Premature Ventricular ContractionTREAT-PVCNCT04909528
LLTS to Treat Premature Ventricular Contractions
A study testing Low-level tragus stimulation in people with Premature Ventricular Contraction, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
Trial summary
This randomized control trial is designed to explore the effect of low-level tragus stimulation in patients with frequent premature ventricular contractions. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Premature Ventricular Contraction
- What is being tested?
- Low-level tragus stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- 15 Mar 2021to 31 Dec 2022
- Phase
- Interventional
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >18, <80 of age
- Symptomatic PVCs refractory to ≥1 antiarrhythmic drugs (including β-blockers and calcium-channel blockers).
- PVC burden ≥ 10%, with or without prior ablation
- Arrhythmias originated from any focus (foci) in the right ventricular or left ventricular.
Who cannot join
- Left ventricular ejection fraction (LVEF) < 45% unless proven to be PVC-mediated cardiomyopathy (history of improving LVEF by >15% when PVC burden was reduced by pharmacological agents or ablation)
- EF continues to decrease in the past 4 months regardless of the etiology
- Unwilling to continue current pharmacological therapy during the study period
- Severe heart failure with New York Heart Association Class ≥ III
- Ventricular arrhythmias attributed to underlying structural heart disease, known myocardial scar or myocarditis
- Change of anti-arrhythmic drug dosing, including β-blockers and calcium channel blockers, within 2 months prior to enrollment
Show all 11Show fewer
- < 3 months after prior unsuccessful ablation:
- Patients on amiodarone
- Patients with known thyroid issues, on renal-dialysis
- life expectancy of < 12 months
- Sustained ventricular tachycardia
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
The First Affiliated Hospital of Nanjing Medical University
Nanjing, Jiangsu, 210000
Gang Yang, MD, 86-18601406982, yanggang201301@163.com
Chen minglong, MD
About this study
Official title: Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Premature Ventricular Contractions
This randomized control trial is designed to explore the effect of low-level tragus stimulation in patients with frequent premature ventricular contractions.
Read the detailed description
Background Premature ventricular contraction (PVC), also known as premature ventricular beat, is one of the most common symptomatic arrhythmias in clinical practice. PVCs may cause serious harm to patients as follow: 1. PVCs with considerable load can increase the incidence of cardiomyopathy; 2. Some recurrent malignant arrhythmias, such as ventricular tachycardia and ventricular fibrillation, can be induced by PVCs; 3. cardiac resynchronization therapy-pacing/defibrillator non-responders may be due to frequent PVCs, which reduce the proportion of biventricular pacing; 4. For structural heart disease patients, PVCs may make their damaged heart function further deteriorated. At present, the clinical treatment of PVCs is still based on drugs, such as beta-blockers, mexiletine, propafenone, etc., and their effectiveness varies greatly among individuals. The status of catheter ablation in the treatment of ventricular premature beats continuous improvement, but this is an invasive operation and relatively expensive, which limits its wide application in clinical practice. Recent studies have shown that the autonomic nervous system plays an important role in the occurrence and maintenance of ventricular arrhythmia. Relevant studies have confirmed that the onset of ventricular arrhythmia is related to sympathetic nerve excitement. Moreover, inhibiting sympathetic nerve activity, including anesthesia, sympathetic nerve block, sympathetic nerve denervation, etc., can effectively reduce the onset and burden of ventricular arrhythmia. On the other hand, in patients with myocardial ischemia-related ventricular arrhythmia, atrial arrhythmia, and heart failure, the safety and effectiveness of the treatment of vagus nerve stimulation have also been verified. Low-level tragus stimulation (LLTS) is an emerging method of regulating autonomic nerves. Functional cardiac magnetic resonance studies have confirmed that by stimulating the auricle branch of the vagus nerve distributed in the tragus of the outer ear, the central projection of the vagus nerve in the brainstem and other higher centers can be activated. It is worth noting that LLTS has been used in clinical practice to treat tinnitus and epilepsy. Moreover, recent studies have confirmed that LLTS can reduce sympathetic nerve activity, inhibit inflammatory factors, and reduce the atrial fibrillation burden in patients with paroxysmal atrial fibrillation.
Aim of the Study The current trial is designed to explore the effect of low-level tragus stimulation in patients with frequent premature ventricular contractions.
Study Design This is a randomized, prospective, parallel, single-blind multicenter design. The enrollment target for this investigation is 100 patients. Patients are randomized in a 1:1 fashion into one of the investigation arms: active and sham LLTS group. Active LLTSs are performed using a transcutaneous vagus nerve stimulation device (Parasym device, Parasym Health, London, United Kingdom) with an ear clip attached to the tragus of the right ear. In the sham group, the clips are attached to the ear lobe and regarded as effectless to vagus nerve. At baseline, 3 months, and 6 months, patients underwent noninvasive continuous ECG monitoring for 10 days to evaluate their PVC burden (defined as the percentage of premature ventricular beats in total heart beats) using an adhesive continuous ECG patch. Heart rate variability, quality of life, skin sympathetic nerve activity and serum cytokine measurement are evaluated at baseline and follow-up.
