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

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ClinicalTrials.gov Identifier: NCT03587558
Recruitment Status : Recruiting
First Posted : July 16, 2018
Last Update Posted : July 18, 2018
Sponsor:
Collaborator:
Chong Kun Dang Pharmaceutical Corp.
Information provided by (Responsible Party):
Keimyung University Dongsan Medical Center

Tracking Information
First Submitted Date  ICMJE July 2, 2018
First Posted Date  ICMJE July 16, 2018
Last Update Posted Date July 18, 2018
Actual Study Start Date  ICMJE September 5, 2017
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 2, 2018)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03587558 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2018)
  • Symptom assessment scale [ Time Frame: 3 months after reaching the maximum tolerated dose ]
    questionnaire for PVC/VT symptoms using symptom assessment scale (Min 0 to Max 100)
  • Side effect of drugs [ Time Frame: 3 months after reaching the maximum tolerated dose ]
    Difference in occurrence of side effects of each drug
Original Secondary Outcome Measures  ICMJE
 (submitted: July 2, 2018)
  • Symptom assessment scale [ Time Frame: 3 months after reaching the maximum tolerated dose ]
    questionnaire for PVC/VT symptoms using symptom assessment scale
  • Side effect of drugs [ Time Frame: 3 months after reaching the maximum tolerated dose ]
    Difference in occurrence of side effects of each drug
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of Carvedilol on Suppressing the Premature Ventricular Complex/Ventricular Tachycardia From Outflow Tract
Official Title  ICMJE Effects of Carvedilol on Suppressing the Premature Ventricular Complex/Ventricular Tachycardia From Outflow Tract
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Ventricular Premature Complexes
  • Outflow Tract
  • Carvedilol
Intervention  ICMJE
  • Drug: Carvedilol
    Patients in this group are taking carvedilol to inhibit outflow tract PVC/VT.
    Other Name: Dilatrend
  • Drug: Flecainide
    Patients in this group are taking flecainide to inhibit outflow tract PVC/VT.
    Other Name: Tambocor
Study Arms  ICMJE
  • Experimental: Carvedilol group
    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.
    Intervention: Drug: Carvedilol
  • Active Comparator: Flecainide group
    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: Drug: Flecainide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 2, 2018)
104
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2020
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 19 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jongmin Hwang, M.D., Ph.D. +82-53-250-7333 dsmcep@dsmc.or.kr
Listed Location Countries  ICMJE Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03587558
Other Study ID Numbers  ICMJE 2017-07-022
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data for all primary and secondary outcome measures will be made available.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: Analytic Code
Time Frame: Data will be available within 6 months of study completion.
Access Criteria: Data access requests will be reviewed by an external independent Review Panel. Requestors will be required to sign a Data Access Agreement.
Responsible Party Keimyung University Dongsan Medical Center
Study Sponsor  ICMJE Keimyung University Dongsan Medical Center
Collaborators  ICMJE Chong Kun Dang Pharmaceutical Corp.
Investigators  ICMJE
Study Chair: Seongwook Han, M.D., Ph.D. Keimyung University Dongsan Medical Center
PRS Account Keimyung University Dongsan Medical Center
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP