Clinical trial NCT00118482: Clinical Trial for the Prevention of Vasovagal Syncope
Official title: A Randomized Clinical Trial of Fludrocortisone for Vasovagal Syncope: The Second Prevention of Syncope Trial (POST II)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Syncope, Vasovagal, Neurally-Mediated
Keywords: vasovagal syncope
randomized clinical trial
quality of life
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2005-07-11
Enrollment: 213
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: The Primary Outcome Measure Will be the Recurrence of Syncope in Follow up Period.
timeFrame: Within 12 months
Secondary outcomes:
measure: The Frequency of Syncope Will be the First Secondary Outcome Measure.
timeFrame: Within 12 months
measure: Presyncope Frequency, Duration, and Intensity Will be the Second Secondary Outcome Measures, Both Alone and in a Composite Score.
timeFrame: Within 12 months
measure: Quality of Life Will be the Third Secondary Outcome Measure. The Investigators Will Compare the Quality of Life in Treated and Untreated Patients.
timeFrame: 12 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston University
state: Massachusetts
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Richmond
country: United States
facility: Virginia Cardiovascular Specialists
state: Virginia
city: Calgary
country: Canada
facility: University of Calgary, Faculty of Medicine
state: Alberta
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Winnipeg
country: Canada
facility: St. Boniface General Hospital
state: Manitoba
city: Halifax
country: Canada
facility: Queen Elizabeth II, Halifax Infirmary
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster University, Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Queen's University
state: Ontario
city: London
country: Canada
facility: University of Western Ontario, London Health Sciences
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa, Ottawa Heart Institute
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Montreal
country: Canada
facility: Institut de Cardiologie de Montreal
state: Quebec
city: Montreal
country: Canada
facility: Hopital Sacre Coeur de Montreal
state: Quebec
Study officials:
affiliation: University of Calgary, Faculty of Medicine
name: Robert S. Sheldon, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sheldon R, Raj SR, Rose MS, Morillo CA, Krahn AD, Medina E, Talajic M, Kus T, Seifer CM, Lelonek M, Klingenheben T, Parkash R, Ritchie D, McRae M; POST 2 Investigators. Fludrocortisone for the Prevention of Vasovagal Syncope: A Randomized, Placebo-Controlled Trial. J Am Coll Cardiol. 2016 Jul 5;68(1):1-9. doi: 10.1016/j.jacc.2016.04.030.
citation: Tan VH, Ritchie D, Maxey C, Sheldon R; POST Investigators. Prospective Assessment of the Risk of Vasovagal Syncope During Driving. JACC Clin Electrophysiol. 2016 Apr;2(2):203-208. doi: 10.1016/j.jacep.2015.10.006. Epub 2015 Nov 17.
citation: Raj SR, Rose S, Ritchie D, Sheldon RS; POST II Investigators. The Second Prevention of Syncope Trial (POST II)--a randomized clinical trial of fludrocortisone for the prevention of neurally mediated syncope: rationale and study design. Am Heart J. 2006 Jun;151(6):1186.e11-7. doi: 10.1016/j.ahj.2006.03.013.