Ventricular Premature ComplexesPhase 4FOREVERNCT03587558
Effects of Carvedilol on Suppressing the Premature Ventricular Complex/Ventricular Tachycardia From Outflow Tract
A Phase 4 study testing Carvedilol and Flecainide in people with Ventricular Premature Complexes and Outflow Tract, run by Keimyung University Dongsan Medical Center at 11 sites in South Korea.
Trial summary
Carvedilol is known to be effective in reducing ventricular arrhythmias and mortality in patients with heart failure. It is suggested that one of the mechanisms is its ability to block store overload-induced Calcium release which activates spontaneous calcium release by Ryanodine receptors. Read more about this study
- Who is it for?
- Ages 19 to 80 years
- Conditions the study is for
- Ventricular Premature Complexes, Outflow Tract, Carvedilol
- What is being tested?
- Carvedilol and Flecainide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 104 participants
- Where
- 11 sitesSouth Korea
- Study dates
- 5 Sep 2017to 31 Dec 2020
- 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 19 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with ventricular premature complexes/ventricular tachycardias originating from ventricular outflow tract confirmed on the 12-lead surface ECG
- Patients with PVC burden of 5% or more in 24-hour Holter monitoring
- Patients with normal left ventricular function
- left ventricular ejection fraction ≥50%
- Patients without structural heart disease
Who cannot join
- Pregnant, trying to become pregnant or breast feeding
- History of bronchial asthma
- History of coronary arterial disease
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
South Korea11 sites, 11 recruiting
- Recruiting
Keimyung University Dongsan Medical Center
Daegu, 41931
Jongmin Hwang, M.D., +82-53-250-7333, dsmcep@dsmc.or.kr
Seongwook Han, MD, PhD
- Recruiting
Division of Cardiology, Department of Internal Medicine, Kyungpook National University Hospital
Daegu, 41944
Myung Hwan Bae, MD, PhD
- Recruiting
Division of Cardiology, Department of Internal Medicine, Yeungnam University Hospital
Daegu, 42415
Dong Gu Shin, MD, PhD
- Recruiting
Division of Cardiology, Department of Internal Medicine, Daegu Catholic University Medical Center
Daegu, 42472
Young Soo Lee, MD, PhD
- Recruiting
Chonnam National University Hospital
Gwangju, 61469
Hyung Wook Park, MD, PhD
- Recruiting
Korea University Anam Hospital
Seoul, 02841
Jong-Il Choi, MD, PhD
- Recruiting
Seoul National University Hospital
Seoul, 03080
Eue-Keun Choi, MD, PhD
- Recruiting
Severance Cardiovascular Hospital
Seoul, 03722
Boyoung Joung, MD, PhD
- Recruiting
Seoul Asan Medical Center
Seoul, 05505
Jun Kim, MD, PhD
- Recruiting
Seoul Samsung Medical Center
Seoul, 06351
Young Keun On, MD, PhD
- Recruiting
Seoul St. Mary's Hospital
Seoul, 06591
Sung-Hwan Kim
About this study
Carvedilol is known to be effective in reducing ventricular arrhythmias and mortality in patients with heart failure. It is suggested that one of the mechanisms is its ability to block store overload-induced Calcium release which activates spontaneous calcium release by Ryanodine receptors. Ventricular outflow tract tachyarrhythmia is known to be associated with calcium overload due to activation of Ryanodine receptors. The aim of this study is to evaluate the efficacy of Carvedilol on premature ventricular complex(PVC)/ventricular tachycardia(VT) originating from outflow tract.
Read the detailed description
Carvedilol is one of the third-generation beta-blockers effective in reducing ventricular arrhythmias and mortality in patients with heart failure. Antioxidative and alpha - blocking effects, along with nonselective beta - blockade, have been described as a mechanism of effect in various diseases.
The antiarrhythmic effect of carvedilol inhibiting atrial fibrillation or ventricular arrhythmia has been reported, but its mechanism is not yet clear. Among them, inhibition of store overload-induced Ca2+ release (SOICR) is suggested as an antiarrhythmic mechanism of carvedilol.
Stimulation of the beta receptor leads to the entry of calcium into the sarcoplasmic reticulum (SR) by opening the L-type calcium channel. The influx of calcium through the L-type calcium channel also increases the calcium release through the Ryanodine receptor (RyR) in the sarcoplasmic reticulum. This is called Ca-induced Ca release and is known as a normal physiological response. However, when calcium overload in the myofibrillar body occurs, spontaneous calcium release, known as SOICR, can occur through RyR, which can make triggered activity by inducing Na+/Ca2+ exchanger present in myocardium, leading to severe arrhythmia. Among several beta-blockers, only carvedilol has been known as a drug that can directly inhibit SOICR in combination with beta-blockade effect.
