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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01HL124935-01A1 | U.S. NIH Grant/Contract | View source |
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Study halted/terminated prematurely due to COVID.
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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Propafenone is a currently used medicine to treat atrial fibrillation and is a mixture of two compounds, (R)-propafenone and (S)-propafenone. In this study, the investigators will randomize participants to (R)-propafenone, (S)-propafenone, or placebo.
Atrial fibrillation is a common cardiac arrhythmia that needs development of more effective medications. Propafenone is a medicine currently used to treat atrial fibrillation and is a mixture of two compounds, (R)-propafenone and (S)-propafenone. The investigators have discovered that purified (R)-propafenone may be more effective than (S)-propafenone for treatment of atrial fibrillation, and that (S)-propafenone reduces the efficacy of (R)-propafenone when administered as a mixture. This study will compare the ability of (R)-propafenone, (S)-propafenone, and placebo to suppress the induction of atrial fibrillation in participants undergoing an atrial fibrillation ablation procedure.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| (R)-propafenone | Experimental | Single intravenous dose of (R)-propafenone (2mg/kg) infused over 10 minutes |
|
| (S)-Propafenone | Active Comparator | Single intravenous dose of (S)-propafenone (2mg/kg) infused over 10 minutes |
|
| Placebo | Placebo Comparator | Placebo (normal saline) is infused over 10 minutes |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| (R)-propafenone | Drug |
| ||
| (S)-Propafenone |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Successful Induction of 30 Seconds of Atrial Fibrillation/Atrial Flutter | A rapid atrial pacing protocol was used to attempt to induce atrial fibrillation/atrial flutter. Twenty minutes after start of the study drug, participants underwent placement of a decapolar coronary sinus catheter. Pacing was performed from the proximal electrode at 20 milliamps and a pulse width of 2 ms. Bursts from the CS proximal electrode were induced to attempt atrial fibrillation. | Twenty minutes post-dosage to end of induction protocol (approximately 10 minutes) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Successful Inducibility of Atrial Fibrillation/Atrial Flutter Expressed as an Ordinal Variable Based on Stage of the Induction Protocol | Inducibility of atrial fibrillation (AF) or atrial flutter (AFL) expressed as an ordinal variable based on stage of the induction protocol.
Stage 3 consisted of 15-second bursts. The cycle length used for the bursts was the fastest cycle length achieved during Step 2 that maintained 1:1 atrial conduction. |
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Inclusion:
Exclusion:
Long-standing persistent atrial fibrillation at the time of ablation (greater than 1 year of a continuous atrial fibrillation episode)
Is in atrial fibrillation or atrial flutter the morning of the ablation procedure
The presence of any of the following in a patient without a permanent pacemaker for implantable cardiac defibrillator
Concomitant use of CYP3A4 and CYP2D6 inhibitors
Previous surgical or catheter ablation for atrial fibrillation or Cox-Maze procedure
Amiodarone use within 3 months prior to enrollment
Antiarrhythmic drug (other than amiodarone) within 5 half-lives prior to atrial fibrillation ablation
Expected life span < 1 year
Creatinine clearance <30 mL/min
Reversible cause of atrial fibrillation (ie. thyrotoxicosis)
Unrevascularized coronary artery disease
Canadian class IV angina
Left ventricular ejection fraction <40%
New York Heart Association Class III or IV symptoms
Previous heart transplantation
Planned heart transplantation or ventricular assist device
Cardiac/thoracic surgery <6 months prior to enrollment
Severe asthma or chronic obstructive pulmonary disease
Breastfeeding
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| Name | Affiliation | Role |
|---|---|---|
| Bjorn Knollmann, MD/PhD | Vanderbilt University | Principal Investigator |
| Ben Shoemaker, MD | Vanderbilt University | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanderbilt University | Nashville | Tennessee | 37232 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24493699 | Background | Faggioni M, Savio-Galimberti E, Venkataraman R, Hwang HS, Kannankeril PJ, Darbar D, Knollmann BC. Suppression of spontaneous ca elevations prevents atrial fibrillation in calsequestrin 2-null hearts. Circ Arrhythm Electrophysiol. 2014 Apr;7(2):313-20. doi: 10.1161/CIRCEP.113.000994. Epub 2014 Feb 3. | |
| 36166682 | Derived | Shoemaker MB, Yoneda ZT, Crawford DM, Akers WS, Richardson T, Montgomery JA, Phillips S, Shyr Y, Saavedra P, Estrada JC, Kanagasundram A, Shen ST, Michaud GF, Crossley G, Ellis CR, Knollmann BC. A Mechanistic Clinical Trial Using (R)- Versus (S)-Propafenone to Test RyR2 (Ryanodine Receptor) Inhibition for the Prevention of Atrial Fibrillation Induction. Circ Arrhythm Electrophysiol. 2022 Oct;15(10):e010713. doi: 10.1161/CIRCEP.121.010713. Epub 2022 Sep 27. |
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193 participants were enrolled. 1 participant withdrew consent prior to randomization.
