Syncope, Vasovagal
Conditions
Keywords
Neurocardiogenic Syncope, Reflex Syncope, Fainting Spells
Brief summary
Syncope is defined as transient loss of consciousness associated with inability to maintain postural tone with rapid and spontaneous recovery. The purpose of this study is to assess the effects of sublingual administration of a new medication called CPC on tilt-induced syncope in patients with a history of vasovagal syncope (VVS) or near syncope. 140 participants will be randomized at the University of Wisconsin - Madison. Each participant will be in the study for 1 day.
Detailed description
Vasovagal syncope (VVS) is the most common type of syncope. The mechanism is reflex-mediated triggered by various afferent input to the brain. The event is usually preceded by diaphoresis, warmth, nausea, and pallor, and is followed by fatigue. While several drugs are indicated in the treatment of VVS, to our knowledge, there is no current treatment of an impending syncopal attack. In the present study, the investigators hypothesized that a single administration of sublingual CPC preparation during the prodromal phase would abort tilt-induced syncope or near syncope with SBP less than or equal to 70 mmHg in patients with a history of VVS. Patients with an established diagnosis of typical VVS or near syncope will be randomized to receive CPC or placebo in 1:1 ratio. Drug or placebo will be administered at the onset of prodromes during tilt table testing. In addition to the primary endpoint (syncope or near syncope with SBP less than or equal to 70 mmHg), the investigators will be assessing the effects of the drug on time to event, incidence of asystole (\> 3 sec), and fatigue after syncope.
Interventions
DRUGCPC - Capsaicin, Phenylephrine, Caffeine
CPC is a combination of Capsaicin, Phenylephrine and Caffeine
DIAGNOSTIC_TESTTilt Table Test
Participant will undergo tilt tablet testing using the Italian protocol (see reference section). The Italian protocol includes 20 minutes of passive tilt at 70 degrees (Passive Phase) followed by nitroglycerin (NTG) administration and tilt testing for another 15 minutes (NTG Phase).
DRUGPlacebo
Placebo for CPC
Sponsors
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Randomized 1:1 to CPC or placebo
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
1. Established diagnosis of typical vasovagal syncope or near syncope 2. Age 18-50 years
Exclusion criteria
1. Systolic BP \>130 mmHg 2. History of hypertension or cardiac arrhythmias 3. History of cardiovascular disease or cerebral ischemic events 4. Allergic reaction to any of the drug components 5. Contraindication to tilt testing 6. Any physical or psychological symptom, based on the clinical judgment of the investigators that would make a participant unsuitable for the study 7. Any use of a medication(s) based on the clinical judgment of the investigators that would make a participant unsuitable for the study (e.g. fludrocortisone, theophylline, prazosin, doxazosin, terazosin, MAO-inhibitors, pseudoephedrine, decongestant and PDE5 inhibitors). 8. Unwilling to discontinue Midodrine or beta-blocker therapy 48 hours before tilt table testing. 9. Women who are pregnant (confirmed with pregnancy test on day of study) or lactating.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Have Hypotensive Syncope or Near Syncope With SBP Less Than or Equal to 70 mmHG During Tilt Test | During tilt table testing (up to approximately 35 minutes) | Hypotensive syncope is defined as transient loss of consciousness associated with SBP less than or equal to 90 mmHg. Near syncope is defined as sensation of near fainting while still being responsive to verbal commands. Near syncope will be used as a primary endpoint only when it is associated with a SBP less than or equal to 70 mmHg. |
| Time to Syncope or Near-syncope After CPC or Placebo Administration | During tilt table testing (up to approximately 35 minutes) | Time in seconds from CPC or Placebo administration to syncope or near syncope in patients who had an event |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Have Asystolic Pauses > 3 Seconds in the CPC and Placebo Arms | During tilt table testing (up to approximately 35 minutes) | Percentage of Participants with an event who had asystolic pauses \> 3 seconds during syncope or near syncope |
| Fatigue Scores at 1, 4, and 8 Hours Post Tilt Table Testing | Up to 8 hours after tilt table testing (up to approximately 8 hours and 35 minutes) | Fatigue Scores at 1, 4 and 8 hours post tilt table testing in participants who had an event. Using standard continuous fatigue scale of 1 to 5, with 1 = no fatigue and 5 = max fatigue. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at the University of Wisconsin- Madison using general recruitment emails addressed to students, faculty and staff and UW Heath Faint and Fall Clinic patients. All participants signed electronic consents in advance of study visit. The first participant completed the study in July 2021, and the last participant completed the study in August 2023.
