Preoperative Alpha Blockade for Pheochromocytoma

NCT03176693 | Completed Phase 3 Results FDA Drug

• 1 other identifier: IRB#17-000048
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pheochromocytoma; Paraganglioma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Mortality

  30 days postoperatively

• Daily Cost of Drug

  Preoperative (2-3 weeks prior to surgery)

• 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

  From date of surgery (-2 to 3 weeks, -1 day, 30 days, 3 months, 6 months, 1 year)

• Morbidity as Assessed by Occurrence of Adverse Events

  Postoperatively during inpatient stay and during readmissions up to 30 days postoperatively

• Participants Admitted to Post-operative Intensive Care Unit (ICU)

  up to 30 days post-surgery

Study Arms (2)

Phenoxybenzamine

ACTIVE COMPARATOR

3-4 weeks prior to date of surgery, patient will start phenoxybenzamine 10mg PO twice daily. Phenoxybenzamine will then be titrated to a blood pressure \<120/80 (sitting) with mild orthostatic hypotension (drop in systolic blood pressure by 20 points or diastolic blood pressure by 10 points from sitting to standing position); systolic blood pressure not less than 90 (standing).

Drug: Phenoxybenzamine

Doxazosin

EXPERIMENTAL

3-4 weeks prior to date of surgery, patient will start doxazosin 1 mg PO daily. Phenoxybenzamine will then be titrated to a blood pressure \<120/80 (sitting) with mild orthostatic hypotension (drop in systolic blood pressure by 20 points or diastolic blood pressure by 10 points from sitting to standing position); systolic blood pressure not less than 90 (standing).

Drug: Doxazosin

Interventions

Phenoxybenzamine DRUG

Non-selective alpha blocker

Also known as: Dibenzyline

Phenoxybenzamine

Doxazosin DRUG

Selective alpha blocker

Also known as: Cardura

Doxazosin

Eligibility Criteria

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

You may qualify if:

• Adults with pheochromocytoma / paraganglioma undergoing surgical resection

You may not qualify if:

• Children \< 18 years

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

University of California, Los angeles

Los Angeles, California, 90025, United States

Location

Related Publications (7)

• 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.

  PMID: 25822781 BACKGROUND

• 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.

  PMID: 27552619 BACKGROUND

• 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.

  PMID: 27561909 RESULT

• 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.

  PMID: 24939623 RESULT

• 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 pheochromocytoma. Surgery. 2014 Dec;156(6):1410-7; discussion1417-8. doi: 10.1016/j.surg.2014.08.022. Epub 2014 Nov 11.

  PMID: 25456922 RESULT

• 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. doi: 10.1016/j.urology.2010.03.032. Epub 2010 May 23.

  PMID: 20546874 RESULT

• 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.

  PMID: 12192533 RESULT

MeSH Terms

Conditions

Pheochromocytoma; Paraganglioma

Interventions

Phenoxybenzamine; Doxazosin

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; Prazosin; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Masha Livhits, MD
• Organization: University of California Los Angeles

mlivhits@mednet.ucla.edu

310-206-0585

Study Officials

• Michael Yeh, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Co-Principal Investigator

Study Record Dates

• First Submitted: May 31, 2017
• First Posted: June 5, 2017
• Study Start: May 5, 2017
• Primary Completion: January 31, 2020
• Study Completion: October 10, 2021
• Last Updated: November 20, 2023
• Results First Posted: November 20, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)