Clinical benefit of midodrine hydrochloride in symptomatic orthostatic hypotension: a phase 4, double-blind, placebo-controlled, randomized, tilt-table study.
Clinical benefit of midodrine hydrochloride in symptomatic orthostatic hypotension: a phase 4, double-blind, placebo-controlled, randomized, tilt-table study.
复制标题
DOI：
10.1007/s10286-016-0363-9
复制
发表时间：
2016-08
期刊：
影响因子：
--
通讯作者：
Martin P
中科院分区：
文献类型：
--
作者：
Smith W;Wan H;Much D;Robinson AG;Martin P
盐酸米多君是一种短效升压剂，可使直立性低血压患者的血压升高。美国食品和药物管理局的H分部批准最初批准了米多君，要求上市后研究证实米多君在这一适应症中的临床益处。本研究的目的是评估米多君在症状反应方面的临床益处。这是一项双盲、安慰剂对照、随机、交叉、多中心研究(NCT01518946)。筛查后，年龄在18岁以下、有严重症状性直立性低血压并服用稳定剂量米多君至少3个月的患者被随机分成两组，第一天接受先前剂量的米多君或安慰剂治疗，第二天接受相应的替代治疗。主要终点在服药后1小时用45分钟的倾斜试验测量出现晕厥症状或近晕厥的时间。33名患者被纳入筛选：19名患者接受了至少一剂米多君，并在服药后至少进行了一次主要终点的测量。倾斜后出现晕厥症状或近乎晕厥的最小二乘平均时间(均数±标准误)S为1626.6±186.8，安慰剂为1105.6±186.8(差异：S 521.0；95%可信区间124.2-971.7；P=0.0131)。在10名患者中有15个不良事件；所有这些事件的严重程度都是轻微或中度的，调查人员认为没有一个与米多君有关。米多君是一种耐受性良好且临床有效的治疗症状性直立性低血压的药物。
Midodrine hydrochloride is a short-acting pressor agent that raises blood pressure in the upright position in patients with orthostatic hypotension. The US Food and Drug Administration’s Subpart H approval, under which midodrine was initially approved, requires post-marketing studies to confirm midodrine’s clinical benefit in this indication. The purpose of this study was to evaluate the clinical benefit of midodrine with regard to symptom response. This was a double-blind, placebo-controlled, randomized, crossover, multicenter study (NCT01518946). Following screening, patients aged ≥18 years with severe symptomatic orthostatic hypotension and on a stable dose of midodrine for at least 3 months were randomized to treatment with either their previous midodrine dose or placebo on day 1 and the respective alternate treatment on day 2. The primary endpoint measured time to syncopal symptoms or near-syncope using a 45-min tilt-table test at 1 h post-dose. Thirty-three patients were screened for inclusion: 19 received at least one dose of midodrine and had at least one post-dose measurement of the primary endpoint. The least-squares mean time to syncopal symptoms or near-syncope after tilt-table initiation (mean ± standard error) was 1626.6 ± 186.8 s for midodrine and 1105.6 ± 186.8 s for placebo (difference, 521.0 s; 95 % confidence interval 124.2–971.7 s; p = 0.0131). There were 15 adverse events in 10 patients; all of these were mild or moderate in severity, with none considered by the investigators to be related to midodrine. Midodrine is a well-tolerated and clinically effective treatment for symptomatic orthostatic hypotension.