Pre-assignment details
Digital consent was obtained in 143 subjects. 14 subjects were not randomized for various reasons; no show (n=3), withdrew consent (n=4), SBP \> 130 mmHg (n=6) and not withholding Midodrine (n=1). A total of 129 subjects were randomized to CPC (n=66) or Placebo (n=63).
Participants by arm
| Arm | Count |
|---|---|
| CPC Adminstration Participant who were randomized to received CPC during Tilt Testing for which evaluable data was available. | 65 |
| Placebo Administration Participant who were randomized to received Placebo during Tilt Testing for which evaluable data was available. | 62 |
| Total | 127 |
Baseline characteristics
| Characteristic | Placebo Administration | Total | CPC Adminstration |
|---|---|---|---|
| Age, Continuous | 26.2 Years STANDARD_DEVIATION 7.5 | 26.2 Years STANDARD_DEVIATION 7.3 | 26.2 Years STANDARD_DEVIATION 7.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 6 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 55 Participants | 109 Participants | 54 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 12 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 11 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 17 Participants | 8 Participants |
| Race (NIH/OMB) White | 47 Participants | 95 Participants | 48 Participants |
| Region of Enrollment United States | 62 participants | 127 participants | 65 participants |
| Sex: Female, Male Female | 55 Participants | 110 Participants | 55 Participants |
| Sex: Female, Male Male | 7 Participants | 17 Participants | 10 Participants |
| Syncope History Participants with a history of syncope | 58 Participants | 118 Participants | 60 Participants |
| Syncope History Participant with a history of near syncope | 4 Participants | 9 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 66 | 0 / 63 |
| other Total, other adverse events | 3 / 66 | 4 / 63 |
| serious Total, serious adverse events | 0 / 66 | 0 / 63 |
Outcome results
Primary
Percentage of Participants Who Have Hypotensive Syncope or Near Syncope With SBP Less Than or Equal to 70 mmHG During Tilt Test
Hypotensive syncope is defined as transient loss of consciousness associated with SBP less than or equal to 90 mmHg. Near syncope is defined as sensation of near fainting while still being responsive to verbal commands. Near syncope will be used as a primary endpoint only when it is associated with a SBP less than or equal to 70 mmHg.
Time frame: During tilt table testing (up to approximately 35 minutes)
Population: Intention to treat based on randomized treatment assignment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CPC Adminstration | Percentage of Participants Who Have Hypotensive Syncope or Near Syncope With SBP Less Than or Equal to 70 mmHG During Tilt Test | Number of participants with syncope or near syncope event | 32 Participants |
| CPC Adminstration | Percentage of Participants Who Have Hypotensive Syncope or Near Syncope With SBP Less Than or Equal to 70 mmHG During Tilt Test | Number of participants without syncope or near syncope event | 33 Participants |
| Placebo Administration | Percentage of Participants Who Have Hypotensive Syncope or Near Syncope With SBP Less Than or Equal to 70 mmHG During Tilt Test | Number of participants with syncope or near syncope event | 27 Participants |
| Placebo Administration | Percentage of Participants Who Have Hypotensive Syncope or Near Syncope With SBP Less Than or Equal to 70 mmHG During Tilt Test | Number of participants without syncope or near syncope event | 35 Participants |
Comparison: Primary endpoint -- ITT primary endpoint analysisp-value: 0.521Large sample Z-test for population prop
Primary
Time to Syncope or Near-syncope After CPC or Placebo Administration
Time in seconds from CPC or Placebo administration to syncope or near syncope in patients who had an event
Time frame: During tilt table testing (up to approximately 35 minutes)
Population: Secondary endpoints analyses were limited to participants who had syncope or near syncope
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| CPC Adminstration | Time to Syncope or Near-syncope After CPC or Placebo Administration | 90.1 seconds | Standard Deviation 95 |
| Placebo Administration | Time to Syncope or Near-syncope After CPC or Placebo Administration | 76.9 seconds | Standard Deviation 95 |
Comparison: Secondary endpoint -- Time to event for evaluable ITT population who had a primary event.p-value: 0.574Log Rank
Secondary
Fatigue Scores at 1, 4, and 8 Hours Post Tilt Table Testing
Fatigue Scores at 1, 4 and 8 hours post tilt table testing in participants who had an event. Using standard continuous fatigue scale of 1 to 5, with 1 = no fatigue and 5 = max fatigue.
