Preoperative Alpha Blockade for Pheochromocytoma
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|ClinicalTrials.gov Identifier: NCT03176693|
Recruitment Status : Recruiting
First Posted : June 5, 2017
Last Update Posted : June 4, 2018
|Condition or disease||Intervention/treatment||Phase|
|Pheochromocytoma Paraganglioma||Drug: Phenoxybenzamine Drug: Doxazosin||Phase 3|
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 (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Randomized Controlled Trial of Preoperative Alpha Blockade for Pheochromocytoma|
|Actual Study Start Date :||May 5, 2017|
|Estimated Primary Completion Date :||May 2023|
|Estimated Study Completion Date :||May 2024|
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).
Non-selective alpha blocker
Other Name: Dibenzyline
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).
Selective alpha blocker
Other Name: Cardura
- Hemodynamic instability [ Time Frame: Intraoperative ]Arterial line blood pressure measurements will be extracted from the electronic medical record every 60 seconds. The area under the curve outside predefined blood pressure thresholds (systolic blood pressure > 160, < 80) will be summed to create a hemodynamic instability index. The hemodynamic instability index will be compared between phenoxybenzamine and doxazosin arms.
- Mortality [ Time Frame: 30 days postoperatively ]Death within 30 days of surgery
- Drug versus inpatient costs [ Time Frame: Preoperative (2-3 weeks prior to surgery) and inpatient (typical hospital stay < 1 week) ]The average wholesale price of the drug will be used in combination with the patient's cost per pill to estimate drug costs. Inpatient costs will be captured by charges after applying cost to charge ratios. Preoperative drug costs and inpatient costs will be compared between phenoxybenzamine and doxazosin arms.
- Quality of life [ 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
- Morbidity [ Time Frame: Postoperatively during inpatient stay and during readmissions up to 30 days postoperatively ]Morbidity will be graded by Clavien Classification
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03176693
|Contact: Eric J Kuo, MDfirstname.lastname@example.org|
|Contact: Masha J Livhits, MDemail@example.com|
|United States, California|
|University of California, Los angeles||Recruiting|
|Los Angeles, California, United States, 90025|
|Principal Investigator: Masha J Livhits, MD|
|Sub-Investigator: Eric J Kuo, MD|
|Principal Investigator:||Michael Yeh, MD||University of California, Los Angeles|