A Pilot Study for Randomized Controlled Trial on the Effect and Safety of Omitting Preoperative Alpha-adrenergic Blockade for Normotensive Pheochromocytoma

Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors originating from catecholamine producing chromaffin cells in the adrenal medulla and extra-adrenal paraganglia. The overall age-standardized incidence rate is 0.18 per 100,000 person-years in Korea.
The definitive treatment of PPGL is surgical excision of tumor. However, surgery is associated with a high risk of perioperative hemodynamic instability (HI). To avoid perioperative HI in patients diagnosed with PPGL, preoperative management including routine use of alpha blockade and volume expansion has been advocated by several guidelines.
While unstable hypertension and tachycardia should be controlled in patients with PPGL, there is controversial that all patients diagnosed with PPGL should undergo preoperative pharmacological treatment, especially alpha blockade. The most important risk of preoperative alpha blockade use is perioperative hypotension.
A recent study reported that patients diagnosed with PPGL postoperatively may have no further higher risk of intraoperative hypertension than those diagnosed preoperatively despite insufficient preoperatively management of PPGL.
Therefore, it is a very important to study the relationship between HI and preoperative alpha blockade in normotensive patients diagnosed with PPGL. The aim this study is to analyze the effect and safety of omitting preoperative alpha-adrenergic blockade for normotensive pheochromocytoma through a prospective randomized controlled trial. The patients is divided into two groups. The patients in control group take a phenoxybenzamine at least 2 to 5 weeks before surgery. The patients in case group do not take a phenoxybenzamine.
Primary outcome is to evaluate the percentage of time during surgery with systolic blood pressure more than 160mmHg or average blood pressure less than 60mmHg. And secondary outcomes are to evaluate hemodynamic instability in preoperative ward and postoperative ward.

开始日期2023-01-18

申办/合作机构

Seoul National University Hospital

NCT01379898 / Completed临床4期IIT

Pheochromocytoma Randomised Study Comparing Adrenoreceptor Inhibiting Agents for Preoperative Treatment

Rationale: The optimal preoperative medical management for patients with a pheochromocytoma is currently unknown. In particular, there is no agreement with respect to whether phenoxybenzamine or doxazosin is the optimal alfa-adrenoreceptor antagonist to be administered before surgical resection of a pheochromocytoma. We hypothesized that the competitive alfa1-antagonist doxazosin is superior to the non-competitive alfa1- and alfa2-antagonist phenoxybenzamine.
Objective: comparing effects of preoperative treatment with either phenoxybenzamine or doxazosin on intraoperative hemodynamic control in patients undergoing surgical resection of a pheochromocytoma.
Study design: Randomised controlled open-label trial.
Study population: 18 - 55 yr old. Adult patients with a recently diagnosed benign pheochromocytoma.
Intervention: Patients are randomised to receive oral treatment with either phenoxybenzamine or doxazosin preoperatively.
Main study parameters/endpoints: The main study parameter is defined as the percentage of intraoperative time that blood pressure is outside the predefined target range after pretreatment with either phenoxybenzamine or doxazosin.
In this multicenter trial, we compare the effects of two commonly used drugs in patients being medically prepared for resection of a benign pheochromocytoma. Participants are not subjected to an experimental treatment of any kind, as we merely aim to describe in detail the perioperative course in general and, in particular, the intraoperative hemodynamic control in patients treated preoperatively with either phenoxybenzamine or doxazosin. A routine diagnostic work-up for pheochromocytoma will be performed in all participants. One extra blood sample (volume: 48,5 mL) is drawn before start of the study medication, and participants need to record their symptoms in a diary. In addition, patients who are pretreated in the outpatient clinic monitor their blood pressure and pulse rate at home with an automated device. Treatment with an alfa-adrenoreceptor antagonist is initiated at least 2 - 3 weeks prior to surgery. Patients who are admitted to the hospital for pretreatment with an alfa-adrenoreceptor antagonist have their blood pressure and pulse rate measured by the nursing staff. The final site visit is planned at 30 days after surgery, in line with current practice.