Time frame: Up to 8 hours after tilt table testing (up to approximately 8 hours and 35 minutes)
Population: Secondary endpoints analyses were limited to participants who had syncope or near syncope
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| CPC Adminstration | Fatigue Scores at 1, 4, and 8 Hours Post Tilt Table Testing | Fatigue rated at 1 hour post tilt test | 2.2 Score on a scale | Standard Deviation 1.05 |
| CPC Adminstration | Fatigue Scores at 1, 4, and 8 Hours Post Tilt Table Testing | Fatigue rated at 4 hour post tilt test | 2.2 Score on a scale | Standard Deviation 1.09 |
| CPC Adminstration | Fatigue Scores at 1, 4, and 8 Hours Post Tilt Table Testing | Fatigue rated at 8 hour post tilt test | 1.9 Score on a scale | Standard Deviation 0.91 |
| Placebo Administration | Fatigue Scores at 1, 4, and 8 Hours Post Tilt Table Testing | Fatigue rated at 1 hour post tilt test | 2.0 Score on a scale | Standard Deviation 0.85 |
| Placebo Administration | Fatigue Scores at 1, 4, and 8 Hours Post Tilt Table Testing | Fatigue rated at 4 hour post tilt test | 2.3 Score on a scale | Standard Deviation 1.07 |
| Placebo Administration | Fatigue Scores at 1, 4, and 8 Hours Post Tilt Table Testing | Fatigue rated at 8 hour post tilt test | 2.6 Score on a scale | Standard Deviation 1.39 |
Comparison: Secondary endpoint -- Measures of Fatigue for evaluable ITT population who had a primary event.p-value: 0.732Wilcoxon (Mann-Whitney)
Comparison: Secondary endpoint -- Measures of Fatigue for evaluable ITT population who had a primary event.p-value: 0.591Wilcoxon (Mann-Whitney)
Comparison: Secondary endpoint -- Measures of Fatigue for evaluable ITT population who had a primary event.p-value: 0.034Wilcoxon (Mann-Whitney)
Secondary
Percentage of Patients Who Have Asystolic Pauses > 3 Seconds in the CPC and Placebo Arms
Percentage of Participants with an event who had asystolic pauses \> 3 seconds during syncope or near syncope
Time frame: During tilt table testing (up to approximately 35 minutes)
Population: Secondary endpoints analyses were limited to participants who had syncope or near syncope
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CPC Adminstration | Percentage of Patients Who Have Asystolic Pauses > 3 Seconds in the CPC and Placebo Arms | 2 Participants |
| Placebo Administration | Percentage of Patients Who Have Asystolic Pauses > 3 Seconds in the CPC and Placebo Arms | 1 Participants |
Comparison: Secondary endpoint -- Incidence of asystolic pause \> 3 seconds for evaluable ITT population who had a primary event.p-value: 1Fisher Exact