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

Primary Purpose

Ventricular Premature Complexes, Outflow Tract, Carvedilol

Status
Unknown status
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Carvedilol
Flecainide
Sponsored by
Keimyung University Dongsan Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ventricular Premature Complexes focused on measuring carvedilol, SOICR, triggered activity, outflow tract PVC/VT

Eligibility Criteria

19 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Keimyung University Dongsan Medical CenterRecruiting
  • Division of Cardiology, Department of Internal Medicine, Kyungpook National University HospitalRecruiting
  • Division of Cardiology, Department of Internal Medicine, Yeungnam University HospitalRecruiting
  • Division of Cardiology, Department of Internal Medicine, Daegu Catholic University Medical CenterRecruiting
  • Chonnam National University HospitalRecruiting
  • Korea University Anam HospitalRecruiting
  • Seoul National University HospitalRecruiting
  • Severance Cardiovascular HospitalRecruiting
  • Seoul Asan Medical CenterRecruiting
  • Seoul Samsung Medical CenterRecruiting
  • Seoul St. Mary's HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Carvedilol group

Flecainide group

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

PVC burden
Percentage of PVC/VT beat out of 24 hour total heart beat in Holter monitoring

Secondary Outcome Measures

Symptom assessment scale
questionnaire for PVC/VT symptoms using symptom assessment scale (Min 0 to Max 100)
Side effect of drugs
Difference in occurrence of side effects of each drug

Full Information

First Posted
July 2, 2018
Last Updated
July 16, 2018
Sponsor
Keimyung University Dongsan Medical Center
Collaborators
Chong Kun Dang Pharmaceutical Corp.
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1. Study Identification

Unique Protocol Identification Number
NCT03587558
Brief Title
Effects of Carvedilol on Suppressing the Premature Ventricular Complex/Ventricular Tachycardia From Outflow Tract
Acronym
FOREVER
Official Title
Effects of Carvedilol on Suppressing the Premature Ventricular Complex/Ventricular Tachycardia From Outflow Tract
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Unknown status
Study Start Date
September 5, 2017 (Actual)
Primary Completion Date
December 31, 2019 (Anticipated)
Study Completion Date
December 31, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Keimyung University Dongsan Medical Center
Collaborators
Chong Kun Dang Pharmaceutical Corp.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ventricular Premature Complexes, Outflow Tract, Carvedilol
Keywords
carvedilol, SOICR, triggered activity, outflow tract PVC/VT

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
104 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Carvedilol group
Arm Type
Experimental
Arm Description
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.
Arm Title
Flecainide group
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Carvedilol
Other Intervention Name(s)
Dilatrend
Intervention Description
Patients in this group are taking carvedilol to inhibit outflow tract PVC/VT.
Intervention Type
Drug
Intervention Name(s)
Flecainide
Other Intervention Name(s)
Tambocor
Intervention Description
Patients in this group are taking flecainide to inhibit outflow tract PVC/VT.
Primary Outcome Measure Information:
Title
PVC burden
Description
Percentage of PVC/VT beat out of 24 hour total heart beat in Holter monitoring
Time Frame
3 months after reaching the maximum tolerated dose
Secondary Outcome Measure Information:
Title
Symptom assessment scale
Description
questionnaire for PVC/VT symptoms using symptom assessment scale (Min 0 to Max 100)
Time Frame
3 months after reaching the maximum tolerated dose
Title
Side effect of drugs
Description
Difference in occurrence of side effects of each drug
Time Frame
3 months after reaching the maximum tolerated dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jongmin Hwang, M.D., Ph.D.
Phone
+82-53-250-7333
Email
dsmcep@dsmc.or.kr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Seongwook Han, M.D., Ph.D.
Organizational Affiliation
Keimyung University Dongsan Medical Center
Official's Role
Study Chair
Facility Information:
Facility Name
Keimyung University Dongsan Medical Center
City
Daegu
ZIP/Postal Code
41931
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jongmin Hwang, M.D.
Phone
+82-53-250-7333
Email
dsmcep@dsmc.or.kr
First Name & Middle Initial & Last Name & Degree
Seongwook Han, MD, PhD
First Name & Middle Initial & Last Name & Degree
Yoon-Nyun Kim, MD, PhD
First Name & Middle Initial & Last Name & Degree
Hyoung-Seob Park, MD, PhD
First Name & Middle Initial & Last Name & Degree
Jongmin Hwang, MD, PhD
Facility Name
Division of Cardiology, Department of Internal Medicine, Kyungpook National University Hospital
City
Daegu
ZIP/Postal Code
41944
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Myung Hwan Bae, MD, PhD
Facility Name
Division of Cardiology, Department of Internal Medicine, Yeungnam University Hospital
City
Daegu
ZIP/Postal Code
42415
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dong Gu Shin, MD, PhD
Facility Name
Division of Cardiology, Department of Internal Medicine, Daegu Catholic University Medical Center
City
Daegu
ZIP/Postal Code
42472
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Young Soo Lee, MD, PhD
Facility Name
Chonnam National University Hospital
City
Gwangju
ZIP/Postal Code
61469
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hyung Wook Park, MD, PhD
Facility Name
Korea University Anam Hospital
City
Seoul
ZIP/Postal Code
02841
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jong-Il Choi, MD, PhD
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eue-Keun Choi, MD, PhD
Facility Name
Severance Cardiovascular Hospital
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Boyoung Joung, MD, PhD
Facility Name
Seoul Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jun Kim, MD, PhD
Facility Name
Seoul Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Young Keun On, MD, PhD
Facility Name
Seoul St. Mary's Hospital
City
Seoul
ZIP/Postal Code
06591
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sung-Hwan Kim

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified individual participant data for all primary and secondary outcome measures will be made available.
IPD Sharing Time Frame
Data will be available within 6 months of study completion.
IPD Sharing Access Criteria
Data access requests will be reviewed by an external independent Review Panel. Requestors will be required to sign a Data Access Agreement.

Learn more about this trial

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

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