Clinical Trial for the Prevention of Vasovagal Syncope

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

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.

Study Overview

• Status: Completed
• Conditions: Syncope, Vasovagal, Neurally-Mediated
• Intervention / Treatment: Drug: fludrocortisone acetate

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.

• Study Type: Interventional
• Enrollment (Actual): 213
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Alberta Children's Hospital
    • Calgary, Alberta, Canada, T2N 4N1
      • University of Calgary, Faculty of Medicine
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • St. Boniface General Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • Queen Elizabeth II, Halifax Infirmary
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • McMaster University, Hamilton Health Sciences
    • Kingston, Ontario, Canada, K7V 2V7
      • Queen's University
    • London, Ontario, Canada, N6A 5A5
      • University of Western Ontario, London Health Sciences
    • Ottawa, Ontario, Canada, K1Y 4W7
      • University of Ottawa, Ottawa Heart Institute
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
  • Quebec
    • Montreal, Quebec, Canada, H1T 1C8
      • Institut de Cardiologie de Montreal
    • Montreal, Quebec, Canada, H4J 1C5
      • Hopital Sacre Coeur de Montreal
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University
  • Tennessee
    • Nashville, Tennessee, United States, 37232-2195
      • Vanderbilt University
  • Virginia
    • Richmond, Virginia, United States, 23225-3838
      • Virginia Cardiovascular Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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	Drug: fludrocortisone acetate; Fludrocortisone acetate to a maximum of 0.2 mg daily Placebo to a maximum of 0.2 mg daily
Experimental: fludrocortisone acetate	Drug: fludrocortisone acetate; Fludrocortisone acetate to a maximum of 0.2 mg daily Placebo to a maximum of 0.2 mg daily

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Calgary
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Robert S. Sheldon, MD PhD, University of Calgary, Faculty of Medicine

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: June 30, 2005
• First Submitted That Met QC Criteria: June 30, 2005
• First Posted (Estimate): July 11, 2005

Study Record Updates

• Last Update Posted (Actual): October 15, 2019
• Last Update Submitted That Met QC Criteria: September 24, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: quality of life; randomized clinical trial; vasovagal syncope
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Autonomic Nervous System Diseases; Unconsciousness; Consciousness Disorders; Primary Dysautonomias; Orthostatic Intolerance; Syncope; Syncope, Vasovagal; Anti-Inflammatory Agents; Fludrocortisone
• Other Study ID Numbers: 130312; ISRCTN51802652