Phenoxybenzamine Versus Doxazosin in PCC Patients

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

Interventions

DRUG

Phenoxybenzamine

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.)

DRUG

Doxazosin

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.)

Sponsors & Collaborators

• Radboud University Medical Center

  collaborator OTHER

• UMC Utrecht

  collaborator OTHER

• VU University of Amsterdam

  collaborator OTHER

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

  collaborator OTHER

• Leiden University Medical Center

  collaborator OTHER

• Erasmus Medical Center

  collaborator OTHER

• Maastricht University Medical Center

  collaborator OTHER

• St. Antonius Hospital

  collaborator OTHER

• Medisch Spectrum Twente

  collaborator OTHER

• Maxima Medical Center

  collaborator OTHER

• Canisius-Wilhelmina Hospital

  collaborator OTHER

• Onze Lieve Vrouwe Gasthuis

  collaborator OTHER

• Atrium Medical Center

  collaborator OTHER

• Isala

  collaborator OTHER

• University Medical Center Groningen

  lead OTHER

Principal Investigators

• Michiel N. Kerstens, MD PhD · University Medical Center Groningen

• Thera P. Links, MD PhD · University Medical Center Groningen

• Gütz J. Wietasch, MD PhD · University Medical Center Groningen

• Jaques W. Lenders, MD PhD · UMC St Radboud Nijmegen

• G D. Valk, MD PhD · UMC Utrecht

• E M. Eekhoff, MD PhD · Free University UMC Amsterdam

• P H. Bisschop, MD PhD · Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

• R A Feelders, MD PhD · Erasmus Medical Center

• Bas Havekes, MD PhD · Maastricht University Medical Center

• Peter Oomen, MD PhD · medical center leeuwarden

• I Eland, MD PhD · St. Antonius Ziekenhuis Nieuwegein

• P H. Geelhoed- Duijvestijn, MD PhD · Medical Center Haaglanden

• P Groote Veldman, MD PhD · Medisch Spectrum Twente

• H R Haak, MD PhD · Máxima Medisch Centrum

• J R. Meinardi, MD PhD · Canisius-Wilhelmina Hospital

• C B. Brouwer, MD PhD · Canisius-Wilhelmina Hospital

• P L. van Battum, MD · Atrium Medical Center

• A A. Franken, MD PhD · Isala

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-12-31

Primary Completion

2018-01-31

Completion

2018-01-31

Countries

• Netherlands

Study Locations