ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 25 of 74 for:    "hereditary paraganglioma-pheochromocytoma" OR "Paraganglioma"

Preoperative Alpha Blockade for Pheochromocytoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03176693
Recruitment Status : Recruiting
First Posted : June 5, 2017
Last Update Posted : June 4, 2018
Sponsor:
Information provided by (Responsible Party):
Michael Yeh, 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.

Condition or disease Intervention/treatment Phase
Pheochromocytoma Paraganglioma Drug: Phenoxybenzamine Drug: Doxazosin Phase 3

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  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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


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 Name: 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 Name: Cardura




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Mortality [ Time Frame: 30 days postoperatively ]
    Death within 30 days of surgery

  2. 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.

  3. 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

  4. Morbidity [ Time Frame: Postoperatively during inpatient stay and during readmissions up to 30 days postoperatively ]
    Morbidity will be graded by Clavien Classification



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults with pheochromocytoma / paraganglioma undergoing surgical resection

Exclusion Criteria:

  • Children < 18 years

Information from the National Library of Medicine

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


Contacts
Contact: Eric J Kuo, MD 310-206-0585 ekuo@mednet.ucla.edu
Contact: Masha J Livhits, MD 310-206-0585 mlivhits@mednet.ucla.edu

Locations
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         
Sponsors and Collaborators
University of California, Los Angeles
Investigators
Principal Investigator: Michael Yeh, MD University of California, Los Angeles

Publications of Results:
Other Publications:
Responsible Party: Michael Yeh, Assistant Professor of Surgery, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT03176693     History of Changes
Other Study ID Numbers: IRB#17-000048
First Posted: June 5, 2017    Key Record Dates
Last Update Posted: June 4, 2018
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
Paraganglioma
Carotid Body Tumor
Paraganglioma, Extra-Adrenal
Pheochromocytoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Doxazosin
Phenoxybenzamine
Antihypertensive Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Vasodilator Agents