The Effect and Safety of Omitting Preoperative Alpha-adrenergic Blockade for Normotensive Pheochromocytoma

NCT05702944 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 2209-044-1357
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pheochromocytoma; Paraganglioma; Adrenalectomy; Status; Adrenergics Causing Adverse Effects in Therapeutic Use

Outcome Measures

Primary Outcomes (1)

• The effect and safety of omitting preoperative alpha blockade during surgery

  Percentage of time during the surgery with systolic blood pressure \> 160mmHg or average blood pressure \< 60mmHg

  during surgery

Secondary Outcomes (3)

• The effect and safety of omitting preoperative alpha blockade during surgery

  during surgery

• The effect and safety of omitting preoperative alpha blockade before surgery

  3 days, 2 days, 1 day before surgery

• The effect and safety of omitting preoperative alpha blockade after surgery

  1 day, 2 day, 2 weeks, 3 months after surgery

Study Arms (2)

Phenoxybenzamine before surgery

SHAM COMPARATOR

Phenoxybenzamine, an alpha receptor blocker, is taken at least 2 to 5 weeks before surgery

Drug: Phenoxybenzamine

No phenoxybenzamine before surgery

ACTIVE COMPARATOR

Phenoxybenzamine, an alpha receptor blocker, is not taken before surgery

Drug: Phenoxybenzamine

Interventions

Phenoxybenzamine DRUG

Patients in sham comparator group take a phenoxybenzamine at least 2 to 5 weeks before surgery. If blood pressure is more than 130/80 mmHg in the sitting position, the patient will take a more amount of phenoxybenzamine. If blood pressure is less than 90 mmHg in the standing position, the patient will take a less amount of phenoxybenzamine. In active comparator group, there is no drug to be taken.

No phenoxybenzamine before surgery; Phenoxybenzamine before surgery

Eligibility Criteria

• Age: 19 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 19 to 70 years old
• Patients who consented to the study and obtained consent for the study
• Patients undergoing unilateral total adrenalectomy due to normotensive pheochromocytoma/paraganglioma with less than five times of upper limits of serum metanephrine

You may not qualify if:

• Patients under 18 or over 70 years old
• Pregnant women
• Patients with bilateral pheochromocytoma
• Patients suspected of malignant pheochromocytoma/paraganglioma or distant metastasis
• Patients requiring preoperative intensive care unit due to severe hemodynamic instability
• Patients with hypertension (the blood pressure measured more than two times is constantly greater than 140/90 mmHg) or already taking a antihypertensive medication
• Patients with a history of coronary artery disease
• Patients with a history of arrhythmia (atrial fibrillation, Paroxysmal supraventricular tachycardia)
• Patients with a history of cerebrovascular disease (cerebral aneurysm, cerebral infarction, cerebral hemorrhage)
• Patients judged unsuitable by the person in charge of the clinical trial

Sponsors & Collaborators

• Seoul National University Hospital: lead

Study Sites (1)

Seoul National University Hospital

Seoul, South Korea

RECRUITING

Related Publications (15)

• Stenstrom G, Svardsudd K. Pheochromocytoma in Sweden 1958-1981. An analysis of the National Cancer Registry Data. Acta Med Scand. 1986;220(3):225-32.

  PMID: 3776697 BACKGROUND

• Sheps SG, Jiang NS, Klee GG. Diagnostic evaluation of pheochromocytoma. Endocrinol Metab Clin North Am. 1988 Jun;17(2):397-414.

  PMID: 3042392 BACKGROUND

• Samaan NA, Hickey RC, Shutts PE. Diagnosis, localization, and management of pheochromocytoma. Pitfalls and follow-up in 41 patients. Cancer. 1988 Dec 1;62(11):2451-60. doi: 10.1002/1097-0142(19881201)62:113.0.co;2-q.

  PMID: 3179962 BACKGROUND

• Lenders JW, Duh QY, Eisenhofer G, Gimenez-Roqueplo AP, Grebe SK, Murad MH, Naruse M, Pacak K, Young WF Jr; Endocrine Society. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014 Jun;99(6):1915-42. doi: 10.1210/jc.2014-1498.

  PMID: 24893135 BACKGROUND

• Lenders JW, Eisenhofer G, Mannelli M, Pacak K. Phaeochromocytoma. Lancet. 2005 Aug 20-26;366(9486):665-75. doi: 10.1016/S0140-6736(05)67139-5.

  PMID: 16112304 BACKGROUND

• Pacak K. Preoperative management of the pheochromocytoma patient. J Clin Endocrinol Metab. 2007 Nov;92(11):4069-79. doi: 10.1210/jc.2007-1720.

  PMID: 17989126 BACKGROUND

• Chen H, Sippel RS, O'Dorisio MS, Vinik AI, Lloyd RV, Pacak K; North American Neuroendocrine Tumor Society (NANETS). The North American Neuroendocrine Tumor Society consensus guideline for the diagnosis and management of neuroendocrine tumors: pheochromocytoma, paraganglioma, and medullary thyroid cancer. Pancreas. 2010 Aug;39(6):775-83. doi: 10.1097/MPA.0b013e3181ebb4f0.

