Adenosine to Assess Complete Conduction Block During Catheter Ablation of Paroxysmal Atrial Fibrillation

Adenosine Study in Paroxysmal Atrial Fibrillation

The purpose of this study is to determine if additional ablation during the first procedure as the result of the ability to medically induce quiet atrial arrhythmias will improve clinical outcome in patients with atrial fibrillation thus decreasing the need for additional ablation procedures.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Adenosine; Drug: Isoproterenol

Detailed Description

Hypothesis:

1. Adenosine reveals incomplete conduction block due to partial tissue injury/stunning during catheter ablation of atrial fibrillation.
2. Identification of incomplete conduction block by adenosine improves clinical outcomes including an increase in efficacy and a decrease in need for repeat procedures after catheter ablation of atrial fibrillation.

Objectives:

1. In patients with paroxysmal Atrial Fibrillation (AF), the prevalence of Pulmonary Vein (PV) reconnection during adenosine infusion after complete PV isolation using conventional techniques will be determined.
2. Patients will be randomized to further ablation to achieve complete isolation during adenosine infusion vs to no further ablation.
3. Primary endpoint of the study will be freedom from any atrial arrhythmias 6 months after a single ablation procedure in the absence of antiarrhythmic drug therapy.
4. Secondary endpoints will include number of repeat ablation procedures because of documented recurrence of symptomatic AF or atrial flutter/tachycardia, outcome after 2 ablation procedures; Proportion of patients with AF or atrial flutter/tachycardia occuring during the first three months post ablation, prevalence of recovery of conduction into PVs during repeat ablation procedures in both groups, procedure duration, and incidence of peri-procedural complications including stroke, PV stenosis, cardiac perforation, atrio-esophageal fistulae, and death.

• Study Type: Interventional
• Enrollment (Actual): 131
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients >18 and <75 who are able to give informed consent undergoing atrial fibrillation ablation procedure.
2. Paroxysmal Atrial fibrillation lasting = 7 days which is self-terminating. It is considered recurrent if two or more episodes occur.
3. Failure or unwilling to take class I or III anti-arrhythmic drugs

Exclusion Criteria:

1. History of asthma
2. Patients with severe coronary artery disease, stable/unstable angina, or ongoing myocardial ischemia
3. Previous cardiac surgery ( excluding CABG and mitral valve surgery)
4. Symptomatic congestive heart failure including but not limited to NYHA III/IV and/or documented ejection fraction <40% measured by acceptable cardiac testing,
5. Left atrial diameter >55mm
6. Moderate to severe mitral or aortic valve disease
7. Myocardial infarction within three months of enrollment
8. Congenital heart disease where it increases the risk of an ablative procedure
9. Prior ASD/PFO closure with a device using a percutaneous approach
10. Hypertrophic cardiomyopathy (LV wall thickness >1.5mm)
11. Pulmonary Hypertension (mean or systolic PA pressure> 50mmHg on Doppler echocardiography
12. Any prior ablation of atrial fibrillation
13. Enrollment in any other arrhythmia protocol
14. Any ventricular arrhythmia being treated where the arrhythmia or management may interfere with this study
15. Active infection or sepsis
16. Any history of cerebrovascular disease including stroke or TIAs
17. Pregnancy or lactation
18. Left atrial thrombus at the time of ablation
19. Untreatable allergy to contrast media
20. Any diagnosis of atrial fibrillation secondary to electrolyte disturbance, thyroid disease, or any other reversible or non-cardiovascular causes
21. History of blood clotting(bleeding or thrombotic) abnormalities
22. Known sensitivities to heparin or warfarin
23. Severe COPD (defined as FEV1 <1)
24. Severe comorbidity or poor general physical/mental health that, in opinion of the investigator, will not allow the patient to be a good study candidate (i.e. other disease processes, mental capacity, substance abuse, shortened life expectancy)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adenosine and Isoproterenol; Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction.	Drug: Adenosine; Subject will receive 6-24 mg of intravenous adenosine given rapidly for each PV in order to assess dormant PV conduction. Subjects in this group will also receive isoproterenol to assess inducibility of AF with re-isolation of PVs and targeting non PV sources of AF if necessary.Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate.; Drug: Isoproterenol; Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to<85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.; Other Names: Isuprel
Other: Isoproterenol; This group will not receive adenosine during the procedure.	Drug: Isoproterenol; Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to<85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.; Other Names: Isuprel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freedom From Any Atrial Arrhythmias	Primary endpoint of the study will be number of participants who are free from any atrial arrhythmias after a single ablation procedure in the absence of antiarrhythmic drug therapy	2- 14 months after Ablation procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Who Need Repeat Ablations	Number of participants who had one or more repeat ablation procedures due to documented recurrence of Symptomatic AF or atrial flutter/tachycardia.	date of ablation to 6 months after procedure
Number of Subjects With AF or Atrial Flutter/Tachycardia Occurring During the First Three Months Post Ablation		first three months post ablation
Number of Pulmonary Veins That Recovered Conduction During Repeat Ablation Procedures in Both Groups	Prevalence of recovery of conduction into pulmonary veins during repeat ablation procedures in both groups. This is determined by surgeon assessment using a circular mapping catheter to identify recovery of conduction into the pulmonary veins.	post-procedure (6 months)
Incidence of Stroke	Number of subjects who develop stroke within 30 days after procedure.	peri-procedural (0 to 30 days after procedure)
Incidence of Pulmonary Vein Stenosis	Number of subjects who develop Symptomatic pulmonary vein stenosis	6 months post-procedure
Incidence of Cardiac Perforation	Number of subjects who develop perforation of heart during ablation	within 24 hours
Incidence of Atrio-esophageal Fistula	Number of subjects who develop connection between heart and the esophagus	within 4 weeks
Incidence of Death	Number of deaths within 90 days of the procedure.	with 90 days of the procedure

Collaborators and Investigators

• Sponsor: University of Michigan
• Investigators: Principal Investigator: Hamid Ghanbari, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: September 1, 2016
• First Submitted That Met QC Criteria: January 23, 2017
• First Posted (Estimate): January 26, 2017

Study Record Updates

• Last Update Posted (Actual): December 13, 2017
• Last Update Submitted That Met QC Criteria: November 15, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: atrial fibrillation; ablation; adenosine
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Purinergic Agents; Protective Agents; Adrenergic Agonists; Cardiotonic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-Agonists; Sympathomimetics; Purinergic P1 Receptor Agonists; Purinergic Agonists; Adenosine; Isoproterenol
• Other Study ID Numbers: HUM00048922