- Conditions
- Premature Ventricular Contraction
- Being tested
- Low-level tragus stimulation, Sham stimulation
- Keywords
- Premature Ventricular Contraction, Low-level Tragus Stimulation, autonomic nerve modulation
- Medical subject headings
- Ventricular Premature Complexes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low-level tragus stimulationDevice
Frequency: 20Hz; Pulse width: 0.2 ms; Current is based on the following: Determine the perception threshold (feeling tingling) at the time of baseline information assessment. Because of sensory adaptation, ask the patient 5 minutes later to increase the current by 1-5 mA. Try to find the current level below the discomfort level and above the perception threshold; Stimulation spot: ear tragus; Stimulation time: 30 min in the morning (from 6:00 a.m. to 9:00 a.m.) and 30 min in the evening (from 20:00 p.m. to 23:00 p.m.)
Sham stimulationDevice
Frequency: 20 Hz; Pulse width: 0.2 ms; Current is based on the following: Determine the perception threshold (feeling tingling) at the time of baseline information assessment. Because of sensory adaptation, ask the patient 5 minutes later to increase the current by 1-5 mA. Try to find the current level below the discomfort level and above the perception threshold; Stimulate spot: ear lobe. Stimulation time: 30 min in the morning (from 6:00 a.m. to 9:00 a.m.) and 30 min in the evening (from 20:00 p.m. to 23:00 p.m.)
| Study group | Role | What they receive |
|---|---|---|
| Experimental Group | Experimental | Low-level tragus stimulation Receives: Device: Low-level tragus stimulation |
| Control Group | Sham comparator | Sham stimulation Receives: Device: Sham stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
PVC burden
Patients underwent noninvasive continuous ECG monitoring using an adhesive continuous ECG patch for 10 days to evaluate their PVC burden which is defined as the percentage of premature ventricular beats in total heart beats.
Measured: 3 months follow-up
PVC burden
Patients underwent noninvasive continuous ECG monitoring using an adhesive continuous ECG patch for 10 days to evaluate their PVC burden which is defined as the percentage of premature ventricular beats in total heart beats.
Measured: 6 months follow-up
Secondary outcomes (7)
Questionnaire to score severity of symptoms and quality of life
Patients are required to complete 36-item short form health survey questionnaire to score severity of symptoms and quality of life. The scores ranges from 0-100. Higher scores mean healthier status.
Measured: 3 months and 6 months follow-up
Serum cytokine marker
hsCRP (mg/L) level in serum
Measured: 3 months and 6 months follow-up
Serum cytokine marker
Interleukin-6 (ng/mL) level in serum
Measured: 3 months and 6 months follow-up
Skin sympathetic nerve activity
20-min recording using our customized device. The electrical activity that can be measured on the surface of the skin originates from the heart, the muscle or nerve structures. Because the frequency content of nerve activity falls in a higher frequency range than that of the ECG and myopotential, it is possible to use high-pass or band-pass filtering to specifically isolate the skin sympathetic nerve activity. The unit of measure is µV.
Measured: 3 months and 6 months follow-up
Treatment compliance
acquire patients' stimulation diaries to assess compliance
Measured: 3 months and 6 months follow-up
Number of participants with adverse effects
Number of participants with pruritus, flush, pain at the stimulation cite
Measured: 3 months and 6 months follow-up
Heart rate variability
Parameters include Standard deviation of the NN (R-R) intervals, Low frequency/High frequency ratio et al. which reflect sympathovagal balance and are calculated according to holter recording
Measured: 3 months and 6 months follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2021
- Study start15 Mar 2021
- Primary completion31 Dec 2022 (estimated)
- Study completion31 Dec 2022 (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 Premature Ventricular ContractionStudies of the same condition, open and under way.
- More trials run by The First Affiliated Hospital with Nanjing Medical UniversityThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oklahoma, The Affiliated Hospital of Xuzhou Medical University, Wuxi No. 2 People's Hospital, The First People's Hospital of Changzhou, Second Affiliated Hospital of Nantong University, Affiliated Hospital of Nantong University, Geriatric Hospital of Nanjing Medical University, First Affiliated Hospital of Wannan Medical College, Jiangsu Taizhou People's Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04909528
- Sponsor's protocol ID
- 2020-SR-328
- Acronym
- TREAT-PVC
- Status last verified
- Aug 2022
- First submitted
- 19 May 2021
- Last updated
- 11 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Wu N, Cai C, Jiang Q, Li C, Guo H, Yang J, Shi L, Gu Z, Yang G, Cui C, Liu H, Liu W, Shen Y, Chen M, Po SS. Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Ventricular Premature Complexes (TREAT-PVC): A Randomized Clinical Trial. JACC Clin Electrophysiol. 2026 Jun;12(6):1260-1272. doi: 10.1016/j.jacep.2026.01.011. Epub 2026 Apr 26.
