Clinical Trial for the Prevention of Vasovagal Syncope

Study Overview
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Brief Summary
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The main question in the study is whether people taking fludrocortisone are less likely to faint than people taking an inactive pill called a placebo. Fludrocortisone is a drug that stimulates the body to retain salt and water. The investigators know from some studies that it might prevent people from fainting at home and in the community, while they are carrying on with their lives. There is some evidence that salt and water retention help prevent fainting, but no one has a clear idea about whether this is true. This study will try to determine if that is true.

Detailed Description
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About 10% of adults faint recurrently. These patients are often highly symptomatic, have problems with employment and driving, and have well-documented reduced quality of life. There are no therapies that have withstood the test of adequately conducted and credible randomized clinical trials. There is ample evidence of the importance of blood volume in the pathophysiology of vasovagal syncope. Fludrocortisone acetate is a corticosteroid with a mild enhancement of glucocorticoid activity and a marked increase in mineralocorticoid activity. It has no appreciable glucocorticoid effect at doses between 0.05 to 0.2 mg, which are the commonly used clinical doses for various disorders requiring mineralocorticoid adrenal replacement. The acute actions of fludrocortisone acetate are sodium and water retention, at the expense of urinary potassium excretion. Blood volume expansion with either dietary salt supplementation or fludrocortisone is often recommended by clinicians for the treatment of vasovagal syncope despite a paucity of good evidence for their efficacy. Four clinical studies suggest its utility in the prevention of syncope. Fludrocortisone might decrease the incidence of vasovagal syncope, but the quality of the evidence supporting its use is poor. There are no randomized, placebo-controlled trials of fludrocortisone for the prevention of vasovagal syncope. In this 5-year study the investigators will test the hypothesis that fludrocortisone prevents recurrences of vasovagal syncope.

Official Title
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A Randomized Clinical Trial of Fludrocortisone for Vasovagal Syncope: The Second Prevention of Syncope Trial (POST II)

Conditions
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Syncope, Vasovagal, Neurally-Mediated

Intervention / Treatment
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* Drug: fludrocortisone acetate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Syncope as a cause of loss of consciousness according to European Society of Cardiology criteria > 2 lifetime syncopal spells preceding enrollment > or = to -2 points on the Syncope Symptom Score for Structurally Normal Hearts Age > 18 years with informed consent, or age > 14 years with consent and informed parental consent Exclusion Criteria: Other causes of syncope, such as ventricular tachycardia, complete heart block, postural (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 A known intolerance to fludrocortisone Another clinical need for fludrocortisone that cannot be met with other drugs A permanent pacemaker A seizure disorder A major chronic non cardiovascular disease Hypertension (blood pressure ≥ 130/85 on 2 occasions) or heart failure Renal dysfunction (baseline glomerular filtration rate reduced below 60 ml/min/1.73m2 according to the Cockroft-Gault formula) Diabetes mellitus Hepatic disease Glaucoma Any prior use of fludrocortisone acetate A 5-minute stand test resulting in diagnosis of postural orthostatic tachycardia syndrome or orthostatic hypotension

Ages Eligible for Study
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Minimum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: fludrocortisone acetate<br> | Drug: fludrocortisone acetate<br>* Fludrocortisone acetate to a maximum of 0.2 mg daily Placebo to a maximum of 0.2 mg daily<br>|
| Placebo Comparator: Placebo<br> | Drug: fludrocortisone acetate<br>* Fludrocortisone acetate to a maximum of 0.2 mg daily Placebo to a maximum of 0.2 mg daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary Outcome Measure Will be the Recurrence of Syncope in Follow up Period. | This will be measured in terms of number of patients that had at least 1 syncopal spell in the 12 month follow up period. | Within 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Frequency of Syncope Will be the First Secondary Outcome Measure. | Frequency will be reported as 12- month syncope event rates (%) | Within 12 months | 
| Presyncope Frequency, Duration, and Intensity Will be the Second Secondary Outcome Measures, Both Alone and in a Composite Score. |  | Within 12 months | 
| Quality of Life Will be the Third Secondary Outcome Measure. The Investigators Will Compare the Quality of Life in Treated and Untreated Patients. | Quality of life will be the third secondary outcome measure. The investigators will compare the quality of life in patients on fludrocortisone vs placebo. Reported as RAND36 (Research ANd Development) score. The RAND 36-Item Health Survey taps eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. It also includes a single item that provides an indication of perceived change in health. Min value = 0 , Maximum value = 100. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vasovagal syncope, randomized clinical trial, quality of life