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.

Start Date18 Jan 2023

Sponsor / Collaborator

Seoul National University Hospital

NCT01379898 / CompletedPhase 4IIT

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.

Start Date01 Dec 2011

Sponsor / Collaborator

University Medical Center Groningen

[+13]

CTRI/2011/09/002019 / RecruitingPhase 4

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

Start Date27 Sep 2011

Sponsor / Collaborator

Sanjay Gandhi Post Graduate Institute of Medical Sciences

100 Clinical Results associated with Phenoxybenzamine Hydrochloride

100 Translational Medicine associated with Phenoxybenzamine Hydrochloride

100 Patents (Medical) associated with Phenoxybenzamine Hydrochloride

5,120

Literatures (Medical) associated with Phenoxybenzamine Hydrochloride

01 Dec 2023·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

Author: Amsellem, Pierre ; Selmic, Laura E ; Traverson, Marine ; Piegols, Hunter J ; Souza, Carlos H ; Cray, Megan T ; Williams, Elroy ; Murphy, Christina ; Liptak, Julius M ; 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.

23 Oct 2023·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

Author: Li, Youxin ; Nan, Yaqin ; 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.

01 Oct 2023·Journal of surgical oncology

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

Article

Author: 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.

100 Deals associated with Phenoxybenzamine Hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
D00507	Phenoxybenzamine Hydrochloride	C04AX02	DB00925

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Peripheral Vasospasm	CN	Suzhou Homesun Pharmaceutical Co. Ltd.	01 Jan 1987
Urinary Retention	CN	Suzhou Homesun Pharmaceutical Co. Ltd.	01 Jan 1987
Hypertension	US	Concordia Pharmaceuticals, Inc.	26 Jan 1953
Pheochromocytoma	US	Concordia Pharmaceuticals, Inc.	26 Jan 1953

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00620945 (CTgov)	Not Applicable	Heart Defects, Congenital	87	Phenoxybenzamine (Phenoxybenzamine Treatment)	qokhgisyhc(sldghsynkh) = jynxhlqksd lkmwfblgvc (puummkibtw, odfejrpzhv - ianrtzegvt) View more	-	20 Nov 2017
NCT00620945 (CTgov)	Not Applicable	Heart Defects, Congenital	87	Phenoxybenzamine (Phenoxybenzamine)	qhuhautdgq(vxjokrejny) = ofwzkmlovy ymjfkisplp (ezmbmzrqog, gkshzxceqt - yfwzuojbzh) View more	-	20 Nov 2017
NCT00569855 (CTgov)	Phase 2	Heart Diseases	785	phenoxybenzamine	cjkupfhlxu(doxpvcmrlk) = mfgtrpfbsg sxhrrztbxd (vlwcvkvphk, vsaxjjoxzh - ghyfqtlqzp) View more	-	01 Mar 2011

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