Preoperative Alpha Blockade for Pheochromocytoma

Phase 3

Completed

• Conditions: Paraganglioma; Pheochromocytoma
• Interventions: Drug: Phenoxybenzamine; Drug: Doxazosin

• Registration Number: NCT03176693
• Lead Sponsor: University of California, Los Angeles

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.

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 Timeline

• Study Start: 2017-05-05
• Study First Submitted: 2017-05-31
• Study First Submitted QC: 2017-06-02
• Study First Posted: 2017-06-05
• Primary Completion: 2020-01-31
• Study Completion: 2021-10-10
• Results First Submitted: 2022-01-08
• Status Verified: 2023-11
• Results First Submitted QC: 2023-11-02
• Last Update Submitted: 2023-11-02
• Results First Posted: 2023-11-20
• Last Update Posted: 2023-11-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 39

Inclusion Criteria

• Adults with pheochromocytoma / paraganglioma undergoing surgical resection

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Exclusion Criteria

• Children < 18 years

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phenoxybenzamine	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).
Doxazosin	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).

Primary Outcome Measures

Name	Time	Method
Hemodynamic Instability	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.

Secondary Outcome Measures

Name	Time	Method
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)	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
Participants Admitted to Post-operative Intensive Care Unit (ICU)	up to 30 days post-surgery
Mortality	30 days postoperatively	Death within 30 days of surgery
Morbidity as Assessed by Occurrence of Adverse Events	Postoperatively during inpatient stay and during readmissions up to 30 days postoperatively	Morbidity will be graded by Clavien Classification of adverse events

Trial Locations

Locations (1)

University of California, Los angeles; 🇺🇸 Los Angeles, California, United States