Ventricular tachyarrhythmia originating from the ventricular outflow tract is an arrhythmia occurring in a patient with normal cardiac function. The mechanism of the arrhythmia is known to be triggered activity which is caused by activation of RyR due to increased cyclic adenosine monophasphate, resulting in calcium overload, eventually causing activation of Na+/Ca2+ exchanger. The aim of this study is to evaluate the efficacy of Carvedilol on PVC/VT originating from outflow tract.
- Conditions
- Ventricular Premature Complexes, Outflow Tract, Carvedilol
- Being tested
- Carvedilol, Flecainide
- Keywords
- carvedilol, SOICR, triggered activity, outflow tract PVC/VT
- 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.
CarvedilolDrug
Also called Dilatrend
Patients in this group are taking carvedilol to inhibit outflow tract PVC/VT.
FlecainideDrug
Also called Tambocor
Patients in this group are taking flecainide to inhibit outflow tract PVC/VT.
| Study group | Role | What they receive |
|---|---|---|
| Carvedilol group | Experimental | Patients in this group are taking carvedilol to inhibit outflow tract PVC/VT. Dilatrend® sustained release form of Chong Kun Dang Pharmaceutical will be used (initial dose: 8 mg sustained release form). Outpatient follow-up will be performed every 2 weeks and the dose is increased from the initial dose to a maximal tolerable dose, at the discretion of the investigator. Receives: Drug: Carvedilol |
| Flecainide group | Active comparator | Patients in this group are taking flecainide to inhibit outflow tract PVC/VT. Tambocor® of JW Pharmaceutical will be used. Outpatient follow-up will be performed every 2 weeks and the dose is increased from the initial dose to a maximal tolerable dose, at the discretion of the investigator. Receives: Drug: Flecainide |
What is being measured
The primary outcome is the main question the study is designed to answer.
PVC burden
Percentage of PVC/VT beat out of 24 hour total heart beat in Holter monitoring
Measured: 3 months after reaching the maximum tolerated dose
Secondary outcomes (2)
Symptom assessment scale
questionnaire for PVC/VT symptoms using symptom assessment scale (Min 0 to Max 100)
Measured: 3 months after reaching the maximum tolerated dose
Side effect of drugs
Difference in occurrence of side effects of each drug
Measured: 3 months after reaching the maximum tolerated dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2018
- Study start5 Sep 2017
- Primary completion31 Dec 2019 (estimated)
- Study completion31 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ventricular Premature ComplexesStudies 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
- None (open label)
- Enrolment
- 104 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Keimyung University Dongsan Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Chong Kun Dang Pharmaceutical Corp.
- Responsible party
- Sponsor
- Investigators
- Seongwook Han, M.D., Ph.D., Study chair, Keimyung University Dongsan Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03587558
- Sponsor's protocol ID
- 2017-07-022
- Acronym
- FOREVER
- Status last verified
- Jun 2018
- First submitted
- 2 Jul 2018
- Last updated
- 18 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data for all primary and secondary outcome measures will be made available.
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Carvedilol on Suppressing the Premature Ventricular Complex/Ventricular Tachycardia From Outflow Tract
- ClinicalTrials.gov ID
- NCT03587558
- Acronym / sponsor ID
- FOREVER / 2017-07-022
- Conditions
- Ventricular Premature Complexes, Outflow Tract, Carvedilol
- Keywords
- carvedilol, SOICR, triggered activity, outflow tract PVC/VT
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 104 participants (estimated)
- Lead sponsor
- Keimyung University Dongsan Medical CenterUniversity, hospital or other
- Collaborators
- Chong Kun Dang Pharmaceutical Corp.
- Study start
- 5 Sep 2017 (actual)
- Primary completion
- 31 Dec 2019 (estimated)
- Study completion
- 31 Dec 2020 (estimated)
- First posted
- 16 Jul 2018 (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.
Carvedilol is known to be effective in reducing ventricular arrhythmias and mortality in patients with heart failure. It is suggested that one of the mechanisms is its ability to block store overload-induced Calcium release which activates spontaneous calcium release by Ryanodine receptors. Ventricular outflow tract tachyarrhythmia is known to be associated with calcium overload due to activation of Ryanodine receptors. The aim of this study is to evaluate the efficacy of Carvedilol on premature ventricular complex(PVC)/ventricular tachycardia(VT) originating from outflow tract.
