Clinical trial NCT03587558: Effects of Carvedilol on Suppressing the Premature Ventricular Complex/Ventricular Tachycardia From Outflow Tract
Official title: Effects of Carvedilol on Suppressing the Premature Ventricular Complex/Ventricular Tachycardia From Outflow Tract
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Ventricular Premature Complexes
Outflow Tract
Carvedilol
Keywords: carvedilol
SOICR
triggered activity
outflow tract PVC/VT
Lead sponsor: Keimyung University Dongsan Medical Center
Sponsor class: OTHER
Collaborators: name: Chong Kun Dang Pharmaceutical Corp.
First posted: 2018-07-16
Enrollment: 104
Sex: ALL
Minimum age (years): 19
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: PVC burden
timeFrame: 3 months after reaching the maximum tolerated dose
Secondary outcomes:
measure: Symptom assessment scale
timeFrame: 3 months after reaching the maximum tolerated dose
measure: Side effect of drugs
timeFrame: 3 months after reaching the maximum tolerated dose
Other outcomes:
Locations:
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Daegu
country: Korea, Republic of
facility: Division of Cardiology, Department of Internal Medicine, Kyungpook National University Hospital
city: Daegu
country: Korea, Republic of
facility: Division of Cardiology, Department of Internal Medicine, Yeungnam University Hospital
city: Daegu
country: Korea, Republic of
facility: Division of Cardiology, Department of Internal Medicine, Daegu Catholic University Medical Center
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Cardiovascular Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital
Study officials:
affiliation: Keimyung University Dongsan Medical Center
name: Seongwook Han, M.D., Ph.D.
role: STUDY_CHAIR
References: