Phenoxybenzamine Versus Doxazosin in PCC Patients
Information source: University Medical Centre Groningen
Information obtained from ClinicalTrials.gov on February 07, 2013
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pheochromocytoma
Intervention: Phenoxybenzamine (Drug); Doxazosin (Drug)
Phase: Phase 4
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
Michiel N Kerstens, MD PhD, Phone: 0031- 50-3613962, Email: firstname.lastname@example.org
- 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
- 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
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.
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.
Perioperative cardiovascular morbidity.
Composite endpoint of perioperative mortality and perioperative cardiovascular morbidity.
Minimum age: 18 Years.
Maximum age: N/A.
- age > 18 years
- diagnosis of benign Pheochromocytoma (adrenal or extra-adrenal, sporadic or
- 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
- age < 18 years
- malignant PCC, i. e. presence of lesions on imaging studies suggestive of distant
- severe hemodynamic instability before surgery necessitating admission to intensive
- incapability to adhere to the study protocol
Locations and Contacts
Michiel N Kerstens, MD PhD, Phone: 0031- 50-3613962, Email: email@example.com
Department of Endocrinology, University Medical Center Groningen, Groningen 9700 RB, Netherlands; Recruiting
Michiel N. Kerstens, MD PhD, Phone: 0031-50-3613962, Email: firstname.lastname@example.org
Thera P. Links, MD PhD, Principal Investigator
Gütz J. Wietasch, MD PhD, Principal Investigator
Lenders JW, Eisenhofer G, Mannelli M, Pacak K. Phaeochromocytoma. Lancet. 2005 Aug 20-26;366(9486):665-75. Review.
Lenders JW, Eisenhofer G, Armando I, Keiser HR, Goldstein DS, Kopin IJ. Determination of metanephrines in plasma by liquid chromatography with electrochemical detection. Clin Chem. 1993 Jan;39(1):97-103.
Beard CM, Sheps SG, Kurland LT, Carney JA, Lie JT. Occurrence of pheochromocytoma in Rochester, Minnesota, 1950 through 1979. Mayo Clin Proc. 1983 Dec;58(12):802-4.
Neumann HP, Cybulla M, Shibata H, Oya M, Naruse M, Higashihara E, Terachi T, Ling H, Takami H, Shuin T, Murai M. New genetic causes of pheochromocytoma: current concepts and the clinical relevance. Keio J Med. 2005 Mar;54(1):15-21. Review.
Amar L, Bertherat J, Baudin E, Ajzenberg C, Bressac-de Paillerets B, Chabre O, Chamontin B, Delemer B, Giraud S, Murat A, Niccoli-Sire P, Richard S, Rohmer V, Sadoul JL, Strompf L, Schlumberger M, Bertagna X, Plouin PF, Jeunemaitre X, Gimenez-Roqueplo AP. Genetic testing in pheochromocytoma or functional paraganglioma. J Clin Oncol. 2005 Dec 1;23(34):8812-8.
Korpershoek E, Van Nederveen FH, Dannenberg H, Petri BJ, Komminoth P, Perren A, Lenders JW, Verhofstad AA, De Herder WW, De Krijger RR, Dinjens WN. Genetic analyses of apparently sporadic pheochromocytomas: the Rotterdam experience. Ann N Y Acad Sci. 2006 Aug;1073:138-48.
Gimenez-Roqueplo AP, Lehnert H, Mannelli M, Neumann H, Opocher G, Maher ER, Plouin PF; European Network for the Study of Adrenal Tumours (ENS@T) Pheochromocytoma Working Group. Phaeochromocytoma, new genes and screening strategies. Clin Endocrinol (Oxf). 2006 Dec;65(6):699-705.
Qin Y, Yao L, King EE, Buddavarapu K, Lenci RE, Chocron ES, Lechleiter JD, Sass M, Aronin N, Schiavi F, Boaretto F, Opocher G, Toledo RA, Toledo SP, Stiles C, Aguiar RC, Dahia PL. Germline mutations in TMEM127 confer susceptibility to pheochromocytoma. Nat Genet. 2010 Mar;42(3):229-33. Epub 2010 Feb 14.
