Clinical Trial for the Prevention of Vasovagal Syncope

• ClinicalTrials.gov Identifier: NCT00118482
• Recruitment Status: Completed
• First Posted: July 11, 2005
• Results First Posted: June 28, 2017
• Last Update Posted: October 15, 2019
• Sponsor: University of Calgary
• Collaborator: Canadian Institutes of Health Research (CIHR)
• Information provided by (Responsible Party): Dr. Bob Sheldon, University of Calgary

Tracking Information

• First Submitted Date: June 30, 2005
• First Posted Date: July 11, 2005
• Results First Submitted Date: October 26, 2016
• Results First Posted Date: June 28, 2017
• Last Update Posted Date: October 15, 2019
• Study Start Date: May 2005
• Actual Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 25, 2017)

The Primary Outcome Measure Will be the Recurrence of Syncope in Follow up Period. [ Time Frame: Within 12 months ]

This will be measured in terms of number of patients that had at least 1 syncopal spell in the 12 month follow up period.

• Original Primary Outcome Measures (submitted: June 30, 2005): The primary outcome measure will be the time to the first recurrence of syncope.

Current Secondary Outcome Measures (submitted: September 24, 2019)

• The Frequency of Syncope Will be the First Secondary Outcome Measure. [ Time Frame: Within 12 months ]
  Frequency will be reported as 12- month syncope event rates (%)
• Presyncope Frequency, Duration, and Intensity Will be the Second Secondary Outcome Measures, Both Alone and in a Composite Score. [ Time Frame: 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. [ Time Frame: 12 months ]
  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.

Original Secondary Outcome Measures (submitted: June 30, 2005)

• The frequency of syncope will be the first secondary outcome measure.
• Presyncope frequency, duration, and intensity will be the second secondary outcome measures, both alone and in a composite score.
• Quality of life will be the third secondary outcome measure. The investigators will compare the quality of life in treated and untreated patients.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)

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.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Syncope, Vasovagal, Neurally-Mediated

Intervention

Drug: fludrocortisone acetate

Fludrocortisone acetate to a maximum of 0.2 mg daily Placebo to a maximum of 0.2 mg daily

Study Arms

• Experimental: fludrocortisone acetate
  Intervention: Drug: fludrocortisone acetate
• Placebo Comparator: Placebo
  Intervention: Drug: fludrocortisone acetate

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 25, 2017): 213
• Original Enrollment (submitted: June 30, 2005): 310
• Actual Study Completion Date: July 2011
• Actual Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 14 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT00118482
• Other Study ID Numbers: 130312; ISRCTN51802652
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Dr. Bob Sheldon, University of Calgary
• Original Responsible Party: Not Provided
• Current Study Sponsor: University of Calgary
• Original Study Sponsor: Same as current
• Collaborators: Canadian Institutes of Health Research (CIHR)

Investigators

• Principal Investigator: Robert S. Sheldon, MD PhD; University of Calgary, Faculty of Medicine

• PRS Account: University of Calgary
• Verification Date: September 2019