Clinical Trial for the Prevention of Vasovagal Syncope

NCT ID: NCT00118482

Last Updated: 2019-10-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 213 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-05-31
• Study Completion Date: 2011-07-31

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.

Conditions

Syncope, Vasovagal, Neurally-Mediated

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

fludrocortisone acetate

Group Type: EXPERIMENTAL

fludrocortisone acetate

Intervention Type: DRUG

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

Placebo

Group Type: PLACEBO_COMPARATOR

fludrocortisone acetate

Intervention Type: DRUG

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

Interventions

fludrocortisone acetate

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

Intervention Type: DRUG

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

• Minimum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

University of Calgary

OTHER

Sponsor Role: lead

Responsible Party

Dr. Bob Sheldon

Professor of Cardiac Sciences, Medicine and Medical Genetics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Robert S. Sheldon, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University of Calgary, Faculty of Medicine

Locations

Boston University

Boston, Massachusetts, United States

Vanderbilt University

Nashville, Tennessee, United States

Virginia Cardiovascular Specialists

Richmond, Virginia, United States

University of Calgary, Faculty of Medicine

Calgary, Alberta, Canada

Alberta Children's Hospital

Calgary, Alberta, Canada

St. Boniface General Hospital

Winnipeg, Manitoba, Canada

Queen Elizabeth II, Halifax Infirmary

Halifax, Nova Scotia, Canada

McMaster University, Hamilton Health Sciences

Hamilton, Ontario, Canada

Queen's University

Kingston, Ontario, Canada

University of Western Ontario, London Health Sciences

London, Ontario, Canada

University of Ottawa, Ottawa Heart Institute

Ottawa, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

Institut de Cardiologie de Montreal

Montreal, Quebec, Canada

Hopital Sacre Coeur de Montreal

Montreal, Quebec, Canada

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 29766871 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27364043 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 16781217 (View on PubMed)

Other Identifiers

ISRCTN51802652

Identifier Type: -

Identifier Source: secondary_id

130312

Identifier Type: -

Identifier Source: org_study_id