Randomized withdrawal study of patients with symptomatic neurogenic orthostatic hypotension responsive to droxidopa.
Randomized withdrawal study of patients with symptomatic neurogenic orthostatic hypotension responsive to droxidopa.
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有症状性神经源性体性低血压患者的随机戒断研究反应了龙氧化疾病。
DOI：
10.1161/hypertensionaha.114.04035
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发表时间：
2015-01
期刊：
影响因子：
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通讯作者：
Droxidopa 302 Investigators
中科院分区：
文献类型：
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作者：
Biaggioni I;Freeman R;Mathias CJ;Low P;Hewitt LA;Kaufmann H;Droxidopa 302 Investigators
文本中提供了补充数字内容。我们评估了屈昔多巴（一种转化为去甲肾上腺素的前药）是否有益于治疗症状性神经源性直立性低血压，这种低血压是由于未能对姿势挑战产生适当的去甲肾上腺素反应而导致的。患有症状性神经源性直立性低血压和帕金森病、多系统萎缩、单纯自主神经衰竭或非糖尿病自主神经病变的患者接受开放标签屈昔多巴滴定（100-600 mg，每日 3 次）。然后，反应者按照其个体化剂量接受额外的 7 天开放标签治疗。随后患者被随机分配继续服用屈昔多巴或停药至安慰剂 14 天。然后，我们评估了患者报告的直立性低血压问卷评分和血压测量结果。从随机分组到研究结束（主要结果；N=101），直立性低血压问卷头晕/头晕评分的平均恶化程度，安慰剂组为 1.9±3.2，屈昔多巴组为 1.3±2.8 个单位（P=0.509）。其他 5 项直立性低血压问卷症状评分中的 4 项以及所有 4 项症状影响评分均支持屈昔多巴，这对于患者自我报告的短时间站立活动（P=0.033）和长时间站立活动（P=0.028）的能力具有统计学意义。此外，对所有症状的预定义综合评分（体位性低血压问卷综合）的事后分析表明屈昔多巴具有显着益处（P=0.013）。站立收缩压组间无显着差异（P=0.680）。屈昔多巴耐受性良好。总之，这项随机停药屈昔多巴研究未能达到其主要疗效终点。正如该试验积极的次要结果所表明的那样，需要进行更多的临床试验来证实屈昔多巴对症状性神经源性直立性低血压有益。网址：http://www.clinicaltrials.gov。唯一标识符：NCT00633880。
Supplemental Digital Content is available in the text. We evaluated whether droxidopa, a prodrug converted to norepinephrine, is beneficial in the treatment of symptomatic neurogenic orthostatic hypotension, which results from failure to generate an appropriate norepinephrine response to postural challenge. Patients with symptomatic neurogenic orthostatic hypotension and Parkinson disease, multiple system atrophy, pure autonomic failure, or nondiabetic autonomic neuropathy underwent open-label droxidopa titration (100–600 mg, 3× daily). Responders then received an additional 7-day open-label treatment at their individualized dose. Patients were subsequently randomized to continue with droxidopa or withdraw to placebo for 14 days. We then assessed patient-reported scores on the Orthostatic Hypotension Questionnaire and blood pressure measurements. Mean worsening of Orthostatic Hypotension Questionnaire dizziness/lightheadedness score from randomization to end of study (the primary outcome; N=101) was 1.9±3.2 with placebo and 1.3±2.8 units with droxidopa (P=0.509). Four of the other 5 Orthostatic Hypotension Questionnaire symptom scores and all 4 symptom-impact scores favored droxidopa, with statistical significance for the patient’s self-reported ability to perform activities requiring standing a short time (P=0.033) and standing a long time (P=0.028). Furthermore, a post hoc analysis of a predefined composite score of all symptoms (Orthostatic Hypotension Questionnaire composite) demonstrated a significant benefit for droxidopa (P=0.013). There was no significant difference between groups for standing systolic blood pressure (P=0.680). Droxidopa was well tolerated. In summary, this randomized withdrawal droxidopa study failed to meet its primary efficacy end point. Additional clinical trials are needed to confirm that droxidopa is beneficial in symptomatic neurogenic orthostatic hypotension, as suggested by the positive secondary outcomes of this trial. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00633880.