Detailed description
Carvedilol is one of the third-generation beta-blockers effective in reducing ventricular arrhythmias and mortality in patients with heart failure. Antioxidative and alpha - blocking effects, along with nonselective beta - blockade, have been described as a mechanism of effect in various diseases.
The antiarrhythmic effect of carvedilol inhibiting atrial fibrillation or ventricular arrhythmia has been reported, but its mechanism is not yet clear. Among them, inhibition of store overload-induced Ca2+ release (SOICR) is suggested as an antiarrhythmic mechanism of carvedilol.
Stimulation of the beta receptor leads to the entry of calcium into the sarcoplasmic reticulum (SR) by opening the L-type calcium channel. The influx of calcium through the L-type calcium channel also increases the calcium release through the Ryanodine receptor (RyR) in the sarcoplasmic reticulum. This is called Ca-induced Ca release and is known as a normal physiological response. However, when calcium overload in the myofibrillar body occurs, spontaneous calcium release, known as SOICR, can occur through RyR, which can make triggered activity by inducing Na+/Ca2+ exchanger present in myocardium, leading to severe arrhythmia. Among several beta-blockers, only carvedilol has been known as a drug that can directly inhibit SOICR in combination with beta-blockade effect.
Ventricular tachyarrhythmia originating from the ventricular outflow tract is an arrhythmia occurring in a patient with normal cardiac function. The mechanism of the arrhythmia is known to be triggered activity which is caused by activation of RyR due to increased cyclic adenosine monophasphate, resulting in calcium overload, eventually causing activation of Na+/Ca2+ exchanger. The aim of this study is to evaluate the efficacy of Carvedilol on PVC/VT originating from outflow tract.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Carvedilol group | Experimental | Drug: CarvedilolPatients in this group are taking carvedilol to inhibit outflow tract PVC/VT. Dilatrend® sustained release form of Chong Kun Dang Pharmaceutical will be used (initial dose: 8 mg sustained release form). Outpatient follow-up will be performed every 2 weeks and the dose is increased from the initial dose to a maximal tolerable dose, at the discretion of the investigator. |
| Flecainide group | Active comparator | Drug: FlecainidePatients in this group are taking flecainide to inhibit outflow tract PVC/VT. Tambocor® of JW Pharmaceutical will be used. Outpatient follow-up will be performed every 2 weeks and the dose is increased from the initial dose to a maximal tolerable dose, at the discretion of the investigator. |
Who may qualify
- Ages
- 19 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with ventricular premature complexes/ventricular tachycardias originating from ventricular outflow tract confirmed on the 12-lead surface ECG
- Patients with PVC burden of 5% or more in 24-hour Holter monitoring
- Patients with normal left ventricular function
- Patients without structural heart disease
Key exclusion criteria (3 listed)
- Pregnant, trying to become pregnant or breast feeding
- History of bronchial asthma
- History of coronary arterial disease
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 |
|---|---|---|
| CarvedilolAlso: DilatrendPatients in this group are taking carvedilol to inhibit outflow tract PVC/VT. | Drug | Carvedilol group |
| FlecainideAlso: TambocorPatients in this group are taking flecainide to inhibit outflow tract PVC/VT. | Drug | Flecainide group |
Primary outcome
PVC burden
Time frame: 3 months after reaching the maximum tolerated dose
Percentage of PVC/VT beat out of 24 hour total heart beat in Holter monitoring
2 secondary outcomes
Symptom assessment scale
Time frame: 3 months after reaching the maximum tolerated dose
Side effect of drugs
Time frame: 3 months after reaching the maximum tolerated dose
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2018.
- Individual participant dataSharing planned: Yes. De-identified individual participant data for all primary and secondary outcome measures will be made available.
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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.
Seongwook Han, M.D., Ph.D. study chair
Keimyung University Dongsan Medical Center
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Carvedilol and Flecainide in people with Ventricular Premature Complexes and Outflow Tract, run by Keimyung University Dongsan Medical Center at 11 sites in South Korea.
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 5 inclusion and 3 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 18 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in South Korea. 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. 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?
Contact Jongmin Hwang, M.D., Ph.D. (+82-53-250-7333, dsmcep@dsmc.or.kr), 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 after reaching the maximum tolerated dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Jul 2018.