Effects of Carvedilol on Suppressing the Premature Ventricular Complex/Ventricular Tachycardia From Outflow Tract

Ventricular Premature Complexes Clinical Trial

— FOREVER  

Official title:

Effects of Carvedilol on Suppressing the Premature Ventricular Complex/Ventricular Tachycardia From Outflow Tract

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03587558
• Other study ID #: 2017-07-022
• Status: Recruiting
• Phase: Phase 4
• Start date: September 5, 2017
• Est. completion date: December 31, 2020

Study information

• Verified date: June 2018
• Source: Keimyung University Dongsan Medical Center
• Contact: Jongmin Hwang, M.D., Ph.D.
• Phone: +82-53-250-7333
• Email: dsmcep[@]dsmc.or.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 104
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 80 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• Pregnant, trying to become pregnant or breast feeding

• History of bronchial asthma

• History of coronary arterial disease

Related Conditions & MeSH terms

• Carvedilol
• Outflow Tract
• Premature Birth
• Tachycardia
• Tachycardia, Ventricular
• Ventricular Premature Complexes

Intervention

Drug:
• Carvedilol
Patients in this group are taking carvedilol to inhibit outflow tract PVC/VT.
• Flecainide
Patients in this group are taking flecainide to inhibit outflow tract PVC/VT.

Locations

Country	Name	City	State
Korea, Republic of	Division of Cardiology, Department of Internal Medicine, Daegu Catholic University Medical Center	Daegu
Korea, Republic of	Division of Cardiology, Department of Internal Medicine, Kyungpook National University Hospital	Daegu
Korea, Republic of	Division of Cardiology, Department of Internal Medicine, Yeungnam University Hospital	Daegu
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Seoul Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul Samsung Medical Center	Seoul
Korea, Republic of	Seoul St. Mary's Hospital	Seoul
Korea, Republic of	Severance Cardiovascular Hospital	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Keimyung University Dongsan Medical Center	Chong Kun Dang Pharmaceutical Corp.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PVC burden	Percentage of PVC/VT beat out of 24 hour total heart beat in Holter monitoring	3 months after reaching the maximum tolerated dose
Secondary	Symptom assessment scale	questionnaire for PVC/VT symptoms using symptom assessment scale (Min 0 to Max 100)	3 months after reaching the maximum tolerated dose
Secondary	Side effect of drugs	Difference in occurrence of side effects of each drug	3 months after reaching the maximum tolerated dose