PR (39%) than levodopa/benserazide (5%) or placebo (15%).
CONCLUSIONS: The present trial failed to demonstrate the superiority of oxycodone-PR or a higher dose of levodopa in patients with PCP, while oxycodone-PR was poorly tolerated. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
摘要：
背景：在与帕金森病（PD）相关的不同类型的疼痛中，帕金森中枢疼痛（PCP）是最致残的。
目的：我们研究了两种治疗策略（阿片类药物联合羟考酮缓释（PR）和更高剂量的左旋多巴/苄丝肼）与安慰剂在PCP患者中的镇痛效果。
方法：OXYDOPA是随机的，双盲,双假人,安慰剂对照,多中心平行组试验在法国NS-Park网络内的15个中心进行。患有PCP的PD患者（视觉模拟评分[VAS]≥30）被随机分配接受羟考酮PR（最多40mg/天），左旋多巴/苄丝肼（高达200毫克/天）或匹配的安慰剂，每天三次（tid），以稳定的剂量持续8周，作为他们目前多巴胺能治疗的补充。主要终点是根据改良的意向治疗分析，在VAS上从基线到第10周的前一周平均疼痛强度的变化。
结果：在2016年5月至2020年8月之间，66例患者随机接受羟考酮-PR（n=23），左旋多巴/苄丝肼（n=20）或安慰剂（n=23）。羟考酮-PR的疼痛强度平均变化为-17±18.5，左旋多巴/苄丝肼-8.3±11.1，安慰剂组的-14.3±18.9。与安慰剂相比，绝对差异为-1.54(97.5%置信区间[CI]，羟考酮PR为-17.0至13.90；P=0.8），左旋多巴/苄丝肼为+7.79（97.5％CI，-4.99至20.58；P=0.2）。每组中相似比例的患者经历了全因不良事件。与左旋多巴/苄丝肼（5％）或安慰剂（15％）相比，羟考酮PR（39％）最常观察到导致研究中止的那些。
结论：本试验未能证明羟考酮-PR或更高剂量的左旋多巴在PCP患者中的优越性，而羟考酮-PR的耐受性较差。©2024作者（S）。由WileyPeriodicalsLLC代表国际帕金森症和运动障碍协会出版的运动障碍。
目的：我们研究了两种治疗策略（阿片类药物联合羟考酮缓释（PR）和更高剂量的左旋多巴/苄丝肼）与安慰剂在PCP患者中的镇痛效果。
方法：OXYDOPA是随机的，双盲,双假人,安慰剂对照,多中心平行组试验在法国NS-Park网络内的15个中心进行。患有PCP的PD患者（视觉模拟评分[VAS]≥30）被随机分配接受羟考酮PR（最多40mg/天），左旋多巴/苄丝肼（高达200毫克/天）或匹配的安慰剂，每天三次（tid），以稳定的剂量持续8周，作为他们目前多巴胺能治疗的补充。主要终点是根据改良的意向治疗分析，在VAS上从基线到第10周的前一周平均疼痛强度的变化。
结果：在2016年5月至2020年8月之间，66例患者随机接受羟考酮-PR（n=23），左旋多巴/苄丝肼（n=20）或安慰剂（n=23）。羟考酮-PR的疼痛强度平均变化为-17±18.5，左旋多巴/苄丝肼-8.3±11.1，安慰剂组的-14.3±18.9。与安慰剂相比，绝对差异为-1.54(97.5%置信区间[CI]，羟考酮PR为-17.0至13.90；P=0.8），左旋多巴/苄丝肼为+7.79（97.5％CI，-4.99至20.58；P=0.2）。每组中相似比例的患者经历了全因不良事件。与左旋多巴/苄丝肼（5％）或安慰剂（15％）相比，羟考酮PR（39％）最常观察到导致研究中止的那些。
结论：本试验未能证明羟考酮-PR或更高剂量的左旋多巴在PCP患者中的优越性，而羟考酮-PR的耐受性较差。©2024作者（S）。由WileyPeriodicalsLLC代表国际帕金森症和运动障碍协会出版的运动障碍。
