Propafenone in the Treatment of Atrial Fibrillation

An Open-Label Randomized Study of Propafenone in the Treatment of Atrial Fibrillation

This is a open label randomized, multi-center study conducted in Taiwan. The study aims to evaluate the effectiveness and safety of oral Rhynorm (A drug) and Rytmonorm (B drug) for the conversion of paroxysmal AF and is designed to evaluate the improvement in sinus rhythm restoration after the treatment with Rhynorm (A drug) and Rytmonorm (B drug) for 24 weeks.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Propafenone

Detailed Description

This is a open label randomized, multi-center study conducted in Taiwan. The study aims to evaluate the effectiveness and safety of oral Rhynorm (A drug) and Rytmonorm (B drug) for the conversion of paroxysmal AF and is designed to evaluate the improvement in sinus rhythm restoration after the treatment with Rhynorm (A drug) and Rytmonorm (B drug) for 24 weeks.

This study comprised of three phases: a screening phase, a washout run-in qualifying phase lasting about 7 days, and a treatment phase of 24 weeks. A total of 60 evaluable subjects is planned to be enrolled. With an estimation of 20% dropout rate, 72 patients will be enrolled to reach 60 evaluable patients at the end of study. After screening for eligibility, the eligible subjects will be randomly assigned to either of the two gruop. The two-group are shown in the following table.

Group Treatment Drug Group A Rhynorm (A drug) Group B Rytmonorm (B drug) Patients with arrhythmia will be screened for eligibility after providing informed consent. Patients present with the symptoms of arrhythmia after withdrawn from other prohibited anti-AF agents for at least 7 days and completed run-in period event recorded will be qualified for entering this study and will be randomized to Rhynorm (A drug) treatment group or Rytmonorm (B drug) reference drud group in a 1:1 ratio.

The clinical evaluation will be recorded during the study period. Before treating with Rhynorm (A drug) and Rytmonorm (B drug), the physical examination and condition will be tracked and recorded for at least 7 days as the historical data.

During the treatment period, the subjects still had a routine OPD visit. Record symptom event and event recorder monitoring on OPD visit.

Safety assessments on all randomized subjects include adverse events, vital signs, and laboratory tests (hematology and biochemistry). Any adverse events, symptom events and concomitant medications/therapies will be recorded on the CRFs throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Kaohsiung, Taiwan
    • Kaohsiung Medical University Chung-Ho Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients who are 20~80 years of age
2. Recurrent AF patients
3. Patients with paroxysmal atrial fibrillation

4. Patients diagnosed with one of the ECG monitoring within 12 months prior screening visit:

   1. 12-lead electrocardiogram
   2. ECG used to make a 30 second one of recording
   3. 24 hours ECG (Holter Monitor)
   4. Long term ECG (Event Monitor)
5. Patient may be receiving stable dose of propafenone since at least 4 weeks prior screening visit.
6. Agree to and are able to follow the study procedures
7. Understand the nature of the study, and have signed informed consent forms

Exclusion Criteria:

1. Permanent or persistent AF

2. Any of the following heart disease:

   1. New York Heart Association class III or IV angina pectoris or heart failure
   2. previous electrocardiographic evidence of second- or third-degree atrioventricular block;
   3. Sinus node disease, AV conduction disturbance or bundle branch block in the absence of an artificial pacemaker
   4. Hemodynamic moderate valvular heart disease (stenosis and/or incompetent; regurgitation)
   5. Brugada syndrome
   6. Left ventricular EF< 50%
   7. Acute myocardial infarction or unstable angina within the previous 12 months
   8. Cardiogenic shock (excluding arrhythrmia shock) within the previous 12 months
   9. Acute pericarditis or myocarditis within the previous 6 months
   10. Cardiac or thoracic surgery within the previous 6 months
3. Symptomatic Bradycardia (heart rate less than 50 beats per minute)
4. Hemodynamic instability, defined as hypotension (SBP < 90 mm Hg)
5. Hyperthyroidism
6. Bronchospastic disorders or severe obstructive pulmonary disease
7. Correctable AF for other reasons
8. Marked electrolyte imbalance

9. Patients with clinically significant abnormalities in the following laboratory parameters:

   1. AST or ALT ≥ 3X upper limit of normal (ULN)
   2. Total bilirubin ≥ 2X ULN
   3. Creatinine ≥ 2.5 mg/dL
   4. Hemoglobin < 10 g/dL
   5. Platelet < 100,000/uL
10. Patients with known contraindication or history of allergy to Propafenone.
11. Female patients who are pregnant or lactating.
12. Female patients of child-bearing potentiality who do not agree to use an effective method of contraception during the study
13. Patients currently participating in any drug related clinical trial within 30 days
14. Patients with propagating factor (e.g. Alcohol Abuse induced AF)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A drug; Rhynorm(A drug)	Drug: Propafenone; oral, TID; Other Names: A drug: Rhynorm; B drug: Rytmonorm
Active Comparator: B drug; Rytmonorm (B drug)	Drug: Propafenone; oral, TID; Other Names: A drug: Rhynorm; B drug: Rytmonorm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of patients with recurrent AF	To compare the effect of Rhynorm (A drug) and Rytmonorm (B drug) over 24 weeks of treatment based on the proportion of patients with recurrent AF	24 weeks treatment

Collaborators and Investigators

• Sponsor: TSH Biopharm Corporation Limited

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2019
• Primary Completion (Actual): August 17, 2021
• Study Completion (Actual): August 17, 2021

Study Registration Dates

• First Submitted: September 14, 2018
• First Submitted That Met QC Criteria: September 14, 2018
• First Posted (Actual): September 17, 2018

Study Record Updates

• Last Update Posted (Actual): September 23, 2021
• Last Update Submitted That Met QC Criteria: September 22, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Membrane Transport Modulators; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Propafenone
• Other Study ID Numbers: TSHRH1801-P

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No