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Nifekalant Versus Amiodarone in New-Onset Atrial Fibrillation After Cardiac Surgery

Primary Purpose

New Onset Atrial Fibrillation, Complications; Cardiac, Postoperative

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Nifekalant
Amiodarone
Sponsored by
Beijing Anzhen Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for New Onset Atrial Fibrillation focused on measuring Nifekalant, Amiodarone, Cardiac Surgery, Postoperative Atrial Fibrillation

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age ≥18 years old, <85 years old, no gender limit;
  2. Postoperative atrial fibrillation in the ICU after cardiac surgery;
  3. The duration of atrial fibrillation> 1 minute, and ≤ 48 hours;
  4. Hemodynamically stable (no need to increase vasoactive drugs and SBP>90/MAP>60mmHg);
  5. After pre-treatment (including: correcting electrolyte disturbances, optimizing volume status, improving oxygenation, controlling body temperature, analgesia and minimizing the use of inotropes and vasopressors), the clinician believes that antiarrhythmic drugs are needed.
  6. Obtained the informed consent from the patients or their family members.

Exclusion Criteria:

  1. Heart transplantation, left heart assist device (LVAD) or extracorporeal membrane oxygenation (ECMO) treatment;
  2. History of atrial fibrillation/atrial flutter and a history of paroxysmal supraventricular tachycardia;
  3. Radiofrequency ablation;
  4. Rheumatic heart disease;
  5. Complex congenital heart disease (with more than two coexisting congenital heart defects);
  6. Cardiac tumors;
  7. Transcatheter aortic valve implantation (TAVI), transcatheter mitral valve intervention (TMVI), and transcatheter tricuspid valve intervention (TTVI);
  8. Contraindications to amiodarone/nifekalant (PR interval>240ms; 2nd or 3rd degree atrioventricular block (AVB); QT>440ms; familial long QT syndrome; Untreated thyroid disease; AST or ALT>2 times the upper limit; liver cirrhosis; interstitial lung disease);
  9. Heart rate (HR) <50 beats/min and/or QRS>140ms without a pacemaker;
  10. Received amiodarone or nifekalant within 6 weeks before the operation;
  11. Pregnant and lactating female patients;
  12. Uncorrected hypokalemia (serum potassium <3.5mmol/L) or hypomagnesemia (whole blood/serum magnesium below the lower limit);
  13. Chronic renal failure and/or continuous renal replacement therapy (CRRT);
  14. Return to OR during ICU stay or readmission to ICU from Cardiac Surgery ward.
  15. Other factors not suitable for participating in this study

Sites / Locations

  • Beijing Anzhen HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Intravenous Nifekalant

Intravenous Amiodarone

Arm Description

Patients randomized to Nifekalant arm will receive a bolus of 0.3mg/kg IV in the first 5 minutes and a maintenance dose of 0.2-0.4mg/kg/h for 24 hours. If the patient has a recurrence of atrial fibrillation, the maintenance dose can be increased (up to 0.8 mg/kg/h) according to the patient's condition, or receive a bolus of 3mg/kg again at 2 hours intervals. Nifekalant is administered for 24 hours unless meeting the criteria for discontinuation.

Patients randomized to an amiodarone arm will receive a bolus of 150mg IV in the first 10 minutes and a maintenance dose of 0.5-1mg/min for 24 hours. If the patient has a recurrence of atrial fibrillation, the dosage can be adjusted according to the patient's condition, but the total dosage administered within 24 hours should not exceed 2g. Amiodarone is administered for 24 hours unless meeting the criteria for discontinuation.

Outcomes

Primary Outcome Measures

Rate of cardioversion at 4 hours
Rate of cardioversion of new-onset atrial fibrillation at 4 hours. The rate of cardioversion = the number of patients who meet the cardioversion criteria in the group / the total number of patients in the group × 100%. Cardioversion criteria is: atrial fibrillation stops at least once during the 24 hours observation period and lasts for more than 1 minute.

