Ignite Creation Date:
2024-05-06 @ 2:48 AM
Last Modification Date:
2024-10-26 @ 11:23 AM
Study NCT ID:
NCT02123056
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-05-09
First Post:
2014-04-23
Brief Title:
Assessment of Metoprolol in the Prevention of Vasovagal Syncope in Aging Subjects
Sponsor:
University of Calgary
Organization:
University of Calgary
Study Overview
Official Title:
Assessment of Metoprolol in the Prevention of Vasovagal Syncope in Aging Subjects
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Syncope affects about 50 of Canadians is the cause of 1-2 of emergency room visits and probably is responsible for CDN 250 million in health care spending each year It is associated with decreased quality of life trauma loss of employment and limitations in daily activities The most common cause is vasovagal syncope
This occurs in people of all ages and is a lifelong predilection While the median number of faints in the population is 2 those who come to the investigators care have a median 10-15 lifetime spells and have an increased frequency in the year before presentation Vasovagal syncope is due to abrupt hypotension and transient bradycardia which cause cerebral hypoperfusion The pathophysiology may be either failure of venous return or progressive vasodilation both due to inappropriately low sympathetic outflow Sympathetic stimulation might be involved early in the reflex cascade There is no known medical treatment for frequent fainting The investigators performed the pivotal CIHR-funded randomized trials that showed that neither permanent pacing beta blockers nor fludrocortisone help the majority of patients
However 3 observational studies suggested that beta blockers prevent syncope in older subjects and the Prevention of Syncope Trial POST1 showed in a prespecified -stratified analysis that patients 42 years tended to benefit The investigators recent meta-analysis showed a benefit from metoprolol in these patients with a hazard ratio of 052 CI 027 to 101 and an age-specific response to beta blockers p 0007 These results suggest the need for a randomized clinical trial of metoprolol for the prevention of vasovagal syncope in older subjects Accordinglythe investigators conducted a poll of 48 cardiologists and neurologists in Canada and abroad 98 stated that a randomized trial was necessary and 92 agreed to participate in such a trial Separately this study emerged as the first choice for syncope randomized trials after consultation with Canadian and international experts
Objective To determine if treatment with metoprolol in patients 40 years old with moderate to severely frequent vasovagal syncope will better suppress syncope recurrences than placebo
Methods This will be a longitudinal prospective parallel design placebo-controlled randomized clinical trial
Patients will be enrolled during a recruitment period of 4 years and followed for a fixed period of 1 year Subjects will have had 1 faint in the previous year and a diagnosis of vasovagal syncope based on a quantitative diagnostic score They will be randomized to receive either metoprolol or placebo at an initial dose of 50 mg bid Dose adjustments will be made according to treating physician discretion to optimize tolerance and compliance while maximizing dose The primary outcome measure will be the time to the first recurrence of syncope after a 2 week dose titration wash-in period over the 1-year observation period The primary analysis will be performed on an intention-to-treat basis Secondary analyses will include an on-treatment analysis as well as analyses comparing syncope and presyncope frequency number needed to treat quality of life impact of syncope on daily living and cost from the perspective of the publicly funded health care system The investigators will enroll 248 patients to have an 85 power to detect a reduction p005 in the primary outcome from 50 placebo group to 30 midodrine group a 40 relative risk reduction This sample size also allows for a 11 rate of subject dropout with loss to follow-up before a syncopal event The University of Calgary Syncope Clinic has a well-functioning clinical trial apparatus that successfully completed the randomized multicenter Prevention of Syncope Trials POST1 metoprolol for vasovagal syncope POST2 fludrocortisone for vasovagal syncope and SIRCAT Statin-Induced Reduction of Cardiomyopathy Trial Enrolment is underway in the CIHR-funded POST3 pacing versus loop recorders in syncope patients with bifascicular block and POST4 midodrine for vasovagal syncope Study centres that were highly productive in POST1-4 have agreed to participate The investigators therefore will have ample syncope enrolling centres
Relevance This study will provide evidence to inform the use of metoprolol in the treatment of moderate to severely frequent syncope in older patients with vasovagal syncope Given the lack of any other conventional medical therapy the investigators expect it to have rapid impact on care
This occurs in people of all ages and is a lifelong predilection While the median number of faints in the population is 2 those who come to the investigators care have a median 10-15 lifetime spells and have an increased frequency in the year before presentation Vasovagal syncope is due to abrupt hypotension and transient bradycardia which cause cerebral hypoperfusion The pathophysiology may be either failure of venous return or progressive vasodilation both due to inappropriately low sympathetic outflow Sympathetic stimulation might be involved early in the reflex cascade There is no known medical treatment for frequent fainting The investigators performed the pivotal CIHR-funded randomized trials that showed that neither permanent pacing beta blockers nor fludrocortisone help the majority of patients
However 3 observational studies suggested that beta blockers prevent syncope in older subjects and the Prevention of Syncope Trial POST1 showed in a prespecified -stratified analysis that patients 42 years tended to benefit The investigators recent meta-analysis showed a benefit from metoprolol in these patients with a hazard ratio of 052 CI 027 to 101 and an age-specific response to beta blockers p 0007 These results suggest the need for a randomized clinical trial of metoprolol for the prevention of vasovagal syncope in older subjects Accordinglythe investigators conducted a poll of 48 cardiologists and neurologists in Canada and abroad 98 stated that a randomized trial was necessary and 92 agreed to participate in such a trial Separately this study emerged as the first choice for syncope randomized trials after consultation with Canadian and international experts
Objective To determine if treatment with metoprolol in patients 40 years old with moderate to severely frequent vasovagal syncope will better suppress syncope recurrences than placebo
Methods This will be a longitudinal prospective parallel design placebo-controlled randomized clinical trial
Patients will be enrolled during a recruitment period of 4 years and followed for a fixed period of 1 year Subjects will have had 1 faint in the previous year and a diagnosis of vasovagal syncope based on a quantitative diagnostic score They will be randomized to receive either metoprolol or placebo at an initial dose of 50 mg bid Dose adjustments will be made according to treating physician discretion to optimize tolerance and compliance while maximizing dose The primary outcome measure will be the time to the first recurrence of syncope after a 2 week dose titration wash-in period over the 1-year observation period The primary analysis will be performed on an intention-to-treat basis Secondary analyses will include an on-treatment analysis as well as analyses comparing syncope and presyncope frequency number needed to treat quality of life impact of syncope on daily living and cost from the perspective of the publicly funded health care system The investigators will enroll 248 patients to have an 85 power to detect a reduction p005 in the primary outcome from 50 placebo group to 30 midodrine group a 40 relative risk reduction This sample size also allows for a 11 rate of subject dropout with loss to follow-up before a syncopal event The University of Calgary Syncope Clinic has a well-functioning clinical trial apparatus that successfully completed the randomized multicenter Prevention of Syncope Trials POST1 metoprolol for vasovagal syncope POST2 fludrocortisone for vasovagal syncope and SIRCAT Statin-Induced Reduction of Cardiomyopathy Trial Enrolment is underway in the CIHR-funded POST3 pacing versus loop recorders in syncope patients with bifascicular block and POST4 midodrine for vasovagal syncope Study centres that were highly productive in POST1-4 have agreed to participate The investigators therefore will have ample syncope enrolling centres
Relevance This study will provide evidence to inform the use of metoprolol in the treatment of moderate to severely frequent syncope in older patients with vasovagal syncope Given the lack of any other conventional medical therapy the investigators expect it to have rapid impact on care
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None