开始日期2011-12-01

申办/合作机构

University Medical Center Groningen

[+13]

CTRI/2011/09/002019 / Recruiting临床4期

Comparative study of pre-operative blockade using Phenoxybenzamine vs. Prazosin efficacy ( intra- and post-operative hemodynamic changes) and safety profile in Pheochromocytoma

开始日期2011-09-27

申办/合作机构

Sanjay Gandhi Post Graduate Institute of Medical Sciences

100 项与盐酸酚苄明相关的临床结果

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100 项与盐酸酚苄明相关的转化医学

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100 项与盐酸酚苄明相关的专利（医药）

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5,131

项与盐酸酚苄明相关的文献（医药）

2023-12-01·Veterinary and comparative oncology

Risk factors influencing death prior to discharge in 302 dogs undergoing unilateral adrenalectomy for treatment of primary adrenal gland tumours

Article

作者: Amsellem, Pierre ; Selmic, Laura E ; Traverson, Marine ; Souza, Carlos H ; Piegols, Hunter J ; Cray, Megan T ; Williams, Elroy ; Liptak, Julius M ; Murphy, Christina ; Skinner, Owen T ; Dornbusch, Josephine A ; Wustefeld-Janssens, Brandan G ; Stephens, Julie A ; Lapsley, Janis M ; Abrams, Brittany E

Abstract:

Adrenalectomies for canine adrenal tumours are associated with peri‐operative morbidity and mortality. Objectives of this study included assessing the prognostic value of tumour‐ or surgery‐related variables in predicting peri‐operative mortality and overall survival in dogs undergoing adrenalectomies for primary adrenal tumours as well as pre‐treatment with phenoxybenzamine on survival to discharge with pheochromocytomas specifically. A multi‐institutional retrospective cohort study was performed across nine institutions. Electronic medical record searches identified 302 dogs which met the inclusion criteria. Data collected included dog‐related, tumour‐related, treatment‐related, surgery‐related, and outcome variables. Univariate and multivariable logistic regression and cox proportional hazards models were used to identify variables associated with death prior to discharge and tumour‐related survival. Overall, 87% of dogs survived to discharge with a tumour‐related survival time of 3.96 years. Post‐operative complications were reported in 25%. Increased surgical time (p = 0.002) and pre‐surgical medical treatment other than phenoxybenzamine (p = 0.024) were significantly associated with increased peri‐operative mortality while ureteronephrectomy (p = 0.021), post‐operative pancreatitis (p = 0.025), and post‐operative aspiration pneumonia (p < 0.001) were significantly associated with decreased overall survival. Phenoxybenzamine pretreatment had no effect on peri‐operative mortality. Thirty‐seven of 45 (82%) dogs with pheochromocytomas not pretreated survived to discharge, and 50 of 59 (85%) dogs with pheochromocytomas pretreated with phenoxybenzamine survived to discharge (p = 0.730). This study provides information on risk factors for death prior to discharge and tumour‐related survival that may help guide clinical management and owner expectations. In addition, the study findings challenge the previously reported benefit of phenoxybenzamine for pretreatment of dogs undergoing adrenalectomies for pheochromocytomas.

2023-10-23·Analytica chimica acta

Enhancement of chiral drugs separation by a novel adjustable gravity mediated capillary electrophoresis combined with sulfonic propyl ether β-CD polymer.

