Pragmatic Amiodarone Trial to Reduce Postoperative Atrial Fibrillation in Patients Undergoing Cardiac Surgery

Atrial Fibrillation Clinical Trial

— PATRONUS  

Official title:

Pragmatic Amiodarone Trial to Reduce Postoperative Atrial Fibrillation in Patients Undergoing Cardiac Surgery

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05543278
• Other study ID #: 2022P001732
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: February 1, 2024
• Est. completion date: December 2025

Study information

• Verified date: January 2024
• Source: Massachusetts General Hospital
• Contact: Asishana A Osho, MD, MPH
• Phone: 617-643-9745
• Email: asishana.osho[@]mgh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Postoperative atrial fibrillation is quite common after cardiac surgery with up to 1 in 3 patients experiencing this abnormal heart rhythm. Amiodarone, a medication commonly used to treat atrial fibrillation, has been previously shown to be an effective prophylactic agent at decreasing the occurrence of postoperative atrial fibrillation in patients who underwent coronary artery bypass surgery. However, despite many studies which have demonstrated its effectiveness, it has not been widely used due to the concern of side effects that can occur such as slow heart rate, low blood pressure, and lung toxicity. We have designed a study to test the effectiveness and safety of a short course of postoperative prophylactic amiodarone for patients undergoing non-coronary artery bypass cardiac surgery. We hypothesize that patients who receive the prophylactic amiodarone will have decreased rates of postoperative atrial fibrillation without significantly increased side effects compared to patients who receive the standard postoperative care after non-coronary artery bypass cardiac surgery.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 242
• Est. completion date: December 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• >= 18 years of age

• All genders

• All non-coronary artery bypass cardiac surgery patients

• Preoperative normal sinus rhythm

Exclusion Criteria:

• Pre-existing atrial fibrillation or atrial arrhythmias

• Pre-existing heart block

• Cardiogenic shock

• Sick sinus syndrome

• Marked sinus bradycardia

• Preoperative amiodarone use

• Contraindication to amiodarone use

• PR interval > 240 ms

• QTc > 550 ms

• 2nd or 3rd degree heart block

• Liver impairment (INR > 1.7, AST/ALT > 2x normal)

• Uncontrolled hyperthyroidism or hypothyroidism

• Interstitial lung disease

• Pregnancy and/or breastfeeding

• Known hypersensitivity to any components of amiodarone, including iodine

• Emergent operation

• Planned MAZE or Pulmonary Vein Isolation procedure

Related Conditions & MeSH terms

• Atrial Fibrillation
• Surgery, Cardiac

Intervention

Drug:
• Amiodarone
Patients randomized to the Amiodarone Arm will receive a 5-day course of amiodarone after surgery.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

References & Publications (8)

Arsenault KA, Yusuf AM, Crystal E, Healey JS, Morillo CA, Nair GM, Whitlock RP. Interventions for preventing post-operative atrial fibrillation in patients undergoing heart surgery. Cochrane Database Syst Rev. 2013 Jan 31;2013(1):CD003611. doi: 10.1002/14651858.CD003611.pub3. — View Citation

Buckley MS, Nolan PE Jr, Slack MK, Tisdale JE, Hilleman DE, Copeland JG. Amiodarone prophylaxis for atrial fibrillation after cardiac surgery: meta-analysis of dose response and timing of initiation. Pharmacotherapy. 2007 Mar;27(3):360-8. doi: 10.1592/phco.27.3.360. — View Citation

Chatterjee S, Sardar P, Mukherjee D, Lichstein E, Aikat S. Timing and route of amiodarone for prevention of postoperative atrial fibrillation after cardiac surgery: a network regression meta-analysis. Pacing Clin Electrophysiol. 2013 Aug;36(8):1017-23. doi: 10.1111/pace.12140. Epub 2013 Apr 29. — View Citation

Colunga Biancatelli RM, Congedo V, Calvosa L, Ciacciarelli M, Polidoro A, Iuliano L. Adverse reactions of Amiodarone. J Geriatr Cardiol. 2019 Jul;16(7):552-566. doi: 10.11909/j.issn.1671-5411.2019.07.004. — View Citation