Secondary Outcome Measures

Rate of cardioversion at 90 minutes
Rate of cardioversion of new-onset atrial fibrillation at 90minutes. The rate of cardioversion = the number of cases who meet the cardioversion criteria in the group / the total number of cases in the group × 100%.
Rate of cardioversion at 24 hours
Rate of cardioversion of new-onset atrial fibrillation at 24 hours. The rate of cardioversion = the number of patients who meet the cardioversion criteria in the group / the total number of patients in the group × 100%.
Maintenance time of sinus rhythm within 24 hours
The total duration of sinus rhythm within 24 hours.
Average time to AF conversion to sinus rhythm
Average time from administration of drugs to cardioversion to sinus rhythm.
The incidence of hypotension
"Hypotension" is defined as: SBP <85mmHg for more than 5 minutes or increase of vasoactive drugs. Incidence = number of cases of hypotension / total number of cases in this group × 100%.
Vasoactive Inotropic Score (VIS) at 90 minutes, 4 hours, and 24 hours
VIS= Dopamine (ug/kg/min) + dobutamine (ug/kg/min) + 100×adrenaline (ug/kg/min) + 50×levosimendan (ug/kg/min) + 10× milrinone (ug/kg/min) + 10000× vasopressin (unit/kg/min) + 100×norepinephrine (ug/kg/min).
Incidence of severe bradycardia, 3rd degree AVB, severe ventricular arrhythmia
Severe ventricular arrhythmia: polymorphic/persistent ventricular tachycardia, torsade de pointes (Tdp), ventricular fibrillation. Incidence = number of cases of severe bradycardia, 3rd degree AVB, severe ventricular arrhythmia / total number of cases in this group × 100%.
Liver and kidney function within 24 hours
Indicators of liver function include ALT and AST. Indicator of kidney function is serum creatinine (Scr).
Cardiac function
Indicator of cardiac function is left ventricular ejection fraction (LVEF) assessed with echocardiography.
Adverse events
Adverse medical events that occur after a patient receives a drug, but it does not necessarily have a causal relationship with the treatment.
Co-administration of drugs
Including patients' basic medications and medications co-administrated during research.
Length of ICU stay
Days of patients' stay in ICU
Days of hospital stay
Days of patients' stay in hospital
Hospital mortality
Mortality of patients during hospitalization

