A Proof of Principal Study of Atomoxetine for the Prevention of Vasovagal Syncope

Syncope, Vasovagal Clinical Trial

— POST6  

Official title:

A Proof of Principal Study of Atomoxetine for the Prevention of Vasovagal Syncope (POST 6)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02874937
• Other study ID #: ucalgary
• Status: Completed
• Phase: Phase 2
• Start date: February 2015
• Est. completion date: January 8, 2018

Study information

• Verified date: May 2019
• Source: University of Calgary
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Syncope affects about 50% of Canadians, is the cause of 1-2% of emergency room visits, and probably is responsible for CDN $250 million in health care spending each year.There is no known medical treatment for frequent fainting. Two randomized studies suggest that inhibition of norepinephrine transport (NET) reuptake with sibutramine and reboxetine (NET inhibitors) prevents syncope on tilt testing by about 80%, and the investigators reported that sibutramine markedly reduced the frequency of vasovagal syncope in 7 of our most symptomatic patients. Sibutramine and reboxetine, for different reasons, are not available in Canada. However atomoxetine is available and is used to help patients with attention deficit disorder. There are no data pertaining to its hemodynamic effects in patients with vasovagal syncope. Although a randomized clinical trial of atomoxetine for the prevention of vasovagal syncope would be needed before clinical use, the investigators first need a proof of principle study. The objective is to determine in a prospective, randomized, parallel, double-blind study if atomoxetine 40 mg bid in patients at least 18 years old with recurrent vasovagal syncope will better prevent syncope during tilt testing than placebo.

Description:

Study Design: This will be a randomized, double-blind, parallel-arm study in which the subjects will undergo a tilt table test following 2 doses of atomoxetine 40mg PO (evening before and morning of study) or after 2 doses of matching placebo (on separate days). On the morning of the study, the fasting subject (except for medications) will be instrumented, on an empty bladder. ECG electrodes will be applied to monitor continuous heart rhythm. Blood pressure will be monitored continuously using a finger volume clamp method using one or more of several extant devices, and calibrated with intermittent brachial cuff measurements. One intravenous cannula will be placed in the contralateral arm (to the blood pressure cuff) for blood sampling.

Tilt Table Protocol: Following the insertion of the venous cannulae, a period of at least 20 minutes will be allowed to elapse before a 10-minute basal control (baseline) period. Baseline data will be digitally recorded in this time. In the last 5 minutes of this period, blood will be drawn for fractionated plasma catecholamines. The table will be rapidly raised to 80 degrees for up to 60 minutes. The investigators are deliberately avoiding tilt test methods with provocative medications to avoid the issue of multiple causal factors. At 10 minutes and 30 minutes following onset of tilt (or at the onset of severe presyncope or hypotension [systolic blood pressure <70 mmHg]), venous fractionated catecholamines will be sampled. The study will be terminated if the subject develops hypotension with severe presyncopal symptoms associated with a systolic blood pressure ≤70 mmHg or at the completion of the protocol.

A sample size of 56 syncope patients will have 85% power to detect a 60% relative risk reduction from a placebo outcome rate of 65%, using an unmatched 2-tailed test with alpha=0.05. To compensate for the report dropout rate the investigators will inflate the sample by 15% to 64 subjects. A formal, blinded mid-way safety and efficacy analysis will be performed with a p<0.05 stopping rule for efficacy. This also will provide 85% power to detect an 80% relative risk reduction.

Randomization will be carried out using a computerized algorithm. Patients will be randomized in a double blind fashion to receive atomoxetine 40mg PO x2 or matching placebo with a 1:1 randomization ratio. Medication containers will be centrally filled and labeled with the randomization code number.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: January 8, 2018
• Est. primary completion date: November 28, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• =1 syncopal spells in the year preceding enrolment

• =-2 points on the Calgary Syncope Symptom Score

• Age =18 years with informed consent

• The Calgary Syncope Symptom Score is used to diagnose VVS in patients with structurally normal hearts

Exclusion Criteria:

• Other causes of syncope, such as ventricular tachycardia, complete heart block, orthostatic hypotension or hypersensitive carotid sinus syndrome

• An inability to give informed consent

• Important valvular, coronary, myocardial or conduction abnormality or significant arrhythmia

• Hypertrophic cardiomyopathy

• Permanent pacemaker

• Seizure disorder

• Hypertension defined as >150/90 mm Hg

• Pregnancy

• Glaucoma

• Medications with known effects on blood pressure

• Known hypersensitivity to atomoxetine and derivatives

• Other factors which, in the investigator's opinion, would prevent the subject from completing the protocol.

Related Conditions & MeSH terms

• Syncope
• Syncope, Vasovagal

Intervention

Drug:
• Atomoxetine
norepinephrine transporter inhibitor
• Matching Placebo
matching placebo identical in appearance.

Locations

Country	Name	City	State
Canada	University of Calgary, Faculty of Medicine	Calgary	Alberta

Sponsors (1)

Lead Sponsor	Collaborator
University of Calgary

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to syncope or presyncope		1 hour
Secondary	systemic vascular resistance		1 hour
Secondary	stroke volume		1 hour
Secondary	cardiac output		1 hour
Secondary	catecholamine levels		1 hour