Phenoxybenzamine Versus Doxazosin in PCC Patients

Condition(s) targeted: Pheochromocytoma

Intervention: Phenoxybenzamine (Drug); Doxazosin (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: University Medical Centre Groningen

Official(s) and/or principal investigator(s):
Michiel N. Kerstens, MD PhD, Study Director, Affiliation: University Medical Centre Groningen
Thera P. Links, MD PhD, Principal Investigator, Affiliation: University Medical Centre Groningen
Gütz J. Wietasch, MD PhD, Principal Investigator, Affiliation: University Medical Centre Groningen
Jaques W. Lenders, MD PhD, Principal Investigator, Affiliation: UMC St Radboud Nijmegen
G D. Valk, MD PhD, Principal Investigator, Affiliation: UMC Utrecht
E M. Eekhoff, MD PhD, Principal Investigator, Affiliation: Free University UMC Amsterdam
P H. Bisschop, MD PhD, Principal Investigator, Affiliation: Academical Medical Center Amsterdam
R A Feelders, MD PhD, Principal Investigator, Affiliation: Erasmus Medical Center Rotterdam
Bas Havekes, MD PhD, Principal Investigator, Affiliation: Maastricht University Medical Center
Peter Oomen, MD PhD, Principal Investigator, Affiliation: Medical Center Leeuwarden
I Eland, MD PhD, Principal Investigator, Affiliation: St. Antonius Ziekenhuis Nieuwegein
P H. Geelhoed- Duijvestijn, MD PhD, Principal Investigator, Affiliation: Medisch Centrum Haaglanden
P Groote Veldman, MD PhD, Principal Investigator, Affiliation: Medisch Spectrum Twente
H R Haak, MD PhD, Principal Investigator, Affiliation: Máxima Medisch Centrum
J R. Meinardi, MD PhD, Principal Investigator, Affiliation: Canisius-Wilhelmina Hospital
C B. Brouwer, MD PhD, Principal Investigator, Affiliation: Canisius-Wilhelmina Hospital
P L. van Battum, MD, Principal Investigator, Affiliation: Atrium Medical Center
A A. Franken, MD PhD, Principal Investigator, Affiliation: Isala Klinieken Zwolle

Overall contact:
Michiel N Kerstens, MD PhD, Phone: 0031- 50-3613962, Email: m.n.kerstens@int.umcg.nl

- 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 frequency

of intraoperative blood pressure episodes 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.

Official title: Pheochromocytoma Randomised Study Comparing Adrenoreceptor Inhibiting Agents for Preoperative Treatment

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: The number of patients demonstrating more than three intraoperative episodes of 5 minutes with blood pressure outside the predefined target range after pretreatment with either phenoxybenzamine or doxazosin.

Secondary outcome:

To attain preoperative blood pressure target values without co-medication

Resolution of (paroxysmal) symptoms and signs of pheochromocytoma.

Need for additional antihypertensive agents

Adverse effects of study medication

Length of preoperative treatment in either outpatient or inpatient clinic.

Control of blood pressure and heart rate.

Length of hospital stay.

Composite semi-quantitative score of intra- and postoperative hemodynamic control.

Postoperative hypoglycaemia

Perioperative mortality.

Perioperative cardiovascular morbidity.

Composite endpoint of perioperative mortality and perioperative cardiovascular morbidity.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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

Michiel N Kerstens, MD PhD, Phone: 0031- 50-3613962, Email: m.n.kerstens@int.umcg.nl

Department of Endocrinology, University Medical Center Groningen, Groningen 9700 RB, Netherlands; Recruiting
Michiel N. Kerstens, MD PhD, Phone: 0031-50-3613962, Email: m.n.kerstens@int.umcg.nl
Thera P. Links, MD PhD, Principal Investigator
Gütz J. Wietasch, MD PhD, Principal Investigator

Related publications:

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Starting date: December 2011
Last updated: January 25, 2012