Full Information

First Posted
November 29, 2021
Last Updated
August 5, 2023
Sponsor
Beijing Anzhen Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05169866
Brief Title
Nifekalant Versus Amiodarone in New-Onset Atrial Fibrillation After Cardiac Surgery
Official Title
A Randomized Active-Controlled Study Comparing Efficacy and Safety of Nifekalant to Amiodarone in New-Onset Atrial Fibrillation After Cardiac Surgery
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 29, 2022 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beijing Anzhen Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Postoperative atrial fibrillation is a major complication of cardiac surgery, which could lead to high morbidity and mortality, increase duration of hospital stay and increase the cost of treatment. New-onset atrial fibrillation after cardiac surgery is considered as a multifactorial phenomenon. Amiodarone, the most commonly used drug for cardioversion, is limited in atrial fibrillation after cardiac surgery due to side effects such as hypotension, bradycardia, and extracardiac side effects. Nifekalant is a novel class III antiarrhythmic agent with short onset time. It is a pure potassium channel blocker, which generally does not cause hypotension and bradycardia. There have been several trials that proven efficacy of nifekalant in converting persistent atrial fibrillation. For atrial fibrillation after cardiac surgery, the effectiveness and safety of nifekalant compared to amiodarone have not yet been reported. The investigators plan to perform a clinical trial comparing nifekalant to amiodarone in new-onset atrial fibrillation after cardiac surgery patients with a primary outcome of cardioversion at 4 hours. Secondary outcomes will follow cardioversion at 90 minutes and 24 hours, maintenance time of sinus rhythm within 24 hours, average time to conversion to sinus rhythm, rate of hypotension, length of ICU stay, length of hospital stay and hospital mortality.
Detailed Description
Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia post cardiac surgery. Estimates suggest that rates of patients experiencing AF after cardiac surgery exceeds 30%. AF has multiple effects on the cardiopulmonary hemodynamics. New-onset atrial fibrillation after cardiac surgery is considered as a multifactorial phenomenon. Its pathogenesis is characterized by inflammation, oxidative stress and autonomic dysfunction. AF after cardiac surgery could lead to high morbidity and mortality, increase duration of hospital stay and increase the cost of treatment. Treatment of AF include rhythm control and rate control. Typical rate control agents are contraindicated due to need of vasoactive requirements. The 2017 EACTS Guidelines on perioperative medication in adult cardiac surgery recommends that in patients with hemodynamically stable postoperative AF, rhythm control is recommended (I, B). Currently, amiodarone is most commonly used drug for rhythm control. It has long onset and cardioversion time. It can also cause side effects such as hypotension, typically requiring escalating doses of vasoactive medications. Other side effects include bradycardia, and extracardiac side effects in lung, liver and thyroid, which limit the clinical application of amiodarone in AF after cardiac surgery. Nifekalant is a novel class III antiarrhythmic agent with short onset time. It is a pure potassium channel blocker, which generally does not cause hypotension and bradycardia. Nifekalant prolongs the action potential duration and effective refractory period of atrial and ventricular myocytes, and prolong the QT interval. There have been several trials that proven efficacy of nifekalant in converting persistent atrial fibrillation. For new-onset AF post cardiac surgery, the effectiveness and safety of nifekalant compared to standard of care amiodarone have not yet been reported. Research hypothesis: For patients with new-onset atrial fibrillation after cardiac surgery, administration of nifekalant is not inferior to amiodarone in terms of rate of cardioversion to sinus rhythm at 4 hours. Methods: Patients after cardiac surgery will be recruited from the ICU based on inclusion and exclusion criteria. Patients identified with new-onset atrial fibrillation with a sustained duration of greater than 1 minutes and less than 48 hours will be considered for the study. Patients will be randomized to amiodarone versus nifekalant using a computerized process. The primary outcome is rate of cardioversion at 4 hours. Secondary outcomes include rates of cardioversion at 90 minutes and 24 hours, maintenance time of sinus rhythm within 24 hours, average time to cardioversion to sinus rhythm, rate of hypotension, length of ICU stay, length of hospital stay and hospital mortality.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
New Onset Atrial Fibrillation, Complications; Cardiac, Postoperative
Keywords
Nifekalant, Amiodarone, Cardiac Surgery, Postoperative Atrial Fibrillation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
274 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intravenous Nifekalant
Arm Type
Experimental
Arm Description
Patients randomized to Nifekalant arm will receive a bolus of 0.3mg/kg IV in the first 5 minutes and a maintenance dose of 0.2-0.4mg/kg/h for 24 hours. If the patient has a recurrence of atrial fibrillation, the maintenance dose can be increased (up to 0.8 mg/kg/h) according to the patient's condition, or receive a bolus of 3mg/kg again at 2 hours intervals. Nifekalant is administered for 24 hours unless meeting the criteria for discontinuation.
Arm Title
Intravenous Amiodarone
Arm Type
Active Comparator
Arm Description
Patients randomized to an amiodarone arm will receive a bolus of 150mg IV in the first 10 minutes and a maintenance dose of 0.5-1mg/min for 24 hours. If the patient has a recurrence of atrial fibrillation, the dosage can be adjusted according to the patient's condition, but the total dosage administered within 24 hours should not exceed 2g. Amiodarone is administered for 24 hours unless meeting the criteria for discontinuation.
Intervention Type
Drug
Intervention Name(s)
Nifekalant
Other Intervention Name(s)
Nifekalant Hydrochloride
Intervention Description
Patients identified with new-onset atrial fibrillation with a sustained duration of greater than 1 minutes and less than 48 hours will be considered for the study. Patients randomized to nifekalant arm will receive a bolus of 0.3mg/kg IV in the first 5 minutes and a maintenance dose of 0.2-0.4mg/kg/h for 24 hours.
