Intraoperative Amiodarone to Prevent Atrial Fibrillation in Lung Transplant Patients

The Intra-Operative Application of Amiodarone Releasing Hydrogel to Prevent Postoperative Atrial Fibrillation in Patients Undergoing Lung Transplantation

This study will prospectively evaluate the use of an amiodarone releasing hydrogel applied to the pulmonary veins and atria at the time of lung transplantation. This study will include patients undergoing lung transplantation at Jewish Hospital, Louisville KY. The prospective group will be compared to historical controls from the same institution. Investigators will access medical records and database entries for those patients undergoing lung transplantation after January 1st 2005 in order to obtain matched controls for analysis. Informed consent will be obtained from the prospective cohort prior to patient enrollment. This pilot study will be used to obtain preliminary data in order to proceed with a larger randomized control trial.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation; Lung Transplant; Complications
• Intervention / Treatment: Drug: Amiodarone with CoSeal; Device: CO2 driver

Detailed Description

Approximately 1900 transplants are performed in the US annually. Lung transplantation remains the gold standard treatment for patients with end stage lung disease. This includes patients with range of etiologies such as Idiopathic Pulmonary Fibrosis, COPD and Cystic Fibrosis. One of the more common post-operative complications in patients undergoing lung transplantation is the development of atrial fibrillation. Recent studies have demonstrated that approximately 1/3 of patients will develop atrial fibrillation during their post-operative course. While it is uncertain if the development of post-operative atrial fibrillation affects survival, it does significantly increase length of hospital stay. Importantly, a portion of the patients that develop atrial fibrillation post-operatively will require cardioversion prior to discharge.

Currently one of the main stays of treatment for post-operative atrial fibrillation is systemic (oral or intravenous) amiodarone, which is a class III antiarrhythmic agent. While this particular drug is effective, it does carry the risk of several known complications. Due to the drug's pharmacokinetics, amiodarone concentrates in organs with high lipid content such as the thyroid, liver and lung. Amiodarone has several known adverse effects on the lung ranging from acute respiratory distress syndrome to more chronic disease such as Interstitial pulmonary fibrosis. Amiodarone can have detrimental effects on the liver which in rare cases could lead to cirrhosis. Additionally, amiodarone can cause thyrotoxicosis as early as a few weeks after the initiation of amiodarone.

The adverse events listed above are related to the cumulative dose of amiodarone. Typically, when amiodarone is initiated, patients receive a loading dose of 600-800mg daily until the cumulative dose reaches 10 grams, after which patients will receive 200mg daily as a maintenance dose. Minimizing the cumulative dose of amiodarone by using a local application, could mitigate the potential adverse drug toxicities. In a previous study, the application of an amiodarone releasing hydrogel performed intraoperatively was shown to significantly decrease the rates of post-operative atrial fibrillation in patients undergoing coronary artery bypass. Currently for patients undergoing lung transplantation, there is not a safe and effective measure available to prevent post-operative atrial fibrillation.

The Investigators aim to study the intraoperative application of an amiodarone containing hydrogel for prevention of post-operative atrial fibrillation in lung transplant patients.

In patients undergoing lung transplantation, post-operative atrial fibrillation is common and leads to prolonged hospital course and increased healthcare expenditures. Amiodarone is a main stay of therapy for atrial fibrillation, however this drug does have potential serious complications when administered systemically. The local application of amiodarone, could potentially decrease the rates of atrial fibrillation, while avoiding the systemic complications. This has the potential to decrease length of stay and decrease additional procedures (ie. Cardioversion) in patients undergoing lung transplantation.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Jewish Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject or legal representative has signed Informed Consent Form (ICF)
• Undergoing lung transplant at the Jewish Hospital
• Age ≥ 18 years
• Subjects willing and able to comply with the follow up requirements of the study

Exclusion Criteria:

• Patients with previous history of atrial fibrillation.
• Patients with previously documented allergy or adverse reaction to amiodarone.
• Patients with previous ablation for atrial fibrillation
• Patients with an implantable pacemaker.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Amiodarone with CoSeal administered with CO2 driver; Lung Transplant Recipients who receive Intraoperative application of an Amiodarone containing hydrogel at the time of transplant.

Drug: Amiodarone with CoSeal; CoSeal Surgical Sealant (Baxter Healthcare) consist of 2 formulations of synthetic polyethylene glycols, a dilute hydrogen chloride solution along with a sodium phosphate/sodium carbonate solution. These separate solutions are mixed at the time of application to form a hydrogel. Amiodarone hydrochloride powder (1mg/kg) will be mixed with CoSeal at the time of application to form an amiodarone containing hydrogel. The dosing of amiodarone is based on previous study using amiodarone hydrogel in post-operative coronary artery bypass patients [8]. This hydrogel will be delivered utilizing a CO2 driver along the pulmonary vein and arterial anastomoses, and to the surface right and left atria.; Other Names: Amiodarone with CoSealadministered with CO2 driver; Device: CO2 driver; The amiodarone hydrogel will be delivered utilizing a CO2 driver along the pulmonary vein and arterial anastomoses, and to the surface right and left atria.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post Operative Atrial Fibrillation	Patient that developed atrial fibrillation after undergoing lung transplantation	Patients will be monitored for up to one year following lung transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Atrial Fibrillation Requiring Intervention	Patients that underwent cardioversion or ablation due to post operative atrial fibrillation	From transplant to discharge from hospital, up to 1 year
Anti-Arrhythmic Medication at Discharge	Patients that required anti-arrhythmic medication at the time of discharge for post operative atrial fibrillation.	1 year

Collaborators and Investigators

• Sponsor: University of Louisville
• Investigators: Principal Investigator: Victor H van Berkel, MD, PHD, University of Louisville

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2017
• Primary Completion (Actual): February 1, 2019
• Study Completion (Actual): April 1, 2019

Study Registration Dates

• First Submitted: July 10, 2017
• First Submitted That Met QC Criteria: July 17, 2017
• First Posted (Actual): July 19, 2017

Study Record Updates

• Last Update Posted (Actual): June 29, 2020
• Last Update Submitted That Met QC Criteria: June 26, 2020
• Last Verified: June 1, 2020

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; Vasodilator Agents; Enzyme Inhibitors; Membrane Transport Modulators; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Sodium Channel Blockers; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Potassium Channel Blockers; Amiodarone
• Other Study ID Numbers: 16.1213

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes