Preoperative Alpha Blockade for Pheochromocytoma

November 2, 2023 updated by: Masha Livhits, University of California, Los Angeles

Randomized Controlled Trial of Preoperative Alpha Blockade for Pheochromocytoma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

39

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90025
        • University of California, Los Angeles

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adults with pheochromocytoma / paraganglioma undergoing surgical resection

Exclusion Criteria:

  • Children < 18 years

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Phenoxybenzamine
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
Non-selective alpha blocker
Other Names:
  • Dibenzyline
Experimental: Doxazosin
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
Selective alpha blocker
Other Names:
  • Cardura

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hemodynamic Instability
Time Frame: Intraoperative, approximately 90 minutes

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: 30 days postoperatively
Death within 30 days of surgery
30 days postoperatively
Daily Cost of Drug
Time Frame: Preoperative (2-3 weeks prior to surgery)
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
Time Frame: From date of surgery (-2 to 3 weeks, -1 day, 30 days, 3 months, 6 months, 1 year)
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)
Morbidity as Assessed by Occurrence of Adverse Events
Time Frame: Postoperatively during inpatient stay and during readmissions up to 30 days postoperatively
Morbidity will be graded by Clavien Classification of adverse events
Postoperatively during inpatient stay and during readmissions up to 30 days postoperatively
Participants Admitted to Post-operative Intensive Care Unit (ICU)
Time Frame: up to 30 days post-surgery
up to 30 days post-surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, Los Angeles

Investigators

  • Principal Investigator: Michael Yeh, MD, University of California, Los Angeles

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 5, 2017

Primary Completion (Actual)

January 31, 2020

Study Completion (Actual)

October 10, 2021

Study Registration Dates

First Submitted

May 31, 2017

First Submitted That Met QC Criteria

June 2, 2017

First Posted (Actual)

June 5, 2017

Study Record Updates

Last Update Posted (Actual)

November 20, 2023

Last Update Submitted That Met QC Criteria

November 2, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB#17-000048

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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