Article

作者: Nan, Yaqin ; Li, Youxin ; Cheng, Mengqi ; Liang, Qinggang ; Zhao, Ran ; Jia, Haijiao ; Bao, James J ; Zheng, Pingyi

A water-soluble negative sulfonic propyl ether β-CD polymer (SPE-β-CDP) to be used as chiral selector in capillary electrophoresis (CE) was polymerized. The sulfonic substitution degree of each β-CD in SPE-β-CDP was statistically homogenized. The only one negative peak in electrophoretogram with indirect ultraviolate method proved its uniformity of electrophoretic behavior. There were 7.12 sulfonic substitution in β-CD unit and 164 μmole β-CD units in each gram of SPE-β-CDP, which corresponded a molecular weight of 7000 or more. Compared with monomer, SPE-β-CDP was lower effect on electrical current of CE, indicating a high concentration of SPE-β-CDP could be added. Its separation ability was verified by 12 chiral drugs. SPE-β-CDP also showed advantages of good water solubility, easy preparation and recovery to reduce the overall cost. However, five of 12 chiral drugs were hardly to be fully separated which was normal for any kind of chiral selector. A newly adjustable gravity mediated capillary electrophoresis (AGM-CE) technology was proposed and combined with SPE-β-CDP to enhance the chiral separation efficiencies of propranolol, salbutamol, omeprazole, ofloxacin and phenoxybenzamine which were markedly improved to 3.02, 1.17, 7.63, 4.14, and 2.81, respectively. Furthermore, its gradient mode (AGMg-CE) was also used to improve resolution through utilizing the zero mobility point, at which the effective apparent mobility of one racemate was zero. Resolutions of five chiral drugs were significantly improved, especially resolution of carvedilol changed from 0.43 to 1.0. These indicated SPE-β-CDP as chiral selector, AGM-CE and AGMg-CE as new CE technologies had a great potential in chiral separation.

2023-10-01·Journal of surgical oncology

Reduced uptake pattern on ⁶⁸ Ga-DOTATATE-scan may indicate necrosis predicting aggressive behavior in pheochromocytoma and paragangliomas (PPGLs).

Article

作者: Parameswaran, Rajeev ; Pinto, Diluka ; de Jong, Mechteld Christine

BACKGROUND:

Predicting malignancy among pheochromocytoma paragangliomas (PPGLs) remains a challenge, with only limited understanding of the clinical and molecular characteristics. It has been suggested that reduced avidity of a PPGL on ⁶⁸ Ga-DOTATATE PET/CT could be a sign of not only altered metabolic activity, but also of increased biologic aggressiveness, possibly due to loss of SSTR-expression.

DESIGN:

Retrospective cohort review.

PATIENTS AND MEASUREMENTS:

Thirty-seven patients who underwent treatment for PPGL at a tertiary institution over the period 2010-2022, had their biochemical, radiological, and clinicopathological variables collected.

RESULTS:

Five of 37 (13%) patients (5 males) with a mean age of 42 years were found to have malignant PPGLs. The mean size of the tumors were 5.4 cm, with 4 located in the paraaortic area and 1 in right adrenal. Functional imaging with ⁶⁸ Ga-DOTATATE PET/CT showed a mean SUV_max of 4.5. Four of 5 patients underwent open resection of the tumors under general anesthesia following preoperative alpha blockade with oral phenoxybenzamine. The mean PASS score of the excised tumors was 5.5 in keeping with biologically aggressive tumors, with evidence of necrosis. All but 1 patient had germline SDHB-mutation (Deletion Exon 1). Postintervention after a mean follow-up of 31 months, 2 of 5 (40%) patient developed spinal metastasis and 1 patients (25%) died of cardiac complications.

CONCLUSION:

A non-highly avid PPGL on DOTATE scan should be considered as possibly having necrosis of tumors indicating a more aggressive tumor-biology. There might be a subgroup of patients in whom FDG-PET scan should be considered to gain additional information.