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| ID | Title | Description |
|---|---|---|
| FG000 | (R)-Propafenone | Single intravenous dose of (R)-propafenone (1mg/kg) infused over 10 minutes (R)-propafenone |
| FG001 | (S)-Propafenone | Single intravenous dose of (S)-propafenone (1mg/kg) infused over 10 minutes (S)-Propafenone |
| FG002 | Placebo | Placebo (normal saline) is infused over 10 minutes Placebo |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
One participant was not randomized
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| ID | Title | Description |
|---|---|---|
| BG000 | (R)-Propafenone | Single intravenous dose of (R)-propafenone (1mg/kg) infused over 10 minutes (R)-propafenone |
| BG001 | (S)-Propafenone | Single intravenous dose of (S)-propafenone (1mg/kg) infused over 10 minutes (S)-Propafenone |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Successful Induction of 30 Seconds of Atrial Fibrillation/Atrial Flutter | A rapid atrial pacing protocol was used to attempt to induce atrial fibrillation/atrial flutter. Twenty minutes after start of the study drug, participants underwent placement of a decapolar coronary sinus catheter. Pacing was performed from the proximal electrode at 20 milliamps and a pulse width of 2 ms. Bursts from the CS proximal electrode were induced to attempt atrial fibrillation. | 27 Participants not analyzed as follows: R GROUP: (1) prolonged pharmacy time compounding the study med; (8) arrived in atrial fib/flutter; (1) physician withdrew due to PAC's; (1) took antiarrhythmic prior to ablation; (1) difficult anatomy (1) ischemia on MRI; (1) Due to COVID the lab halted elective research. S GROUP: (7) arrived in afib; (1) clot on TEE; (1) elevated anxiety in patient; (1) procedure scheduled late in day; (1) cardiac cath work-up needed. PLACEBO GROUP: (2) arrived in afib | Posted | Count of Participants | Participants | Twenty minutes post-dosage to end of induction protocol (approximately 10 minutes) |
|
Adverse event information was collected the day of procedure only
Adverse event information was collected for any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | (R)-Propafenone | Single intravenous dose of (R)-propafenone (1mg/kg) infused over 10 minutes (R)-propafenone |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Benjamin Shoemaker, MD | Vanderbilt University Medical Center | 615-322-2318 | moore.b.shoemaker@vumc.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 3, 2019 | Apr 12, 2021 | Prot_SAP_002.pdf |
| ICF | No | No | Yes | Informed Consent Form | Oct 23, 2019 | Jul 16, 2020 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D001281 | Atrial Fibrillation |
| ID | Term |
|---|---|
| D001145 | Arrhythmias, Cardiac |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D011405 | Propafenone |
| ID | Term |
|---|---|
| D011427 | Propiophenones |
| D007659 | Ketones |
| D009930 | Organic Chemicals |
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|
| Placebo | Drug |
|
| Twenty minutes post-dosage to end of induction protocol (approximately 10 minutes) |
| Number of Participants With Successful Induction of 30 Seconds of Atrial Flutter | A rapid atrial pacing protocol was used to attempt to induce atrial flutter. Twenty minutes after start of the study drug, participants underwent placement of a decapolar coronary sinus catheter. Pacing was performed from the proximal electrode at 20 milliamps and a pulse width of 2 ms. Bursts from the CS proximal electrode were induced to attempt atrial flutter. | Twenty minutes post-dosage to end of induction protocol (approximately 10 minutes) |
