Preoperative Alpha Blockade for Pheochromocytoma

Pheochromocytoma Clinical Trial

Official title:

Randomized Controlled Trial of Preoperative Alpha Blockade for Pheochromocytoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03176693
• Other study ID #: IRB#17-000048
• Status: Completed
• Phase: Phase 3
• Start date: May 5, 2017
• Est. completion date: October 10, 2021

Study information

• Verified date: November 2023
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Pheochromocytoma is a rare, catecholamine (ex. adrenaline) secreting tumor that requires preoperative alpha blockade to minimize intraoperative hemodynamic instability, thereby reducing intra- and postoperative morbidity and mortality. Phenoxybenzamine is a non-selective alpha blocker that is significantly more expensive and is associated with increased adverse effects in comparison with selective alpha blockers such as doxazosin. Retrospective studies show minimal differences in hemodynamic instability and no differences in postoperative morbidity and mortality between selective vs. non-selective alpha blockers. This study is a randomized controlled trial that will compare hemodynamic instability, morbidity, mortality, cost, and quality of life between patients blocked with phenoxybenzamine vs. doxazosin.

Description:

Pheochromocytoma is a catecholamine (ex. adrenaline) secreting tumor for which the primary treatment is surgical resection. Due to the hormones secreted by the tumor, alpha receptors on peripheral blood vessels are activated, causing constriction of these blood vessels and dangerously high blood pressure. During resection of the tumor, the source of excess hormone secretion is abruptly removed, which can lead to life-threatening blood pressure fluctuations during surgery.

Alpha blockers are a class of medication that blocks the alpha receptor on blood vessels. Given preoperatively over a few weeks, these medications negate the effects of the excess hormones secreted by the pheochromocytoma, reducing the frequency and severity of dangerous blood pressure fluctuations intraoperatively and postoperatively. Preoperative alpha blockade is therefore critical to safely perform surgery to resect pheochromocytoma.

Phenoxybenzamine, a non-selective alpha blocker, is the most common medication used to alpha block patients prior to pheochromocytoma resection. However, due to increasing drug costs and increased side effects in comparison with selective alpha blockers, there is a renewed interest in studying alternatives to phenoxybenzamine.

Selective alpha blockers such as doxazosin are also commonly used to alpha block patients prior to pheochromocytoma resection. Selective alpha blockers are significantly less expensive and are associated with fewer side effects than phenoxybenzamine. Most retrospective studies comparing phenoxybenzamine with selective alpha blockers show no difference in intraoperative blood pressure fluctuations, morbidity, or mortality in pheochromocytoma resection. However, no prospective, randomized controlled trials comparing phenoxybenzamine to selective alpha blockers have been performed.

The purpose of our study is to analyze preoperative, intraoperative, and postoperative outcomes in patients randomized to receive phenoxybenzamine (non-selective) or doxazosin (selective) for alpha blockade prior to pheochromocytoma resection. Outcomes will include postoperative morbidity and mortality, intraoperative hemodynamic instability, quality of life, and cost.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: October 10, 2021
• Est. primary completion date: January 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adults with pheochromocytoma / paraganglioma undergoing surgical resection

Exclusion Criteria:

• Children < 18 years

Related Conditions & MeSH terms

• Paraganglioma
• Pheochromocytoma

Intervention

Drug:
• Phenoxybenzamine
Non-selective alpha blocker
• Doxazosin
Selective alpha blocker

Locations

Country	Name	City	State
United States	University of California, Los angeles	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Los Angeles

Country where clinical trial is conducted

United States, 

References & Publications (7)

Brunaud L, Boutami M, Nguyen-Thi PL, Finnerty B, Germain A, Weryha G, Fahey TJ 3rd, Mirallie E, Bresler L, Zarnegar R. Both preoperative alpha and calcium channel blockade impact intraoperative hemodynamic stability similarly in the management of pheochro — View Citation

Kesselheim AS, Avorn J, Sarpatwari A. The High Cost of Prescription Drugs in the United States: Origins and Prospects for Reform. JAMA. 2016 Aug 23-30;316(8):858-71. doi: 10.1001/jama.2016.11237. — View Citation

Kiernan CM, Du L, Chen X, Broome JT, Shi C, Peters MF, Solorzano CC. Predictors of hemodynamic instability during surgery for pheochromocytoma. Ann Surg Oncol. 2014 Nov;21(12):3865-71. doi: 10.1245/s10434-014-3847-7. Epub 2014 Jun 18. — View Citation

Livingstone M, Duttchen K, Thompson J, Sunderani Z, Hawboldt G, Sarah Rose M, Pasieka J. Hemodynamic Stability During Pheochromocytoma Resection: Lessons Learned Over the Last Two Decades. Ann Surg Oncol. 2015 Dec;22(13):4175-80. doi: 10.1245/s10434-015-4519-y. Epub 2015 Mar 31. — View Citation

Prys-Roberts C, Farndon JR. Efficacy and safety of doxazosin for perioperative management of patients with pheochromocytoma. World J Surg. 2002 Aug;26(8):1037-42. doi: 10.1007/s00268-002-6667-z. Epub 2002 Jun 19. — View Citation

Randle RW, Balentine CJ, Pitt SC, Schneider DF, Sippel RS. Selective Versus Non-selective alpha-Blockade Prior to Laparoscopic Adrenalectomy for Pheochromocytoma. Ann Surg Oncol. 2017 Jan;24(1):244-250. doi: 10.1245/s10434-016-5514-7. Epub 2016 Aug 25. — View Citation

Weingarten TN, Cata JP, O'Hara JF, Prybilla DJ, Pike TL, Thompson GB, Grant CS, Warner DO, Bravo E, Sprung J. Comparison of two preoperative medical management strategies for laparoscopic resection of pheochromocytoma. Urology. 2010 Aug;76(2):508.e6-11. d — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hemodynamic Instability	Proportion of operative time outside target thresholds: SBP >180 or <80; DBP > 90; MAP>150 or <50; HR>90.; Arterial line blood pressure measurements were extracted from the electronic medical record every 60 seconds.	Intraoperative, approximately 90 minutes
Secondary	Mortality	Death within 30 days of surgery	30 days postoperatively
Secondary	Daily Cost of Drug		Preoperative (2-3 weeks prior to surgery)
Secondary	Quality of Life- Physical Functioning, Role Limitations Due to Physical Problems, Bodily Pain, General Health Perceptions, Vitality, Social Functioning, Role-limitations Due to Emotional Problems, and Mental Health	Patients will take the SF-36 as well as a symptom survey describing the frequency and impact on their quality of life at several time points including prior to starting alpha blockade, immediately prior to surgery after being sufficiently blocked, and postoperatively at 30 days, 3 months, 6 months, and 1 year	From date of surgery (-2 to 3 weeks, -1 day, 30 days, 3 months, 6 months, 1 year)
Secondary	Morbidity as Assessed by Occurrence of Adverse Events	Morbidity will be graded by Clavien Classification of adverse events	Postoperatively during inpatient stay and during readmissions up to 30 days postoperatively
Secondary	Participants Admitted to Post-operative Intensive Care Unit (ICU)		up to 30 days post-surgery