乙酰唑胺在特发性颅内高压治疗试验中的安全性和耐受性

Safety and Tolerability of Acetazolamide in the Idiopathic Intracranial Hypertension Treatment Trial.

作者信息

ten Hove Martin W, Friedman Deborah I, Patel Anil D, Irrcher Isabella, Wall Michael, McDermott Michael P

机构信息

Department of Ophthalmology (MWtH, II), Queen's University and Hotel Dieu Hospital, Kingston, Ontario, Canada; Departments of Neurology and Neurotherapeutics and Ophthalmology (DIF), University of Texas Southwestern Medical Center, Dallas, Texas; Department of Ophthalmology (ADP), Dean McGee Eye Institute, University of Oklahoma, Oklahoma City, Oklahoma; Department of Neurology (MW), University of Iowa, Iowa City, Iowa; and Department of Biostatistics and Computational Biology (MPM), University of Rochester, Rochester, New York.

出版信息

J Neuroophthalmol. 2016 Mar;36(1):13-9. doi: 10.1097/WNO.0000000000000322.

DOI:10.1097/WNO.0000000000000322

PMID:26587993

Abstract

OBJECTIVE

To examine the tolerability and adverse events reported in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT).

METHODS

Randomized, double-masked, placebo-controlled clinical trial. Trial participants (n = 165) with mild visual loss concurrently receiving low-sodium weight-reduction diet plus the maximally tolerated dosage of acetazolamide (up to 4 g/d) or placebo for 6 months.

MAIN OUTCOMES MEASURES

adverse events (AEs), assessment of clinical and laboratory findings at study visits.

RESULTS

Thirty-eight of 86 participants randomized to the acetazolamide group (44.1%) tolerated the maximum allowed dosage of 4 g/d. The average time to achieve maximum study dosage in the acetazolamide group was 13 weeks (median 12 weeks; range 10-24 weeks). A total of 676 AEs (acetazolamide, n = 480; placebo, n = 196) and 9 serious AEs (acetazolamide, n = 6; placebo, n = 3) were reported. Notably, the percentages of participants reporting at least 1 AE in the nervous, gastrointestinal, metabolic, and renal organ systems were significantly higher in the acetazolamide group (P < 0.05). The odds of paresthesia (OR 9.82; 95% CI 3.87-27.82), dysgeusia (OR ∞; 95% CI 3.99-∞), vomiting and diarrhea (OR 4.11; 95% CI 1.04-23.41), nausea (OR 2.99; 95% CI 1.26-7.49) and fatigue (OR 16.48; 95% CI 2.39-702.40) were higher in the acetazolamide group than in the placebo group.

CONCLUSION

Acetazolamide appears to have an acceptable safety profile at dosages up to 4 g/d in the treatment of idiopathic intracranial hypertension. The majority of participants in the Idiopathic Intracranial Hypertension Treatment Trial were able to tolerate acetazolamide above 1 g/d for 6 months.

摘要

目的

研究特发性颅内高压治疗试验（IIHTT）中报告的耐受性和不良事件。

方法

随机、双盲、安慰剂对照临床试验。试验参与者（n = 165）有轻度视力丧失，同时接受低钠减重饮食加最大耐受剂量的乙酰唑胺（最高4 g/d）或安慰剂，为期6个月。

主要观察指标

不良事件（AE），研究访视时的临床和实验室检查结果评估。

结果

随机分配到乙酰唑胺组的86名参与者中，有38名（44.1%）耐受了4 g/d的最大允许剂量。乙酰唑胺组达到最大研究剂量的平均时间为13周（中位数12周；范围10 - 24周）。共报告了676例不良事件（乙酰唑胺组，n = 480；安慰剂组，n = 196）和9例严重不良事件（乙酰唑胺组，n = 6；安慰剂组，n = 3）。值得注意的是，乙酰唑胺组中报告至少1例神经、胃肠、代谢和肾脏器官系统不良事件的参与者百分比显著更高（P < 0.05）。乙酰唑胺组感觉异常（OR 9.82；95% CI 3.87 - 27.82）、味觉障碍（OR ∞；95% CI 3.99 - ∞）、呕吐和腹泻（OR 4.11；95% CI 1.04 - 23.41）、恶心（OR 2.99；95% CI 1.26 - 7.49）和疲劳（OR 16.48；95% CI 2.39 - 702.40）的发生率高于安慰剂组。