Intraoperative Amiodarone to Prevent Atrial Fibrillation in Lung Transplant Patients

• Sponsor: University of Louisville (Other)
• Overall Status: Completed
• CT.gov ID: NCT03221764
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arm: 1
• Actual Duration (Months): 17.4
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation; Lung Transplant; Complications	Drug: Amiodarone with CoSeal; Device: CO2 driver	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Intra-Operative Application of Amiodarone Releasing Hydrogel to Prevent Postoperative Atrial Fibrillation in Patients Undergoing Lung Transplantation
• Actual Study Start Date: Oct 19, 2017
• Actual Primary Completion Date: Feb 1, 2019
• Actual Study Completion Date: Apr 1, 2019

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Post Operative Atrial Fibrillation [Patients will be monitored for up to one year following lung transplant]

   Patient that developed atrial fibrillation after undergoing lung transplantation

Secondary Outcome Measures

1. Atrial Fibrillation Requiring Intervention [From transplant to discharge from hospital, up to 1 year]

   Patients that underwent cardioversion or ablation due to post operative atrial fibrillation

2. Anti-Arrhythmic Medication at Discharge [1 year]

   Patients that required anti-arrhythmic medication at the time of discharge for post operative atrial fibrillation.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jewish Hospital	Louisville	Kentucky	United States	40202

Sponsors and Collaborators

• University of Louisville

Investigators

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

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Jun 26, 2020

More Information

Publications

None provided.

• Responsible Party: Victor Van Berkel, Assistant Professor, University of Louisville
• ClinicalTrials.gov Identifier: NCT03221764
• Other Study ID Numbers: 16.1213
• First Posted: Jul 19, 2017
• Last Update Posted: Jun 29, 2020
• Last Verified: Jun 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Additional relevant MeSH terms: Atrial Fibrillation; Amiodarone

Study Results

Participant Flow

Arm/Group Title	Study Group
Arm/Group Description	Patients undergoing who underwent application of an amiodarone containing hydrogel at the time of lung transplant.
Period Title: Overall Study
STARTED	20
COMPLETED	20
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Study Group
Arm/Group Description	Patients undergoing who underwent application of an amiodarone containing hydrogel at the time of lung transplant.
Overall Participants	20
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	64.6
Sex: Female, Male (Count of Participants)
Female	4 20%
Male	16 80%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
United States	20 100%
Previous Myocardial Infarction (Count of Participants)
Count of Participants [Participants]	4 20%
Previous Coronary Artery Bypass (Count of Participants)
Count of Participants [Participants]	1 5%
Previous Percutaneous Coronary Intervention (Count of Participants)
Count of Participants [Participants]	5 25%
Diabetes (Count of Participants)
Count of Participants [Participants]	4 20%
Hypertension (Count of Participants)
Count of Participants [Participants]	12 60%
Cerebrovascular Disease (Count of Participants)
Count of Participants [Participants]	2 10%
Smoking History (Count of Participants)
Count of Participants [Participants]	8 40%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	Patients undergoing who underwent application of an amiodarone containing hydrogel at the time of lung transplant.
Measure Participants	20
Count of Participants [Participants]	6 30%

2. Secondary Outcome

Title	Atrial Fibrillation Requiring Intervention
Description	Patients that underwent cardioversion or ablation due to post operative atrial fibrillation
Time Frame	From transplant to discharge from hospital, up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	Patients undergoing who underwent application of an amiodarone containing hydrogel at the time of lung transplant.
Measure Participants	20
Count of Participants [Participants]	3 15%

3. Secondary Outcome

Title	Anti-Arrhythmic Medication at Discharge
Description	Patients that required anti-arrhythmic medication at the time of discharge for post operative atrial fibrillation.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	Patients undergoing who underwent application of an amiodarone containing hydrogel at the time of lung transplant.
Measure Participants	20
Count of Participants [Participants]	4 20%

Adverse Events

Time Frame	1 Year
Arm/Group Title	Study Group
Arm/Group Description	Patients undergoing who underwent application of an amiodarone containing hydrogel at the time of lung transplant.
All Cause Mortality
	Study Group
	Affected / at Risk (%)	# Events
Total	1/20 (5%)
Serious Adverse Events
	Study Group
	Affected / at Risk (%)	# Events
Total	0/20 (0%)
Cardiac disorders
Bradycardia	0/20 (0%)	0
Other (Not Including Serious) Adverse Events
	Study Group
	Affected / at Risk (%)	# Events
Total	0/20 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.