Assessment of Midodrine in the Prevention of Vasovagal Syncope: The Prevention of Syncope Trial IV

Study Overview
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Brief Summary
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About 20% of adults faint recurrently. These patients are often highly symptomatic, have problems with employment and driving and have reduced quality of life. There are no therapies that have withstood the test of adequately designed and conducted randomized clinical trials. Midodrine is a prodrug whose metabolite is an alpha-1 adrenergic agonist that increases venous return to the heart and raises blood pressure. There is considerable lower level evidence that it might prevent vasovagal syncope. The investigators will test the hypothesis that Midodrine prevents recurrences of syncope in patients with moderate to severe vasovagal syncope.

Official Title
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Assessment of Midodrine in the Prevention of Vasovagal Syncope: The Prevention of Syncope Trial IV (Post 4)

Conditions
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Vasovagal Syncope

Intervention / Treatment
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* Drug: midodrine hydrochloride
* Drug: matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients will be eligible if they have: ≥2 syncopal spells in the year preceding enrolment, and ≥ -2 points on the Syncope Symptom Score for Structurally Normal hearts, and Age ≥ 18 years with informed consent. Exclusion Criteria: Patients will be excluded if they have: other causes of syncope, such as ventricular tachycardia, complete heart block, postural 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 permanent pacemaker, a seizure disorder, urinary retention, hypertension defined as >140/90 mm Hg, hepatic disease, glaucoma or a 5-minute stand test resulting in diagnoses of Postural Orthostatic Tachycardia Syndrome or Orthostatic Hypotension.

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Active Comparator: midodrine hydrochloride pills<br> | Drug: midodrine hydrochloride<br>* Target dose is midodrine hydrochloride or placebo pills 10 mg three times a day for 12 months. The starting dose is 5mg q4h x3, and if tolerated a forced titration up to 10mg/dose. If there is an intolerance, then the dose can be reduced to 2.5mg/dose.<br>* Other names: Brand name for the drug is midodrine.;|
| Placebo Comparator: oral placebo or sugar pill<br> | Drug: midodrine hydrochloride<br>* Target dose is midodrine hydrochloride or placebo pills 10 mg three times a day for 12 months. The starting dose is 5mg q4h x3, and if tolerated a forced titration up to 10mg/dose. If there is an intolerance, then the dose can be reduced to 2.5mg/dose.<br>* Other names: Brand name for the drug is midodrine.;Drug: matching placebo<br>* The target dose in this study is 10mg q4h x3 for 12 months. The starting dose is 5mg q4h x3, and if tolerated a forced titration up to 10mg/dose. If there is an intolerance, then the dose can be reduced to 2.5mg/dose.<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 proportion of patients having at least one syncope recurrence. |  | 1 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A secondary outcome will be the time between the first and second syncope recurrences. |  | 1 year | 
| A secondary outcome will be the frequency of syncopal spells. |  | 1 year | 
| A secondary outcome is the number, duration, and severity of presyncopal spells (as measured with the Calgary Presyncope Scale(19)). |  | 1 year. | 
| A secondary outcomes will be quality of life as measured by the EQ-5D and the ISQL. |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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reflex fainting, vasovagal syncope, midodrine