Blood Pressure, Ventricular Premature Complexes
Conditions
Brief summary
The purpose of this study is to determine if reduction in premature ventricular contraction (PVC) burden results in a decrease in blood pressure, sympathetic outflow, plasma catecholamines and an improvement in baroreflex gain. Flecainide will be used for PVC suppression in a randomized, double-blinded, crossover fashion.
Interventions
DRUGPVC Suppression using Flecainide
Flecainide will be administered to result in a reduction in PVC burden.
DRUGNo PVC Suppression using Placebo
Placebo (sugar pills) will be given to result in no alteration in PVC burden.
Sponsors
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Frequent symptomatic premature ventricular contractions (PVCs) (\>10% of total QRSs on a 24-hour Holter) * Willingness to participate in research
Exclusion criteria
* Age \> 65 years old * Pacemaker implantation * Implantable cardioverter defibrillator implantation requiring pacing * Sick sinus syndrome * Atrio-ventricular (AV) block * Left ventricular dysfunction defined as left ventricular ejection fraction \< 50% * History of myocardial infarction or coronary artery disease * Severe left ventricular hypertrophy (wall thickness \> 1.5 cm by echocardiography performed within 3 months from enrollment) * Severe liver dysfunction * Creatinine clearance of 35 mL/min/1.73 square meters or less * Pregnancy * Known hypersensitivity to the drug * QRS duration \> 120 ms * Recent change in blood pressure medication within 30 days of enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Arterial Pressure | Baseline and 28 days | Mean arterial blood pressure was calculated from non-invasive systolic and diastolic arm measurements. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Muscle Sympathetic Nerve Activity | Baseline and 28 days | Muscle sympathetic nerve activity was measured as number of bursts of neural activity per 100 heart beats. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Baroreflex Gain | Baseline and 28 days | Arterial baroreflex gain is calculated as slope of the relationship between cardiac cycle length and the corresponding change in systolic blood pressure. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PVC Suppression Then Placebo This arm will undergo attempted PVC suppression using flecainide for 28 days and then undergo no PVC suppression using placebo for 28 days.
PVC Suppression using Flecainide: Flecainide will be administered to result in a reduction in PVC burden.
No PVC Suppression using Placebo: Placebo (sugar pills) will be given to result in no alteration in PVC burden. | 4 |
| Placebo Then PVC Suppression This arm will undergo no PVC suppression using placebo for 28 days and then undergo attempted PVC suppression using flecainide for 28 days.
PVC Suppression using Flecainide: Flecainide will be administered to result in a reduction in PVC burden.
No PVC Suppression using Placebo: Placebo (sugar pills) will be given to result in no alteration in PVC burden. | 4 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | PVC Suppression Then Placebo | Placebo Then PVC Suppression | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 4 Participants | 8 Participants |
| PVC Burden | 26 % of heartbeats STANDARD_DEVIATION 13 | 30 % of heartbeats STANDARD_DEVIATION 13 | 28 % of heartbeats STANDARD_DEVIATION 12 |
| Sex: Female, Male Female | 4 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Male | 0 Participants | 4 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 3 | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 0 / 4 | 0 / 3 | 0 / 4 | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 3 | 0 / 4 | 0 / 4 |
Outcome results
Primary
Change in Mean Arterial Pressure
Mean arterial blood pressure was calculated from non-invasive systolic and diastolic arm measurements.
Time frame: Baseline and 28 days
Population: Mean arterial blood pressure values were not available at all time points for every patient. Data on subjects who completed the study is presented here and may not reflect changes seen in a larger population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Change From Base 1 to PVC Suppression | Change in Mean Arterial Pressure | 2 mmHg | Standard Deviation 2 |
| Change From Base 2 to no PVC Suppression | Change in Mean Arterial Pressure | 1 mmHg | Standard Deviation 4 |
| Change From Base 1 to no PVC Suppression | Change in Mean Arterial Pressure | 3 mmHg | Standard Deviation 11 |
| Change From Base 2 to PVC Suppression | Change in Mean Arterial Pressure | -4 mmHg | Standard Deviation 8 |
Secondary
Change in Muscle Sympathetic Nerve Activity
Muscle sympathetic nerve activity was measured as number of bursts of neural activity per 100 heart beats.
Time frame: Baseline and 28 days
Population: SNA values were not obtained in many of the participants in various groups above due to technical difficulties. Data on subjects who underwent the measurement are presented here and may not reflect changes seen in a larger population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Change From Base 1 to PVC Suppression | Change in Muscle Sympathetic Nerve Activity | 1 bursts / 100 heartbeats |
| Change From Base 2 to no PVC Suppression | Change in Muscle Sympathetic Nerve Activity | -10 bursts / 100 heartbeats |
| Change From Base 1 to no PVC Suppression | Change in Muscle Sympathetic Nerve Activity | -3 bursts / 100 heartbeats |
| Change From Base 2 to PVC Suppression | Change in Muscle Sympathetic Nerve Activity | 15 bursts / 100 heartbeats |
Other Pre-specified
Change in Baroreflex Gain
Arterial baroreflex gain is calculated as slope of the relationship between cardiac cycle length and the corresponding change in systolic blood pressure.
Time frame: Baseline and 28 days
Population: Arterial baroreflex gain values were not available at all time points. In one subject, gain could not be calculated because they were in bigeminy. Data on subjects who completed the study is presented here and may not reflect changes seen in a larger population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Change From Base 1 to PVC Suppression | Change in Baroreflex Gain | 4 ms/mmHg | Standard Deviation 1 |
| Change From Base 2 to no PVC Suppression | Change in Baroreflex Gain | 6 ms/mmHg | Standard Deviation 2 |
| Change From Base 1 to no PVC Suppression | Change in Baroreflex Gain | 8 ms/mmHg | Standard Deviation 5 |
| Change From Base 2 to PVC Suppression | Change in Baroreflex Gain | 15 ms/mmHg | Standard Deviation 7 |