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

• ClinicalTrials.gov Identifier: NCT03032965
• Recruitment Status: Completed
• First Posted: January 26, 2017
• Results First Posted: December 13, 2017
• Last Update Posted: December 13, 2017
• Sponsor: University of Michigan
• Information provided by (Responsible Party): Hamid Ghanbari, University of Michigan

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Atrial Fibrillation	Drug: Adenosine; Drug: Isoproterenol	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 131 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Adenosine Study in Paroxysmal Atrial Fibrillation
• Study Start Date: October 2011
• Actual Primary Completion Date: July 2015
• Actual Study Completion Date: July 2015

Arms and Interventions

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 Name: Isuprel
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 Name: Isuprel

Outcome Measures

Primary Outcome Measures :

1. Freedom From Any Atrial Arrhythmias [ Time Frame: 2- 14 months after Ablation procedure ]
   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

Secondary Outcome Measures :

1. Number of Subjects Who Need Repeat Ablations [ Time Frame: date of ablation to 6 months after procedure ]
   Number of participants who had one or more repeat ablation procedures due to documented recurrence of Symptomatic AF or atrial flutter/tachycardia.
2. Number of Subjects With AF or Atrial Flutter/Tachycardia Occurring During the First Three Months Post Ablation [ Time Frame: first three months post ablation ]
3. Number of Pulmonary Veins That Recovered Conduction During Repeat Ablation Procedures in Both Groups [ Time Frame: post-procedure (6 months) ]
   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.
4. Incidence of Stroke [ Time Frame: peri-procedural (0 to 30 days after procedure) ]
   Number of subjects who develop stroke within 30 days after procedure.
5. Incidence of Pulmonary Vein Stenosis [ Time Frame: 6 months post-procedure ]
   Number of subjects who develop Symptomatic pulmonary vein stenosis
6. Incidence of Cardiac Perforation [ Time Frame: within 24 hours ]
   Number of subjects who develop perforation of heart during ablation
7. Incidence of Atrio-esophageal Fistula [ Time Frame: within 4 weeks ]
   Number of subjects who develop connection between heart and the esophagus
8. Incidence of Death [ Time Frame: with 90 days of the procedure ]
   Number of deaths within 90 days of the procedure.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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)

Contacts and Locations

Locations

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

Sponsors and Collaborators

University of Michigan

Investigators

• Principal Investigator: Hamid Ghanbari, MD; University of Michigan

More Information

• Responsible Party: Hamid Ghanbari, Assistant Professor of Internal Medicine, University of Michigan
• ClinicalTrials.gov Identifier: NCT03032965
• Other Study ID Numbers: HUM00048922
• First Posted: January 26, 2017
• Results First Posted: December 13, 2017
• Last Update Posted: December 13, 2017
• Last Verified: November 2017

Keywords provided by Hamid Ghanbari, University of Michigan:

atrial fibrillation; ablation; adenosine

Additional relevant MeSH terms:

Atrial Fibrillation; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Adenosine; Isoproterenol; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Vasodilator Agents; Purinergic P1 Receptor Agonists; Purinergic Agonists; Purinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Bronchodilator Agents; Autonomic Agents; Anti-Asthmatic Agents; Respiratory System Agents; Cardiotonic Agents; Sympathomimetics; Protective Agents