PubMed 42043358Cai C, Wu N, Yang G, Yang S, Liu W, Chen M, Po SS; TREAT PVC investigators. Transcutaneous electrical vagus nerve stimulation to suppress premature ventricular complexes (TREAT PVC): study protocol for a multi-center, double-blind, randomized controlled trial. Trials. 2023 Oct 23;24(1):683. doi: 10.1186/s13063-023-07713-2.
PubMed 37872628
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Premature Ventricular Contractions
- ClinicalTrials.gov ID
- NCT04909528
- Acronym / sponsor ID
- TREAT-PVC / 2020-SR-328
- Conditions
- Premature Ventricular Contraction
- Keywords
- Premature Ventricular Contraction, Low-level Tragus Stimulation, autonomic nerve modulation
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital with Nanjing Medical UniversityUniversity, hospital or other
- Collaborators
- University of Oklahoma, The Affiliated Hospital of Xuzhou Medical University, Wuxi No. 2 People's Hospital, The First People's Hospital of Changzhou, Second Affiliated Hospital of Nantong University, Affiliated Hospital of Nantong University, Geriatric Hospital of Nanjing Medical University, First Affiliated Hospital of Wannan Medical College, Jiangsu Taizhou People's Hospital
- Study start
- 15 Mar 2021 (actual)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 1 Jun 2021 (actual)
- 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.
This randomized control trial is designed to explore the effect of low-level tragus stimulation in patients with frequent premature ventricular contractions.
Detailed description
Background Premature ventricular contraction (PVC), also known as premature ventricular beat, is one of the most common symptomatic arrhythmias in clinical practice. PVCs may cause serious harm to patients as follow: 1. PVCs with considerable load can increase the incidence of cardiomyopathy; 2. Some recurrent malignant arrhythmias, such as ventricular tachycardia and ventricular fibrillation, can be induced by PVCs; 3. cardiac resynchronization therapy-pacing/defibrillator non-responders may be due to frequent PVCs, which reduce the proportion of biventricular pacing; 4. For structural heart disease patients, PVCs may make their damaged heart function further deteriorated. At present, the clinical treatment of PVCs is still based on drugs, such as beta-blockers, mexiletine, propafenone, etc., and their effectiveness varies greatly among individuals. The status of catheter ablation in the treatment of ventricular premature beats continuous improvement, but this is an invasive operation and relatively expensive, which limits its wide application in clinical practice. Recent studies have shown that the autonomic nervous system plays an important role in the occurrence and maintenance of ventricular arrhythmia. Relevant studies have confirmed that the onset of ventricular arrhythmia is related to sympathetic nerve excitement. Moreover, inhibiting sympathetic nerve activity, including anesthesia, sympathetic nerve block, sympathetic nerve denervation, etc., can effectively reduce the onset and burden of ventricular arrhythmia. On the other hand, in patients with myocardial ischemia-related ventricular arrhythmia, atrial arrhythmia, and heart failure, the safety and effectiveness of the treatment of vagus nerve stimulation have also been verified. Low-level tragus stimulation (LLTS) is an emerging method of regulating autonomic nerves. Functional cardiac magnetic resonance studies have confirmed that by stimulating the auricle branch of the vagus nerve distributed in the tragus of the outer ear, the central projection of the vagus nerve in the brainstem and other higher centers can be activated. It is worth noting that LLTS has been used in clinical practice to treat tinnitus and epilepsy. Moreover, recent studies have confirmed that LLTS can reduce sympathetic nerve activity, inhibit inflammatory factors, and reduce the atrial fibrillation burden in patients with paroxysmal atrial fibrillation.
Aim of the Study The current trial is designed to explore the effect of low-level tragus stimulation in patients with frequent premature ventricular contractions.
Study Design This is a randomized, prospective, parallel, single-blind multicenter design. The enrollment target for this investigation is 100 patients. Patients are randomized in a 1:1 fashion into one of the investigation arms: active and sham LLTS group. Active LLTSs are performed using a transcutaneous vagus nerve stimulation device (Parasym device, Parasym Health, London, United Kingdom) with an ear clip attached to the tragus of the right ear. In the sham group, the clips are attached to the ear lobe and regarded as effectless to vagus nerve. At baseline, 3 months, and 6 months, patients underwent noninvasive continuous ECG monitoring for 10 days to evaluate their PVC burden (defined as the percentage of premature ventricular beats in total heart beats) using an adhesive continuous ECG patch. Heart rate variability, quality of life, skin sympathetic nerve activity and serum cytokine measurement are evaluated at baseline and follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental Group | Experimental | Device: Low-level tragus stimulationLow-level tragus stimulation |
| Control Group | Sham comparator | Device: Sham stimulationSham stimulation |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age >18, <80 of age
- Symptomatic PVCs refractory to ≥1 antiarrhythmic drugs (including β-blockers and calcium-channel blockers).
- PVC burden ≥ 10%, with or without prior ablation
- Arrhythmias originated from any focus (foci) in the right ventricular or left ventricular.
Key exclusion criteria (11 listed)
- Left ventricular ejection fraction (LVEF) < 45% unless proven to be PVC-mediated cardiomyopathy (history of improving LVEF by >15% when PVC burden was reduced by pharmacological agents or ablation)
- EF continues to decrease in the past 4 months regardless of the etiology
- Unwilling to continue current pharmacological therapy during the study period
- Severe heart failure with New York Heart Association Class ≥ III
- Ventricular arrhythmias attributed to underlying structural heart disease, known myocardial scar or myocarditis
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 |
|---|---|---|
| Low-level tragus stimulationFrequency: 20Hz; Pulse width: 0.2 ms; Current is based on the following: Determine the perception threshold (feeling tingling) at the time of baseline information assessment. Because of sensory adaptation, ask the patient 5 minutes later to increase the current by 1-5 mA. Try to find the current level below the discomfort level and above the perception threshold; Stimulation spot: ear tragus; Stimulation time: 30 min in the morning (from 6:00 a.m. to 9:00 a.m.) and 30 min in the evening (from 20:00 p.m. to 23:00 p.m.) | Device | Experimental Group |
| Sham stimulationFrequency: 20 Hz; Pulse width: 0.2 ms; Current is based on the following: Determine the perception threshold (feeling tingling) at the time of baseline information assessment. Because of sensory adaptation, ask the patient 5 minutes later to increase the current by 1-5 mA. Try to find the current level below the discomfort level and above the perception threshold; Stimulate spot: ear lobe. Stimulation time: 30 min in the morning (from 6:00 a.m. to 9:00 a.m.) and 30 min in the evening (from 20:00 p.m. to 23:00 p.m.) | Device | Control Group |
Primary outcome
PVC burden
Time frame: 3 months follow-up
Patients underwent noninvasive continuous ECG monitoring using an adhesive continuous ECG patch for 10 days to evaluate their PVC burden which is defined as the percentage of premature ventricular beats in total heart beats.
PVC burden
Time frame: 6 months follow-up
Patients underwent noninvasive continuous ECG monitoring using an adhesive continuous ECG patch for 10 days to evaluate their PVC burden which is defined as the percentage of premature ventricular beats in total heart beats.
7 secondary outcomes
Questionnaire to score severity of symptoms and quality of life
Time frame: 3 months and 6 months follow-up
Serum cytokine marker
Time frame: 3 months and 6 months follow-up
Serum cytokine marker
Time frame: 3 months and 6 months follow-up
Skin sympathetic nerve activity
Time frame: 3 months and 6 months follow-up
Treatment compliance
Time frame: 3 months and 6 months follow-up
Number of participants with adverse effects
Time frame: 3 months and 6 months follow-up
Heart rate variability
Time frame: 3 months and 6 months follow-up
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2022.
- Derived from this study: PubMed 42043358Wu N, Cai C, Jiang Q, Li C, Guo H, Yang J, Shi L, Gu Z, Yang G, Cui C, Liu H, Liu W, Shen Y, Chen M, Po SS. Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Ventricular Premature Complexes (TREAT-PVC): A Randomized Clinical Trial. JACC Clin Electrophysiol. 2026 Jun;12(6):1260-1272. doi: 10.1016/j.jacep.2026.01.011. Epub 2026 Apr 26.
- Derived from this study: PubMed 37872628Cai C, Wu N, Yang G, Yang S, Liu W, Chen M, Po SS; TREAT PVC investigators. Transcutaneous electrical vagus nerve stimulation to suppress premature ventricular complexes (TREAT PVC): study protocol for a multi-center, double-blind, randomized controlled trial. Trials. 2023 Oct 23;24(1):683. doi: 10.1186/s13063-023-07713-2.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Low-level tragus stimulation in people with Premature Ventricular Contraction, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
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 11 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 11 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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.
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?
Contact Gang MD Yang (+8618601406982, yanggang201301@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PVC burden (time frame: 3 months follow-up). The study lists 2 primary outcomes in all. 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 NCT04909528, 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 11 Aug 2022.