Trial Outcomes & Findings for Adenosine to Assess Complete Conduction Block During Catheter Ablation of Paroxysmal Atrial Fibrillation (NCT NCT03032965)

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

131 participants

Primary outcome timeframe

2- 14 months after Ablation procedure

Results posted on

2017-12-13

Participant Flow

Two subjects were not randomized.

Participant milestones

Participant milestones
Measure	Adenosine and Isoproterenol Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction. 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. 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.	Isoproterenol This group will not receive adenosine during the procedure. 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.
Overall Study STARTED	61	68
Overall Study COMPLETED	61	68
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Adenosine and Isoproterenol n=61 Participants Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction. 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. 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.	Isoproterenol n=68 Participants This group will not receive adenosine during the procedure. 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.	Total n=129 Participants Total of all reporting groups
Age, Continuous	59.7 years STANDARD_DEVIATION 8.7 • n=5 Participants	58.9 years STANDARD_DEVIATION 10.7 • n=7 Participants	59.3 years STANDARD_DEVIATION 13.8 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	15 Participants n=7 Participants	39 Participants n=5 Participants
Sex: Female, Male Male	37 Participants n=5 Participants	53 Participants n=7 Participants	90 Participants n=5 Participants
Region of Enrollment United States	61 Participants n=5 Participants	68 Participants n=7 Participants	129 Participants n=5 Participants
Left ventricular ejection fraction	59.7 Percentage STANDARD_DEVIATION 5.4 • n=5 Participants	59.3 Percentage STANDARD_DEVIATION 5.6 • n=7 Participants	59.5 Percentage STANDARD_DEVIATION 7.8 • n=5 Participants
left atrial diameter	41.0 milli meters STANDARD_DEVIATION 5.3 • n=5 Participants	41.2 milli meters STANDARD_DEVIATION 6.4 • n=7 Participants	41.1 milli meters STANDARD_DEVIATION 8.3 • n=5 Participants
Hypertension	33 Participants n=5 Participants	28 Participants n=7 Participants	61 Participants n=5 Participants
Diabetes Mellitus	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Obstructive sleep apnea	15 Participants n=5 Participants	19 Participants n=7 Participants	34 Participants n=5 Participants
Cerebrovascular accident	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Repeat procedure	20 Participants n=5 Participants	23 Participants n=7 Participants	43 Participants n=5 Participants
CHADS2 Score ( Congestive heart failure, Hypertension, Age > 75 years, Diabetes Mellitus, Stroke	0.8 units on a scale STANDARD_DEVIATION 0.7 • n=5 Participants	0.7 units on a scale STANDARD_DEVIATION 0.7 • n=7 Participants	0.75 units on a scale STANDARD_DEVIATION 0.9 • n=5 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Adenosine and Isoproterenol n=61 Participants Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction. 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. 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.	Isoproterenol n=68 Participants This group will not receive adenosine during the procedure. 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.
Freedom From Any Atrial Arrhythmias	24 Participants	23 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Adenosine and Isoproterenol n=61 Participants Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction. 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. 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.	Isoproterenol n=68 Participants This group will not receive adenosine during the procedure. 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.
Number of Subjects Who Need Repeat Ablations	12 Participants	9 Participants

SECONDARY outcome

Timeframe: first three months post ablation

Population: This data was not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: post-procedure (6 months)

Population: Only 21 participants had repeat ablations; each participant has four pulmonary veins therefore the number of connections measured is based 4 x the number of participants

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.

Outcome measures

Outcome measures
Measure	Adenosine and Isoproterenol n=48 pulmonary veins Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction. 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. 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.	Isoproterenol n=36 pulmonary veins This group will not receive adenosine during the procedure. 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.
Number of Pulmonary Veins That Recovered Conduction During Repeat Ablation Procedures in Both Groups	29 pulmonary veins	28 pulmonary veins

SECONDARY outcome

Timeframe: peri-procedural (0 to 30 days after procedure)

Number of subjects who develop stroke within 30 days after procedure.

Outcome measures

Outcome measures
Measure	Adenosine and Isoproterenol n=61 Participants Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction. 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. 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.	Isoproterenol n=68 Participants This group will not receive adenosine during the procedure. 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.
Incidence of Stroke	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 6 months post-procedure

Number of subjects who develop Symptomatic pulmonary vein stenosis

Outcome measures

Outcome measures
Measure	Adenosine and Isoproterenol n=61 Participants Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction. 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. 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.	Isoproterenol n=68 Participants This group will not receive adenosine during the procedure. 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.
Incidence of Pulmonary Vein Stenosis	0 Participants	0 Participants

SECONDARY outcome

Timeframe: within 24 hours

Number of subjects who develop perforation of heart during ablation

Outcome measures

Outcome measures
Measure	Adenosine and Isoproterenol n=61 Participants Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction. 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. 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.	Isoproterenol n=68 Participants This group will not receive adenosine during the procedure. 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.
Incidence of Cardiac Perforation	0 Participants	0 Participants

SECONDARY outcome

Timeframe: within 4 weeks

Number of subjects who develop connection between heart and the esophagus

Outcome measures

Outcome measures
Measure	Adenosine and Isoproterenol n=61 Participants Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction. 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. 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.	Isoproterenol n=68 Participants This group will not receive adenosine during the procedure. 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.
Incidence of Atrio-esophageal Fistula	0 Participants	0 Participants

SECONDARY outcome

Timeframe: with 90 days of the procedure

Number of deaths within 90 days of the procedure.

Outcome measures

Outcome measures
Measure	Adenosine and Isoproterenol n=61 Participants Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction. 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. 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.	Isoproterenol n=68 Participants This group will not receive adenosine during the procedure. 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.
Incidence of Death	0 Participants	0 Participants

Adverse Events

Adenosine and Isoproterenol

Serious events: 4 serious events

Other events: 0 other events

Deaths: 0 deaths

Isoproterenol

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Adenosine and Isoproterenol n=61 participants at risk Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction. 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. 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.	Isoproterenol n=68 participants at risk This group will not receive adenosine during the procedure. 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.
Vascular disorders Site hematoma	3.3% 2/61 • within 24 hours of procedure	2.9% 2/68 • within 24 hours of procedure
Vascular disorders Pericardial Effusion	1.6% 1/61 • within 24 hours of procedure	0.00% 0/68 • within 24 hours of procedure
Vascular disorders A V Fistula	1.6% 1/61 • within 24 hours of procedure	0.00% 0/68 • within 24 hours of procedure
Respiratory, thoracic and mediastinal disorders Transient phrenic nerve paralysis	0.00% 0/61 • within 24 hours of procedure	1.5% 1/68 • within 24 hours of procedure

Other adverse events

Adverse event data not reported

Additional Information

Hamid Ghanbari

University of Michigan

Phone: 734-963-7141

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place