Intervention Type
Drug
Intervention Name(s)
Amiodarone
Other Intervention Name(s)
Amiodarone Hydrochloride
Intervention Description
Patients identified with new-onset atrial fibrillation with a sustained duration of greater than 1 minutes and less than 48 hours will be considered for the study. Patients randomized to amiodarone arm will receive a bolus of 150mg IV in the first 10 minutes and a maintenance dose of 0.5-1mg/min for 24 hours.
Primary Outcome Measure Information:
Title
Rate of cardioversion at 4 hours
Description
Rate of cardioversion of new-onset atrial fibrillation at 4 hours. The rate of cardioversion = the number of patients who meet the cardioversion criteria in the group / the total number of patients in the group × 100%. Cardioversion criteria is: atrial fibrillation stops at least once during the 24 hours observation period and lasts for more than 1 minute.
Time Frame
4 hours
Secondary Outcome Measure Information:
Title
Rate of cardioversion at 90 minutes
Description
Rate of cardioversion of new-onset atrial fibrillation at 90minutes. The rate of cardioversion = the number of cases who meet the cardioversion criteria in the group / the total number of cases in the group × 100%.
Time Frame
90 minutes
Title
Rate of cardioversion at 24 hours
Description
Rate of cardioversion of new-onset atrial fibrillation at 24 hours. The rate of cardioversion = the number of patients who meet the cardioversion criteria in the group / the total number of patients in the group × 100%.
Time Frame
24 hours
Title
Maintenance time of sinus rhythm within 24 hours
Description
The total duration of sinus rhythm within 24 hours.
Time Frame
24 hours
Title
Average time to AF conversion to sinus rhythm
Description
Average time from administration of drugs to cardioversion to sinus rhythm.
Time Frame
24 hours
Title
The incidence of hypotension
Description
"Hypotension" is defined as: SBP <85mmHg for more than 5 minutes or increase of vasoactive drugs. Incidence = number of cases of hypotension / total number of cases in this group × 100%.
Time Frame
24 hours
Title
Vasoactive Inotropic Score (VIS) at 90 minutes, 4 hours, and 24 hours
Description
VIS= Dopamine (ug/kg/min) + dobutamine (ug/kg/min) + 100×adrenaline (ug/kg/min) + 50×levosimendan (ug/kg/min) + 10× milrinone (ug/kg/min) + 10000× vasopressin (unit/kg/min) + 100×norepinephrine (ug/kg/min).
Time Frame
24 hours
Title
Incidence of severe bradycardia, 3rd degree AVB, severe ventricular arrhythmia
Description
Severe ventricular arrhythmia: polymorphic/persistent ventricular tachycardia, torsade de pointes (Tdp), ventricular fibrillation. Incidence = number of cases of severe bradycardia, 3rd degree AVB, severe ventricular arrhythmia / total number of cases in this group × 100%.
Time Frame
24 hours
Title
Liver and kidney function within 24 hours
Description
Indicators of liver function include ALT and AST. Indicator of kidney function is serum creatinine (Scr).
Time Frame
24 hours
Title
Cardiac function
Description
Indicator of cardiac function is left ventricular ejection fraction (LVEF) assessed with echocardiography.
Time Frame
24 hours
Title
Adverse events
Description
Adverse medical events that occur after a patient receives a drug, but it does not necessarily have a causal relationship with the treatment.
Time Frame
24 hours
Title
Co-administration of drugs
Description
Including patients' basic medications and medications co-administrated during research.
Time Frame
24 hours
Title
Length of ICU stay
Description
Days of patients' stay in ICU
Time Frame
up to 6 months
Title
Days of hospital stay
Description
Days of patients' stay in hospital
Time Frame
up to 6 months
Title
Hospital mortality
Description
Mortality of patients during hospitalization
Time Frame
up to 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥18 years old, <85 years old, no gender limit; Postoperative atrial fibrillation in the ICU after cardiac surgery; The duration of atrial fibrillation> 1 minute, and ≤ 48 hours; Hemodynamically stable (no need to increase vasoactive drugs and SBP>90/MAP>60mmHg); After pre-treatment (including: correcting electrolyte disturbances, optimizing volume status, improving oxygenation, controlling body temperature, analgesia and minimizing the use of inotropes and vasopressors), the clinician believes that antiarrhythmic drugs are needed. Obtained the informed consent from the patients or their family members. Exclusion Criteria: Heart transplantation, left heart assist device (LVAD) or extracorporeal membrane oxygenation (ECMO) treatment; History of atrial fibrillation/atrial flutter and a history of paroxysmal supraventricular tachycardia; Radiofrequency ablation; Rheumatic heart disease; Complex congenital heart disease (with more than two coexisting congenital heart defects); Cardiac tumors; Transcatheter aortic valve implantation (TAVI), transcatheter mitral valve intervention (TMVI), and transcatheter tricuspid valve intervention (TTVI); Contraindications to amiodarone/nifekalant (PR interval>240ms; 2nd or 3rd degree atrioventricular block (AVB); QT>440ms; familial long QT syndrome; Untreated thyroid disease; AST or ALT>2 times the upper limit; liver cirrhosis; interstitial lung disease); Heart rate (HR) <50 beats/min and/or QRS>140ms without a pacemaker; Received amiodarone or nifekalant within 6 weeks before the operation; Pregnant and lactating female patients; Uncorrected hypokalemia (serum potassium <3.5mmol/L) or hypomagnesemia (whole blood/serum magnesium below the lower limit); Chronic renal failure and/or continuous renal replacement therapy (CRRT); Return to OR during ICU stay or readmission to ICU from Cardiac Surgery ward. Other factors not suitable for participating in this study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaotong Hou, MD, PhD
Phone
+8610 64456631
Email
xt.hou@ccmu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiaotong Hou, MD, PhD
Organizational Affiliation
Beijing Anzhen Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Anzhen Hospital
City
Beijing
State/Province
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaqiu Tian, phD
Phone
18813019563
Email
tianxiaqiu720@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Nifekalant Versus Amiodarone in New-Onset Atrial Fibrillation After Cardiac Surgery

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