Phenoxybenzamine Versus Doxazosin in PCC Patients

NCT01379898 | Completed Phase 4

• 2 other identifiers: PRESCRIPT2010.3692010:022417-25
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 1

Brief Summary

• Rationale: The optimal preoperative medical management for patients with a pheochromocytoma is currently unknown. In particular, there is no agreement with respect to whether phenoxybenzamine or doxazosin is the optimal alfa-adrenoreceptor antagonist to be administered before surgical resection of a pheochromocytoma. We hypothesized that the competitive alfa1-antagonist doxazosin is superior to the non-competitive alfa1- and alfa2-antagonist phenoxybenzamine.
• Objective: comparing effects of preoperative treatment with either phenoxybenzamine or doxazosin on intraoperative hemodynamic control in patients undergoing surgical resection of a pheochromocytoma.
• Study design: Randomised controlled open-label trial.
• Study population: 18 - 55 yr old. Adult patients with a recently diagnosed benign pheochromocytoma.
• Intervention: Patients are randomised to receive oral treatment with either phenoxybenzamine or doxazosin preoperatively.
• Main study parameters/endpoints: The main study parameter is defined as the percentage of intraoperative time that blood pressure is outside the predefined target range after pretreatment with either phenoxybenzamine or doxazosin. In this multicenter trial, we compare the effects of two commonly used drugs in patients being medically prepared for resection of a benign pheochromocytoma. Participants are not subjected to an experimental treatment of any kind, as we merely aim to describe in detail the perioperative course in general and, in particular, the intraoperative hemodynamic control in patients treated preoperatively with either phenoxybenzamine or doxazosin. A routine diagnostic work-up for pheochromocytoma will be performed in all participants. One extra blood sample (volume: 48,5 mL) is drawn before start of the study medication, and participants need to record their symptoms in a diary. In addition, patients who are pretreated in the outpatient clinic monitor their blood pressure and pulse rate at home with an automated device. Treatment with an alfa-adrenoreceptor antagonist is initiated at least 2 - 3 weeks prior to surgery. Patients who are admitted to the hospital for pretreatment with an alfa-adrenoreceptor antagonist have their blood pressure and pulse rate measured by the nursing staff. The final site visit is planned at 30 days after surgery, in line with current practice.

Conditions

Pheochromocytoma

Keywords

Pheochromocytoma; Doxazosin; Phenoxybenzamine

Outcome Measures

Primary Outcomes (1)

• The main study parameter is defined as the percentage of intraoperative time that blood pressure is outside the predefined target range after pretreatment with either phenoxybenzamine or doxazosin.

  Blood pressure and heart rate will be monitored continuesly during surgery.

  Duration of surgery, i.e. on average 3 hours

Secondary Outcomes (12)

• To attain preoperative blood pressure target values without co-medication

  an expected average of 2 to 6 weeks before surgery

• Resolution of (paroxysmal) symptoms and signs of pheochromocytoma.

  an expected average of 2-6 weeks before surgery

• Need for additional antihypertensive agents

  an expected average of 2-6 weeks before surgery

• Adverse effects of study medication

  an expected average of 2-6 weeks before surgery

• Length of preoperative treatment in either outpatient or inpatient clinic.

  an expected average of 2-6 weeks before surgery

Study Arms (2)

Phenoxybezamine

ACTIVE COMPARATOR

Phenoxybenzamine (capsules 10 mg, once to twice daily) is administered orally, starting 2-3 weeks before planned resection of PCC.

Drug: Phenoxybenzamine

Doxazosin

ACTIVE COMPARATOR

Phenoxybenzamine (slow release tablets 4 or 8 mg, once to twice daily) is administered orally, starting 2-3 weeks before planned resection of PCC.

Drug: Doxazosin

Interventions

Phenoxybenzamine DRUG

Starting dosage of phenoxybenzamine in hypertensive subjects:20 mg q.d. (=10 mg b.i.d.) and in normotensive subjects 10 mg q.d. (in the evening). Dose escalation until blood pressure targets are reached, with a maximum dose of 140 mg q.d. (=70 mg b.i.d.)

Also known as: Dibenzyran

Phenoxybezamine

Doxazosin DRUG

Starting dosage of doxazosine in hypertensive subjects:8 mg q.d. (=4 mg b.i.d.)and in normotensive subjects starting dose 4 mg q.d. (in the evening). Dose escalation until blood pressure targets are reached, with a maximum dose of 48 mg q.d. .(=24 mg b.i.d.)