Pacak K, Eisenhofer G, Ahlman H, Bornstein SR, Gimenez-Roqueplo AP, Grossman AB, Kimura N, Mannelli M, McNicol AM, Tischler AS; International Symposium on Pheochromocytoma. Pheochromocytoma: recommendations for clinical practice from the First International Symposium. October 2005. Nat Clin Pract Endocrinol Metab. 2007 Feb;3(2):92-102.
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.
Pacak K. Preoperative management of the pheochromocytoma patient. J Clin Endocrinol Metab. 2007 Nov;92(11):4069-79. Review.
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. Epub 2002 Jun 19.
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. Epub 2009 Dec 4.
van der Horst-Schrivers AN, Kerstens MN, Wolffenbuttel BH. Preoperative pharmacological management of phaeochromocytoma. Neth J Med. 2006 Sep;64(8):290-5. Review.
Eisenhofer G, Rivers G, Rosas AL, Quezado Z, Manger WM, Pacak K. Adverse drug reactions in patients with phaeochromocytoma: incidence, prevention and management. Drug Saf. 2007;30(11):1031-62. Review.
Kinney MA, Warner ME, vanHeerden JA, Horlocker TT, Young WF Jr, Schroeder DR, Maxson PM, Warner MA. Perianesthetic risks and outcomes of pheochromocytoma and paraganglioma resection. Anesth Analg. 2000 Nov;91(5):1118-23.
Eisenhofer G, Bornstein SR. Surgery: Risks of hemodynamic instability in pheochromocytoma. Nat Rev Endocrinol. 2010 Jun;6(6):301-2. No abstract available.
Karthikeyan G, Moncur RA, Levine O, Heels-Ansdell D, Chan MT, Alonso-Coello P, Yusuf S, Sessler D, Villar JC, Berwanger O, McQueen M, Mathew A, Hill S, Gibson S, Berry C, Yeh HM, Devereaux PJ. Is a pre-operative brain natriuretic peptide or N-terminal pro-B-type natriuretic peptide measurement an independent predictor of adverse cardiovascular outcomes within 30 days of noncardiac surgery? A systematic review and meta-analysis of observational studies. J Am Coll Cardiol. 2009 Oct 20;54(17):1599-606. Review.
Kim AW, Quiros RM, Maxhimer JB, El-Ganzouri AR, Prinz RA. Outcome of laparoscopic adrenalectomy for pheochromocytomas vs aldosteronomas. Arch Surg. 2004 May;139(5):526-9; discussion 529-31.
Shen WT, Grogan R, Vriens M, Clark OH, Duh QY. One hundred two patients with pheochromocytoma treated at a single institution since the introduction of laparoscopic adrenalectomy. Arch Surg. 2010 Sep;145(9):893-7.
Kocak S, Aydintug S, Canakci N. Alpha blockade in preoperative preparation of patients with pheochromocytomas. Int Surg. 2002 Jul-Sep;87(3):191-4.
Weingarten TN, Cata JP, O'Hara JF, Prybilla DJ, Pike TL, Thompson GB, Grant CS, Warner DO, Bravo E, Sprung J. Comparison of two preoperative medical management strategies for laparoscopic resection of pheochromocytoma. Urology. 2010 Aug;76(2):508.e6-11. Epub 2010 May 23.
Mueller T, Gegenhuber A, Dieplinger B, Poelz W, Haltmayer M. Capability of B-type natriuretic peptide (BNP) and amino-terminal proBNP as indicators of cardiac structural disease in asymptomatic patients with systemic arterial hypertension. Clin Chem. 2005 Dec;51(12):2245-51. Epub 2005 Oct 13.
Starting date: December 2011
Last updated: January 25, 2012