项与盐酸酚苄明相关的新闻（医药）

2022-12-13

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【瞩目】科伦发威！进攻10亿大品种

精彩内容12月12日，CDE官网显示，科伦药业以仿制4类报产的盐酸乌拉地尔注射液获得承办受理。盐酸乌拉地尔注射液为静脉降压药，2021年在中国公立医疗机构终端销售额突破10亿元。乌拉地尔是一种选择性α1受体阻滞剂，具有外周和中枢双重降压作用。盐酸乌拉地尔注射液主要适用于高血压危象以及控制围手术期高血压，在临床上应用甚广，是急诊室常备急救药品之一。米内网数据显示，2021年中国城市公立医院、县级公立医院、城市社区中心以及乡镇卫生院（简称中国公立医疗机构）终端乌拉地尔注射剂销售规模接近15亿元，同比增长14.64%。其中，盐酸乌拉地尔注射液销售额首次突破10亿元，同比增长18.61%。中国公立医疗机构终端盐酸乌拉地尔注射液销售情况（单位：万元）来源：米内网中国公立医疗机构药品终端竞争格局目前，国内已上市的乌拉地尔制剂包括盐酸乌拉地尔注射液、注射用盐酸乌拉地尔、乌拉地尔注射液、乌拉地尔缓释片、乌拉地尔缓释胶囊、乌拉地尔葡萄糖注射液、乌拉地尔氯化钠注射液。科伦药业获批上市的高血压用药来源：米内网新版数据库在高血压用药领域，科伦药业累计已有10个品种获批上市，包括阿替洛尔片、注射用呋塞米、盐酸酚苄明片、注射用硝普钠、盐酸拉贝洛尔片、替米沙坦片、替米沙坦胶囊、尼群地平片、尼莫地平片、尼莫地平注射液。数据来源：米内网数据库、CDE注：米内网《中国公立医疗机构药品终端竞争格局》，统计范围是：中国城市公立医院、县级公立医院、城市社区中心以及乡镇卫生院，不含民营医院、私人诊所、村卫生室；上述销售额以产品在终端的平均零售价计算。本文为原创稿件，转载请注明来源和作者，否则将追究侵权责任。投稿及报料请发邮件到872470254@qq.com稿件要求详询米内微信首页菜单栏商务及内容合作可联系QQ：412539092【分享、点赞、在看】点一点不失联哦

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100 项与盐酸酚苄明相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00507	盐酸酚苄明	C04AX02	DB00925

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
外周血管痉挛性疾病	中国	苏州弘森药业股份有限公司	1987-01-01
尿潴留	中国	苏州弘森药业股份有限公司	1987-01-01
高血压	美国	Concordia Pharmaceuticals, Inc.	1953-01-26
嗜铬细胞瘤	美国	Concordia Pharmaceuticals, Inc.	1953-01-26

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00620945 (CTgov)	N/A	先天性心脏缺损	87	Phenoxybenzamine (Phenoxybenzamine Treatment)	簾夢簾艱構鹹醖鹹襯艱(艱襯壓遞窪憲觸構膚廠) = 鏇構築餘鬱鹹範觸範衊廠範鹹廠積網餘鹽夢積 (蓋願夢艱蓋糧餘積膚夢, 遞獵窪淵鹹糧壓築選膚 ~ 艱築膚憲餘範遞鏇鏇襯) 更多	-	2017-11-20
NCT00620945 (CTgov)	N/A	先天性心脏缺损	87	Phenoxybenzamine (Phenoxybenzamine)	壓廠鹽壓鹹繭鏇壓製餘(鹹鏇膚鏇顧遞窪艱壓鬱) = 餘鹽範廠膚鏇窪廠夢壓簾鬱廠憲網壓衊範壓餘 (構製築齋構鹽築顧壓簾, 衊淵憲蓋淵夢膚積願獵 ~ 壓糧選艱夢範窪顧鹽淵) 更多	-	2017-11-20
NCT00569855 (CTgov)	临床2期	心脏病	785	phenoxybenzamine	鬱簾夢觸夢遞廠網餘襯(積積積憲夢願鑰獵鑰醖) = 構願糧願獵鹽憲齋窪衊廠繭鏇範製構鏇築齋糧 (繭夢襯願窪廠衊觸遞製, 築醖艱構襯簾衊構夢遞 ~ 繭繭觸鑰醖餘鬱鏇鑰憲) 更多	-	2011-03-01