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:

• age \> 18 years
• diagnosis of benign Pheochromocytoma (adrenal or extra-adrenal, sporadic or hereditary:
• hypertension
• elevated plasma and/or urinary (nor)metanephrines. From each patient, a blood sample is collected for measurement of plasma (nor)metanephrines with the reference laboratory assay (i.e. XLC-MS/MS) at the Department of Laboratory Medicine of the UMCG.
• localisation of PCC by anatomical (MRI/CT) and functional imaging (I123-MIBG scintigraphy or 18F-DOPA PET)
• planned for surgical removal of the PCC

You may not qualify if:

• age \< 18 years
• malignant PCC, i.e. presence of lesions on imaging studies suggestive of distant metastases
• severe hemodynamic instability before surgery necessitating admission to intensive care unit
• pregnancy
• incapability to adhere to the study protocol

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Radboud University Medical Center: collaborator
• UMC Utrecht: collaborator
• VU University of Amsterdam: collaborator
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator
• Leiden University Medical Center: collaborator
• Erasmus Medical Center: collaborator
• Maastricht University Medical Center: collaborator
• St. Antonius Hospital: collaborator
• Medisch Spectrum Twente: collaborator
• Maxima Medical Center: collaborator
• Canisius-Wilhelmina Hospital: collaborator
• Onze Lieve Vrouwe Gasthuis: collaborator
• Atrium Medical Center: collaborator
• Isala: collaborator

Study Sites (1)

Department of Endocrinology, University Medical Center Groningen

Groningen, 9700 RB, Netherlands

Location

Related Publications (24)

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• Plouin PF, Duclos JM, Soppelsa F, Boublil G, Chatellier G. Factors associated with perioperative morbidity and mortality in patients with pheochromocytoma: analysis of 165 operations at a single center. J Clin Endocrinol Metab. 2001 Apr;86(4):1480-6. doi: 10.1210/jcem.86.4.7392.

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• Pacak K. Preoperative management of the pheochromocytoma patient. J Clin Endocrinol Metab. 2007 Nov;92(11):4069-79. doi: 10.1210/jc.2007-1720.

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• 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 BACKGROUND

• Bruynzeel H, Feelders RA, Groenland TH, van den Meiracker AH, van Eijck CH, Lange JF, de Herder WW, Kazemier G. Risk Factors for Hemodynamic Instability during Surgery for Pheochromocytoma. J Clin Endocrinol Metab. 2010 Feb;95(2):678-85. doi: 10.1210/jc.2009-1051. Epub 2009 Dec 4.

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  PMID: 31714582 DERIVED

MeSH Terms

Conditions

Pheochromocytoma

Interventions

Phenoxybenzamine; Doxazosin

Condition Hierarchy (Ancestors)

Paraganglioma; 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

Study Officials

• Michiel N. Kerstens, MD PhD

  University Medical Center Groningen

  STUDY DIRECTOR

• Thera P. Links, MD PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

• Gütz J. Wietasch, MD PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

• Jaques W. Lenders, MD PhD

  UMC St Radboud Nijmegen

  PRINCIPAL INVESTIGATOR

• G D. Valk, MD PhD

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

• E M. Eekhoff, MD PhD

  Free University UMC Amsterdam

  PRINCIPAL INVESTIGATOR

• P H. Bisschop, MD PhD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

• R A Feelders, MD PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

• Bas Havekes, MD PhD

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

• Peter Oomen, MD PhD

  medical center leeuwarden

  PRINCIPAL INVESTIGATOR

• I Eland, MD PhD

  St. Antonius Ziekenhuis Nieuwegein

  PRINCIPAL INVESTIGATOR

• P H. Geelhoed- Duijvestijn, MD PhD

  Medical Center Haaglanden

  PRINCIPAL INVESTIGATOR

• P Groote Veldman, MD PhD

  Medisch Spectrum Twente

  PRINCIPAL INVESTIGATOR

• H R Haak, MD PhD

  Máxima Medisch Centrum

  PRINCIPAL INVESTIGATOR

• J R. Meinardi, MD PhD

  Canisius-Wilhelmina Hospital

  PRINCIPAL INVESTIGATOR

• C B. Brouwer, MD PhD

  Canisius-Wilhelmina Hospital

  PRINCIPAL INVESTIGATOR

• P L. van Battum, MD

  Atrium Medical Center

  PRINCIPAL INVESTIGATOR

• A A. Franken, MD PhD

  Isala

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2011
• First Posted: June 23, 2011
• Study Start: December 1, 2011
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2018
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

NL (1)