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.

Timeline

Start

2011-12

Primary completion

2018-01

Completion

2018-01

Publications

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• Background 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. doi: 10.1196/annals.1353.014.
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• Background 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. doi: 10.1097/00000539-200011000-00013.
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• Background 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. doi: 10.1373/clinchem.2005.056648. Epub 2005 Oct 13.
• Buitenwerf E, Osinga TE, Timmers HJLM, Lenders JWM, Feelders RA, Eekhoff EMW, Haak HR, Corssmit EPM, Bisschop PHLT, Valk GD, Veldman RG, Dullaart RPF, Links TP, Voogd MF, Wietasch GJKG, Kerstens MN. Efficacy of alpha-Blockers on Hemodynamic Control during Pheochromocytoma Resection: A Randomized Controlled Trial. J Clin Endocrinol Metab. 2020 Jul 1;105(7):2381-91. doi: 10.1210/clinem/dgz188.

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