Greenberg JW, Lancaster TS, Schuessler RB, Melby SJ. Postoperative atrial fibrillation following cardiac surgery: a persistent complication. Eur J Cardiothorac Surg. 2017 Oct 1;52(4):665-672. doi: 10.1093/ejcts/ezx039. — View Citation

Lawton JS, Tamis-Holland JE, Bangalore S, Bates ER, Beckie TM, Bischoff JM, Bittl JA, Cohen MG, DiMaio JM, Don CW, Fremes SE, Gaudino MF, Goldberger ZD, Grant MC, Jaswal JB, Kurlansky PA, Mehran R, Metkus TS Jr, Nnacheta LC, Rao SV, Sellke FW, Sharma G, Yong CM, Zwischenberger BA. 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 Jan 18;145(3):e18-e114. doi: 10.1161/CIR.0000000000001038. Epub 2021 Dec 9. No abstract available. Erratum In: Circulation. 2022 Mar 15;145(11):e772. — View Citation

Orr CF, Ahlskog JE. Frequency, characteristics, and risk factors for amiodarone neurotoxicity. Arch Neurol. 2009 Jul;66(7):865-9. doi: 10.1001/archneurol.2009.96. — View Citation

Wolkove N, Baltzan M. Amiodarone pulmonary toxicity. Can Respir J. 2009 Mar-Apr;16(2):43-8. doi: 10.1155/2009/282540. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Postoperative atrial fibrillation	The occurrence of postoperative atrial fibrillation detected by continuous telemetry, 12-lead electrocardiogram, and/or continuous ambulatory monitoring device through postoperative day 7.	At least 1 minute duration, occurring before or on postoperative day 7
Secondary	Operative mortality	Operative mortality as defined by either in-hospital death or death within 30 days of discharge.	Either in-hospital or within 30 days of procedure
Secondary	Stroke	characterized by deficits lasting > 24 hours and/or imaging findings of infarction	Either in-hospital or within 30 days of procedure
Secondary	Transient ischemic attack	characterized by examination findings lasting < 24 hours without associated imaging findings	Either in-hospital or within 30 days of procedure
Secondary	Electrical cardioversion	Whether the patient required electrical cardioversion for hemodynamically unstable atrial fibrillation	Either in-hospital or within 30 days of procedure
Secondary	Hemodynamic instability	New hemodynamic instability (mean arterial pressure < 65 mmHg) after surgery	Either in-hospital or within 30 days of procedure
Secondary	Initiation of systemic anticoagulation	New indication of systemic anticoagulation for stroke prophylaxis due to atrial fibrillation	Either in-hospital or within 30 days of procedure
Secondary	Myocardial infarction	Myocardial infarction diagnosed based on ECG and laboratory testing including pursued intervention and/or findings from subsequent angiography will be compared between intervention groups. To be considered a myocardial infarction, the diagnosis will have to be confirmed and documented in the chart by a board-certified cardiologist.	Either in-hospital or within 30 days of procedure
Secondary	Persistence of atrial fibrillation at discharge	Atrial fibrillation as diagnosed by final ECG	Up to 90 days
Secondary	Postoperative hospital length of stay	The postoperative length of stay will be calculated starting from the end of the procedure to time of discharge.	Up to 90 days
Secondary	Readmission	Rates of hospital readmission will be estimated for patients in each of the study intervention groups. Readmissions will be counted in this calculation if patients are admitted to the hospital. Emergency room visits without admission and outpatient visits will not count toward this calculation of readmission rates.	Within 30 days of procedure
Secondary	Symptomatic bradycardia	Symptomatic bradycardia (HR < 55 bpm) requiring intervention	Either in-hospital or within 30 days of procedure
Secondary	Number of patients with Amiodarone-related pulmonary toxicity	Clinical diagnosis of amiodarone-related pulmonary toxicity that uses a combination of x-ray findings consistent with known amiodarone-related pulmonary toxicity and clinical findings including shortness of breath, non-productive cough, and other diagnoses have been excluded.	Either in-hospital or within 30 days of procedure