| arrived in afib/aflutter |
|
| BG002 | Placebo | Placebo (normal saline) is infused over 10 minutes Placebo |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG000 | (R)-Propafenone | Single intravenous dose of (R)-propafenone (1mg/kg) infused over 10 minutes (R)-propafenone |
| OG001 | (S)-Propafenone | Single intravenous dose of (S)-propafenone (1mg/kg) infused over 10 minutes (S)-Propafenone |
| OG002 | Placebo | Placebo (normal saline) is infused over 10 minutes Placebo |
|
|
| Secondary | Number of Participants With Successful Inducibility of Atrial Fibrillation/Atrial Flutter Expressed as an Ordinal Variable Based on Stage of the Induction Protocol | Inducibility of atrial fibrillation (AF) or atrial flutter (AFL) expressed as an ordinal variable based on stage of the induction protocol.
Stage 3 consisted of 15-second bursts. The cycle length used for the bursts was the fastest cycle length achieved during Step 2 that maintained 1:1 atrial conduction. | 27 Participants not analyzed as follows: R GROUP: (1) prolonged pharmacy time compounding the study med; (8) arrived in atrial fib/flutter; (1) physician withdrew due to PAC's; (1) took antiarrhythmic prior to ablation; (1) difficult anatomy (1) ischemia on MRI; (1) Due to COVID the lab halted elective research. S GROUP: (7) arrived in afib; (1) clot on TEE; (1) elevated anxiety in patient; (1) procedure scheduled late in day; (1) cardiac cath work-up needed. PLACEBO GROUP: (2) arrived in afib | Posted | Count of Participants | Participants | Twenty minutes post-dosage to end of induction protocol (approximately 10 minutes) |
|
|
|
| Secondary | Number of Participants With Successful Induction of 30 Seconds of Atrial Flutter | A rapid atrial pacing protocol was used to attempt to induce atrial flutter. Twenty minutes after start of the study drug, participants underwent placement of a decapolar coronary sinus catheter. Pacing was performed from the proximal electrode at 20 milliamps and a pulse width of 2 ms. Bursts from the CS proximal electrode were induced to attempt atrial flutter. | 27 Participants not analyzed as follows: R GROUP: (1) prolonged pharmacy time compounding the study med; (8) arrived in atrial fib/flutter; (1) physician withdrew due to PAC's; (1) took antiarrhythmic prior to ablation; (1) difficult anatomy (1) ischemia on MRI; (1) Due to COVID the lab halted elective research. S GROUP: (7) arrived in afib; (1) clot on TEE; (1) elevated anxiety in patient; (1) procedure scheduled late in day; (1) cardiac cath work-up needed. PLACEBO GROUP: (2) arrived in afib | Posted | Count of Participants | Participants | Twenty minutes post-dosage to end of induction protocol (approximately 10 minutes) |
|
|
|
| 0 |
| 71 |
| 0 |
| 71 |
| 0 |
| 71 |
| EG001 | (S)-Propafenone | Single intravenous dose of (S)-propafenone (1mg/kg) infused over 10 minutes (S)-Propafenone | 0 | 75 | 0 | 75 | 0 | 75 |
| EG002 | Placebo | Placebo (normal saline) is infused over 10 minutes Placebo | 0 | 19 | 0 | 19 | 0 | 19 |
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| D013568 |
| Pathological Conditions, Signs and Symptoms |
| Title | Measurements |
|---|---|
|
| Stage 3 |
|
| Non-inducible AF/AFL |
|
| Title | Measurements |
|---|---|
|