A Randomized Controlled Trial of Sertraline in Paroxysmal Arterial Hypertension (ATRAX)

A Randomized Controlled Trial of Sertraline in Paroxysmal Arterial Hypertension (ATRAX Trial)

There is currently no established treatment for paroxysmal hypertension, but selective serotonin reuptake inhibitors showed good effect in previous reports. This double-blind, placebo controlled, prospective multicenter clinical trial will assess the efficacy of sertraline on cessation or reduction of symptoms of paroxysmal arterial hypertension. 136 patients with documented hypertensive paroxysms with abrupt elevations of blood pressure and distressful physical symptoms will be randomized in a 1:1 ratio to receive sertraline, 50 mg daily, or matching placebo as an add-on to their chronic medication. Effect of the treatment on patient symptoms, office and ambulatory blood pressure and side effects will be evaluated after 3 months. If proven effective, sertraline might become a standard treatment for this condition.

Study Overview

• Status: Unknown
• Conditions: Hypertension
• Intervention / Treatment: Drug: Sertraline; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 136
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jan Vaclavik, MD. Ph.D. Assoc. Prof.; Phone Number: +420588442682; Email: janvaclavik@yahoo.com
• Study Contact Backup: Name: Irena Opavska, Bc.; Phone Number: +420588443716; Email: irena.opavska@fnol.cz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Study will enroll adult patients (age >18 years) with hypertensive paroxysms during the past 6 months (preferably during the past 6 weeks) - abrupt elevations of systolic blood pressure (BP) ≥20% compared to previous measured systolic BP value before paroxysm, or ≥20% compared to mean systolic BP on 24-hour ambulatory blood pressure monitoring (ABPM), or ≥20% compared to measured office systolic BP, documented by a clinician or home blood pressure monitor, requiring physician or emergency room visit or the use of any rescue antihypertensive medication. Hypertensive paroxysms may be accompanied by abrupt onset of one or more distressful physical symptoms, such as headache, chest pain, dizziness, nausea, palpitations, flushing, and diaphoresis.

Exclusion Criteria:

Pregnancy or breastfeeding, hypersensitivity to sertraline (Zoloft®) or of the the components of this drug. Current use of sertraline or any other selective serotonin reuptake inhibitor (SSRI), mono-amin oxidase (MAO) inhibitors, selegiline, moclobemide, linezolide, pimozide. Current use of other serotoninergic drugs (eg. tryptofane, triptane and other 5-HT agonists), tramadol or dopamine antagonists (including antipsychotics).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; placebo	Drug: Placebo; 1/2 tablet once daily for first 7 days, then 1 tablet once daily for the rest of the trial
Active Comparator: Sertraline; sertraline, 25 mg once daily for first 7 days, then 50 mg once daily for the rest of the trial	Drug: Sertraline; 25 mg once daily for first 7 days, then 50 mg once daily for the rest of the trial

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
difference in the rate of paroxysmal hypertension symptoms cessation between sertraline and placebo groups	3 months of treatment
difference in the rate of paroxysmal hypertension symptoms reduction between sertraline and placebo groups	3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
difference in the fall of mean office and ambulatory systolic and diastolic blood pressure between groups	3 months
side effects of the treatment	3 months

Collaborators and Investigators

• Sponsor: University Hospital Olomouc
• Collaborators: University Hospital Ostrava; Brno University Hospital; Tomas Bata Hospital, Czech Republic; Thomayer University Hospital; St. Anne; Prerov Hospital; Valasske Mezirici Hospital; Vsetin Hospital
• Investigators: Study Chair: Jan Vaclavik, MD. Ph.D. Assoc. Prof, University Hospital Olomouc

Publications and helpful links

General Publications

• Mann SJ. Severe paroxysmal hypertension (pseudopheochromocytoma): understanding the cause and treatment. Arch Intern Med. 1999 Apr 12;159(7):670-4. doi: 10.1001/archinte.159.7.670.
• Eisenhofer G, Sharabi Y, Pacak K. Unexplained symptomatic paroxysmal hypertension in pseudopheochromocytoma: a stress response disorder? Ann N Y Acad Sci. 2008 Dec;1148:469-78. doi: 10.1196/annals.1410.019.
• Pickering TG, Clemow L. Paroxysmal hypertension: the role of stress and psychological factors. J Clin Hypertens (Greenwich). 2008 Jul;10(7):575-81. doi: 10.1111/j.1751-7176.2008.07844.x.
• Mann SJ. Severe paroxysmal hypertension (pseudopheochromocytoma). Curr Hypertens Rep. 2008 Feb;10(1):12-8. doi: 10.1007/s11906-008-0005-2.

Helpful Links

• University Hospital Olomouc
• Faculty of Medicine and Dentistry, Palacký University

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2017
• Primary Completion (Anticipated): June 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: December 22, 2015
• First Submitted That Met QC Criteria: December 22, 2015
• First Posted (Estimate): December 29, 2015

Study Record Updates

• Last Update Posted (Actual): September 8, 2017
• Last Update Submitted That Met QC Criteria: September 5, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: paroxysmal hypertension; pseudopheochromocytoma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Sertraline
• Other Study ID Numbers: ATRAX

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes