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

NCT05169866 | Recruiting Phase 3 DMC

• 1 other identifier: 2021-15
• Study Type: interventional
• Target: 274
• Locations: 1 country
• Sites: 1

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.

Conditions

New Onset Atrial Fibrillation; Complications; Cardiac, Postoperative

Keywords

Nifekalant; Amiodarone; Cardiac Surgery; Postoperative Atrial Fibrillation

Outcome Measures

Primary Outcomes (1)

• 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.

  4 hours

Secondary Outcomes (14)

• Rate of cardioversion at 90 minutes

  90 minutes

• Rate of cardioversion at 24 hours

  24 hours

• Maintenance time of sinus rhythm within 24 hours

  24 hours

• Average time to AF conversion to sinus rhythm

  24 hours

• The incidence of hypotension

  24 hours

Study Arms (2)

Intravenous Nifekalant

EXPERIMENTAL

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.

Drug: Nifekalant

Intravenous Amiodarone

ACTIVE COMPARATOR

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.

Drug: Amiodarone

Interventions

Nifekalant DRUG

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.

Also known as: Nifekalant Hydrochloride

Intravenous Nifekalant

Amiodarone DRUG

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.

Also known as: Amiodarone Hydrochloride

Intravenous Amiodarone

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Beijing Anzhen Hospital: lead

Study Sites (1)

Beijing Anzhen Hospital

Beijing, China

RECRUITING

MeSH Terms

Interventions

nifekalant; Amiodarone

Intervention Hierarchy (Ancestors)

Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Xiaotong Hou, MD, PhD

  Beijing Anzhen Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaotong Hou, MD, PhD

CONTACT

+8610 64456631; xt.hou@ccmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 29, 2021
• First Posted: December 27, 2021
• Study Start: May 29, 2022
• Primary Completion: May 1, 2025
• Study Completion: June 1, 2025
• Last Updated: June 3, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)