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

NCT01456481 | Active Not Recruiting Phase 4 DMC

• 1 other identifier: CIHR#243314
• Study Type: interventional
• Target: 134
• Locations: 3 countries
• Sites: 17

Brief Summary

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.

Conditions

Vasovagal Syncope

Keywords

reflex fainting; vasovagal syncope; midodrine

Outcome Measures

Primary Outcomes (1)

• The primary outcome measure will be the proportion of patients having at least one syncope recurrence.

  1 year.

Secondary Outcomes (4)

• 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

Study Arms (2)

midodrine hydrochloride pills

ACTIVE COMPARATOR

Drug: midodrine hydrochloride

oral placebo or sugar pill

PLACEBO COMPARATOR

Drug: midodrine hydrochloride; Drug: matching placebo

Interventions

midodrine hydrochloride DRUG

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.

Also known as: Brand name for the drug is midodrine.

midodrine hydrochloride pills; oral placebo or sugar pill

matching placebo DRUG

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.

oral placebo or sugar pill

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dr. Bob Sheldon: lead
• Vanderbilt University: collaborator

Study Sites (17)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

Alberta Health Services - Royal Alexandra Hospital

Edmonton, Alberta, T5H 3V9, Canada

Location

Royal Alexandra Hospital

Edmonton, Alberta, T5H 3V9, Canada

Location

Red Deer Regional Hospital

Red Deer, Alberta, T4N 4E7, Canada

Location

Victoria Cardiac Arrythmia Trials

Victoria, British Columbia, V8R 4R2, Canada

Location

St. Boniface General Hospital

St. Boniface, Manitoba, R2H 2A6, Canada

Location

New Brunswick Heart Centre

Saint John, New Brunswick, E2L 4L2, Canada

Location

Queen E II Health Sciences Centre

Halifax, Nova Scotia, B3H 3A6, Canada

Location

Hamilton Health Sciences

Hamilton, Ontario, L8L 2X2, Canada

Location

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

Hopital Sacre Coeur de Montreal

Montreal, Quebec, H4J 1C5, Canada

Location

Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Prairie Vascular Research Network/Regina General Hospital

Regina, Saskatchewan, S4P 0W5, Canada

Location

Saskatoon Cardiology Consultants/Royal University Hospital

Saskatoon, Saskatchewan, S7K 3H1, Canada

Location

Medical University of Lodz

Lodz, 93-005, Poland

Location

Related Publications (2)

• Sheldon R, Faris P, Tang A, Ayala-Paredes F, Guzman J, Marquez M, Morillo CA, Krahn AD, Kus T, Ritchie D, Safdar S, Maxey C, Raj SR; POST 4 investigators. Midodrine for the Prevention of Vasovagal Syncope : A Randomized Clinical Trial. Ann Intern Med. 2021 Oct;174(10):1349-1356. doi: 10.7326/M20-5415. Epub 2021 Aug 3.

  PMID: 34339231 DERIVED

• Raj SR, Faris PD, McRae M, Sheldon RS. Rationale for the prevention of syncope trial IV: assessment of midodrine. Clin Auton Res. 2012 Dec;22(6):275-80. doi: 10.1007/s10286-012-0167-5. Epub 2012 May 19.

  PMID: 22610268 DERIVED

MeSH Terms

Conditions

Syncope, Vasovagal

Interventions

Midodrine

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Syncope; Unconsciousness; Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Cardiac Sciences, Medicine and Medical Genetics

Study Record Dates

• First Submitted: October 14, 2011
• First Posted: October 20, 2011
• Study Start: November 1, 2011
• Primary Completion: December 20, 2018
• Study Completion: December 31, 2024
• Last Updated: May 9, 2024

Record last verified: 2024-05

Locations

PL (1); US (2); CA (14)