Vasovagal SyncopePhase 4POST 4NCT01456481
Assessment of Midodrine in the Prevention of Vasovagal Syncope: The Prevention of Syncope Trial IV
A Phase 4 study testing midodrine hydrochloride in people with Vasovagal Syncope, run by Dr. Bob Sheldon at 17 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Vasovagal Syncope
- What is being tested?
- midodrine hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 134 participants
- Where
- 17 sitesin 3 countries
- Study dates
- Nov 2011to 31 Dec 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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,
Show all 12Show fewer
- 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.
Trial locations and contacts
17 sites in 3 countries.
17 sites in 3 countries
Canada14 sites
University of Calgary
Calgary, Alberta, T2N 4Z6
Alberta Health Services - Royal Alexandra Hospital
Edmonton, Alberta, T5H 3V9
Royal Alexandra Hospital
Edmonton, Alberta, T5H 3V9
Queen E II Health Sciences Centre
Halifax, Nova Scotia, B3H 3A6
Hamilton Health Sciences
Hamilton, Ontario, L8L 2X2
Hopital Sacre Coeur de Montreal
Montreal, Quebec, H4J 1C5
University of Ottawa Heart Institute
Ottawa, Ontario, K1Y 4W7
Red Deer Regional Hospital
Red Deer, Alberta, T4N 4E7
Prairie Vascular Research Network/Regina General Hospital
Regina, Saskatchewan, S4P 0W5
New Brunswick Heart Centre
Saint John, New Brunswick, E2L 4L2
Saskatoon Cardiology Consultants/Royal University Hospital
Saskatoon, Saskatchewan, S7K 3H1
Centre Hospitalier Universitaire de Sherbrooke
Sherbrooke, Quebec, J1H 5N4
St. Boniface General Hospital
St. Boniface, Manitoba, R2H 2A6
Victoria Cardiac Arrythmia Trials
Victoria, British Columbia, V8R 4R2
United States2 sites
University of Minnesota
Minneapolis, Minnesota, 55455
Vanderbilt University
Nashville, Tennessee, 37232
About this study
Official title: Assessment of Midodrine in the Prevention of Vasovagal Syncope: The Prevention of Syncope Trial IV (Post 4)
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
- Being tested
- midodrine hydrochloride, matching placebo
- Keywords
- reflex fainting, vasovagal syncope, midodrine
- Medical subject headings
- Syncope, Vasovagal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
midodrine hydrochlorideDrug
Also called Brand name for the drug is midodrine.
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.
matching placeboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| midodrine hydrochloride pills | Active comparator | Not described Receives: Drug: midodrine hydrochloride |
| oral placebo or sugar pill | Placebo comparator | Not described Receives: Drug: midodrine hydrochloride; Drug: matching placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome measure will be the proportion of patients having at least one syncope recurrence.
Measured: 1 year.
Secondary outcomes (4)
A secondary outcome will be the time between the first and second syncope recurrences.
Measured: 1 year
A secondary outcome will be the frequency of syncopal spells.
Measured: 1 year
A secondary outcome is the number, duration, and severity of presyncopal spells (as measured with the Calgary Presyncope Scale(19)).
Measured: 1 year.
A secondary outcomes will be quality of life as measured by the EQ-5D and the ISQL.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2011 (estimated)
- Study startNov 2011
- Primary completion20 Dec 2018
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Vasovagal SyncopeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 134 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. Bob Sheldon
- Sponsor type
- University, hospital or other
- Collaborators
- Vanderbilt University
- Responsible party
- Sponsor-investigator, Dr. Bob Sheldon, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01456481
- Sponsor's protocol ID
- CIHR#243314
- Acronym
- POST 4
- Status last verified
- May 2024
- First submitted
- 14 Oct 2011
- Last updated
- 9 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 34339231Raj 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.
PubMed 22610268
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Midodrine in the Prevention of Vasovagal Syncope: The Prevention of Syncope Trial IV (Post 4)
- ClinicalTrials.gov ID
- NCT01456481
- Acronym / sponsor ID
- POST 4 / CIHR#243314
- Conditions
- Vasovagal Syncope
- Keywords
- reflex fainting, vasovagal syncope, midodrine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 134 participants (actual)
- Lead sponsor
- Dr. Bob SheldonUniversity, hospital or other
- Collaborators
- Vanderbilt University
- Study start
- Nov 2011
- Primary completion
- 20 Dec 2018 (actual)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 20 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| midodrine hydrochloride pills | Active comparator | Drug: midodrine hydrochloride |
| oral placebo or sugar pill | Placebo comparator | Drug: midodrine hydrochloride, Drug: matching placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients will be eligible if they have:
Key exclusion criteria (12 listed)
- Patients will be excluded if they have:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| midodrine hydrochlorideAlso: Brand name for the drug is midodrine.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. | Drug | midodrine hydrochloride pills, oral placebo or sugar pill |
| matching placeboThe 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. | Drug | oral placebo or sugar pill |
Primary outcome
The primary outcome measure will be the proportion of patients having at least one syncope recurrence.
Time frame: 1 year.
4 secondary outcomes
A secondary outcome will be the time between the first and second syncope recurrences.
Time frame: 1 year
A secondary outcome will be the frequency of syncopal spells.
Time frame: 1 year
A secondary outcome is the number, duration, and severity of presyncopal spells (as measured with the Calgary Presyncope Scale(19)).
Time frame: 1 year.
A secondary outcomes will be quality of life as measured by the EQ-5D and the ISQL.
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2024.
- Derived from this study: PubMed 34339231Sheldon 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.
- Derived from this study: PubMed 22610268Raj 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.
Related trials for Vasovagal Syncope
RecruitingObservational study
Fainting Detection And Early Warning In Syncope Evaluation Study (ARISE)
Orthostatic Hypotension, Reflex Syncope
Active, not recruiting
Cardioneuroablation for Reflex Syncope and Exercise Capacity
Syncope, Vasovagal
RecruitingObservational study
Biospecimen Repository for Cardiac Arrhythmias at the Cleveland Clinic
Arrhythmias, Cardiac
Recruiting
Total Underwater Colonoscopy (TUC) for Improved Colorectal Cancer Screening: A Randomized Controlled Trial
Colorectal Neoplasia, Screening Colonoscopy
Active, not recruitingObservational study
A Warning Red Flag Classification System to Predict Risk of Vasovagal Event During Office Hysteroscopy
Vasovagal Syncope (VVS), Presyncope
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
17 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing midodrine hydrochloride in people with Vasovagal Syncope, run by Dr. Bob Sheldon at 17 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Canada, United States, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary outcome measure will be the proportion of patients having at least one syncope recurrence. (time frame: 1 year.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01456481, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2024.