Syncope, Vasovagal, Neurally-Mediated
Conditions
Keywords
vasovagal syncope, randomized clinical trial, quality of life
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.
Interventions
Fludrocortisone acetate to a maximum of 0.2 mg daily Placebo to a maximum of 0.2 mg daily
Sponsors
Canadian Institutes of Health Research (CIHR)
University of Calgary
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
14 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Outcome Measure Will be the Recurrence of Syncope in Follow up Period. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Frequency of Syncope Will be the First Secondary Outcome Measure. | 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. | 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. | 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. |
Countries
Canada, United States
Participant flow
Recruitment details
Patients were recruited between October 1998 and April 2003 from university hospitals in Canada, Columbia, the United States and Poland.
Participants by arm
| Arm | Count |
|---|---|
| Fludrocortisone Acetate fludrocortisone acetate: Fludrocortisone acetate to a maximum of 0.2 mg daily Placebo to a maximum of 0.2 mg daily | 105 |
| Placebo fludrocortisone acetate: Fludrocortisone acetate to a maximum of 0.2 mg daily Placebo to a maximum of 0.2 mg daily | 105 |
| Total | 210 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 7 | 7 |
| Overall Study | Withdrawal by Subject | 23 | 22 |
Baseline characteristics
| Characteristic | Fludrocortisone Acetate | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 28 years STANDARD_DEVIATION 11.5 | 31 years STANDARD_DEVIATION 12 | 30.5 years STANDARD_DEVIATION 12 |
| Region of Enrollment Canada | 85 participants | 85 participants | 170 participants |
| Region of Enrollment United States | 8 participants | 8 participants | 16 participants |
| Sex: Female, Male Female | 71 Participants | 75 Participants | 146 Participants |
| Sex: Female, Male Male | 34 Participants | 30 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 105 | 8 / 105 |
| serious Total, serious adverse events | 0 / 105 | 0 / 105 |
Outcome results
Primary
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.
Time frame: Within 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fludrocortisone Acetate | The Primary Outcome Measure Will be the Recurrence of Syncope in Follow up Period. | 42 Participants |
| Placebo | The Primary Outcome Measure Will be the Recurrence of Syncope in Follow up Period. | 54 Participants |
Secondary
Presyncope Frequency, Duration, and Intensity Will be the Second Secondary Outcome Measures, Both Alone and in a Composite Score.
Time frame: Within 12 months
Population: Data not analyzed because of variability of data collected on presyncope
Secondary
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.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fludrocortisone Acetate | Quality of Life Will be the Third Secondary Outcome Measure. The Investigators Will Compare the Quality of Life in Treated and Untreated Patients. | 69 score on a scale | Standard Deviation 21 |
| Placebo | Quality of Life Will be the Third Secondary Outcome Measure. The Investigators Will Compare the Quality of Life in Treated and Untreated Patients. | 84 score on a scale | Standard Deviation 11 |
Secondary
The Frequency of Syncope Will be the First Secondary Outcome Measure.
Frequency will be reported as 12- month syncope event rates (%)
Time frame: Within 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Fludrocortisone Acetate | The Frequency of Syncope Will be the First Secondary Outcome Measure. | 44.0 rate % |
| Placebo | The Frequency of Syncope Will be the First Secondary Outcome Measure. | 60.5 rate % |