  PMID: 20664475 BACKGROUND

• Haissaguerre M, Courel M, Caron P, Denost S, Dubessy C, Gosse P, Appavoupoulle V, Belleannee G, Jullie ML, Montero-Hadjadje M, Yon L, Corcuff JB, Fagour C, Mazerolles C, Wagner T, Nunes ML, Anouar Y, Tabarin A. Normotensive incidentally discovered pheochromocytomas display specific biochemical, cellular, and molecular characteristics. J Clin Endocrinol Metab. 2013 Nov;98(11):4346-54. doi: 10.1210/jc.2013-1844. Epub 2013 Sep 3.

  PMID: 24001749 BACKGROUND

• Kopetschke R, Slisko M, Kilisli A, Tuschy U, Wallaschofski H, Fassnacht M, Ventz M, Beuschlein F, Reincke M, Reisch N, Quinkler M. Frequent incidental discovery of phaeochromocytoma: data from a German cohort of 201 phaeochromocytoma. Eur J Endocrinol. 2009 Aug;161(2):355-61. doi: 10.1530/EJE-09-0384. Epub 2009 Jun 4.

  PMID: 19497985 BACKGROUND

• Noshiro T, Shimizu K, Watanabe T, Akama H, Shibukawa S, Miura W, Ito S, Miura Y. Changes in clinical features and long-term prognosis in patients with pheochromocytoma. Am J Hypertens. 2000 Jan;13(1 Pt 1):35-43. doi: 10.1016/s0895-7061(99)00139-9.

  PMID: 10678269 BACKGROUND

• Bruynzeel H, Feelders RA, Groenland TH, van den Meiracker AH, van Eijck CH, Lange JF, de Herder WW, Kazemier G. Risk Factors for Hemodynamic Instability during Surgery for Pheochromocytoma. J Clin Endocrinol Metab. 2010 Feb;95(2):678-85. doi: 10.1210/jc.2009-1051. Epub 2009 Dec 4.

  PMID: 19965926 BACKGROUND

• Shao Y, Chen R, Shen ZJ, Teng Y, Huang P, Rui WB, Xie X, Zhou WL. Preoperative alpha blockade for normotensive pheochromocytoma: is it necessary? J Hypertens. 2011 Dec;29(12):2429-32. doi: 10.1097/HJH.0b013e32834d24d9.

  PMID: 22025238 BACKGROUND

• Lafont M, Fagour C, Haissaguerre M, Darancette G, Wagner T, Corcuff JB, Tabarin A. Per-operative hemodynamic instability in normotensive patients with incidentally discovered pheochromocytomas. J Clin Endocrinol Metab. 2015 Feb;100(2):417-21. doi: 10.1210/jc.2014-2998. Epub 2014 Nov 18.

  PMID: 25405501 BACKGROUND

• Buitenwerf E, Osinga TE, Timmers HJLM, Lenders JWM, Feelders RA, Eekhoff EMW, Haak HR, Corssmit EPM, Bisschop PHLT, Valk GD, Veldman RG, Dullaart RPF, Links TP, Voogd MF, Wietasch GJKG, Kerstens MN. Efficacy of alpha-Blockers on Hemodynamic Control during Pheochromocytoma Resection: A Randomized Controlled Trial. J Clin Endocrinol Metab. 2020 Jul 1;105(7):2381-91. doi: 10.1210/clinem/dgz188.

  PMID: 31714582 BACKGROUND

• Kim JH, Lee HC, Kim SJ, Lee KE, Jung KC. Characteristics of Intraoperative Hemodynamic Instability in Postoperatively Diagnosed Pheochromocytoma and Sympathetic Paraganglioma Patients. Front Endocrinol (Lausanne). 2022 Feb 24;13:816833. doi: 10.3389/fendo.2022.816833. eCollection 2022.

  PMID: 35282440 BACKGROUND

MeSH Terms

Conditions

Pheochromocytoma; Paraganglioma

Interventions

Phenoxybenzamine

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Ethylamines; Amines; Organic Chemicals

Study Officials

• Su-Jin Kim, M.D., Ph.D

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Su-Jin Kim, M.D., Ph.D.

CONTACT

+82-2-2072-7208; su.jin.kim.md@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Patients in control group take a "phenoxybenzamine" at least 2 to 5 weeks before surgery. If blood pressure is more than 130/80 mmHg in the sitting position, the patient will take a more amount of "phenoxybenzamine". If blood pressure is less than 90 mmHg in the standing position, the patient will take a less amount of "phenoxybenzamine". In the case group, there is no drug to be taken.

Study Record Dates

• First Submitted: November 10, 2022
• First Posted: January 27, 2023
• Study Start: January 18, 2023
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: June 12, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)