Phenoxybenzamine Versus Doxazosin in PCC Patients

• Status: Completed
• Trial end date: 2018-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

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

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