Atrial FibrillationPhase 1/2NCT02710669
New Formulations of Propafenone to Treat Atrial Fibrillation
A Phase 1/2 study testing (R)-propafenone and (S)-Propafenone in people with Atrial Fibrillation, run by Vanderbilt University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation
- What is being tested?
- (R)-propafenone and (S)-Propafenone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 193 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2016to Apr 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- History of atrial fibrillation
- Greater than or equal to 18 years of age
- Scheduled to undergo an atrial fibrillation ablation procedure
- Able to provide written informed consent
Who cannot join
- 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
- sick sinus syndrome indicated by the inability to previously tolerate an antiarrhythmic drug due to bradycardia
- sinus bradycardia with a heart rate less than 50 beats per minute at the time of study drug administration
- right bundle branch block, left bundle branch block, or bifascicular block
Show all 23Show fewer
- PR-interval > 280ms, or history of 2nd or 3rd degree atrioventricular block
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Comparison of (R) and (S) Propafenone for Prevention of Atrial Fibrillation Induction
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.
Read the detailed description
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.
- Conditions
- Atrial Fibrillation
- Being tested
- (R)-propafenone, (S)-Propafenone, Placebo
- Keywords
- ablation
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
(R)-propafenoneDrug
(S)-PropafenoneDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| (R)-propafenone | Experimental | Single intravenous dose of (R)-propafenone (2mg/kg) infused over 10 minutes Receives: Drug: (R)-propafenone |
| (S)-Propafenone | Active comparator | Single intravenous dose of (S)-propafenone (2mg/kg) infused over 10 minutes Receives: Drug: (S)-Propafenone |
| Placebo | Placebo comparator | Placebo (normal saline) is infused over 10 minutes Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Twenty minutes post-dosage to end of induction protocol (approximately 10 minutes)
Secondary outcomes (2)
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 1 measured the AV block (Wenckebach) cycle length (AVBCL), AV node effective refractory period (AVN ERP) and atrial ERP (AERP). AVN ERP and AERP were measured at drive trains (S1) of 600 ms and 450 ms. Extrastimuli (S2) were introduced starting at a coupling interval of 500ms and decremented by 10ms with each pacing train.
- Stage 2 consisted of 15-beat bursts from the CS proximal electrode. The starting cycle length was 250ms, which was decremented by 10ms with each burst. A 10-second rest period was used between bursts. Step 2 was complete when 1:1 atrial capture was lost or a minimum cycle length of 180ms was reached.
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.
Measured: 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.
Measured: Twenty minutes post-dosage to end of induction protocol (approximately 10 minutes)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2016 (estimated)
- Study startOct 2016
- Primary completion11 Mar 2020
- Study completionApr 2020
Why it stopped: Study halted/terminated prematurely due to COVID.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 193 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Bjorn Knollmann, Vanderbilt University
- Investigators
- Bjorn Knollmann, MD/PhD, Principal investigator, Vanderbilt UniversityBen Shoemaker, MD, Study director, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02710669
- Sponsor's protocol ID
- 151952
- Other IDs
- 1R01HL124935-01A1
- Status last verified
- Jun 2022
- First submitted
- 12 Mar 2016
- Last updated
- 3 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
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.
PubMed 24493699Shoemaker 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.
PubMed 36166682
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of (R) and (S) Propafenone for Prevention of Atrial Fibrillation Induction
- ClinicalTrials.gov ID
- NCT02710669
- Acronym / sponsor ID
- 151952
- Conditions
- Atrial Fibrillation
- Keywords
- ablation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study halted/terminated prematurely due to COVID.
- Enrolment
- 193 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Oct 2016
- Primary completion
- 11 Mar 2020 (actual)
- Study completion
- Apr 2020 (actual)
- First posted
- 17 Mar 2016 (estimated)
- Results
- Posted 14 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| (R)-propafenone | Experimental | Drug: (R)-propafenoneSingle intravenous dose of (R)-propafenone (2mg/kg) infused over 10 minutes |
| (S)-Propafenone | Active comparator | Drug: (S)-PropafenoneSingle intravenous dose of (S)-propafenone (2mg/kg) infused over 10 minutes |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo (normal saline) is infused over 10 minutes |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- History of atrial fibrillation
- Greater than or equal to 18 years of age
- Scheduled to undergo an atrial fibrillation ablation procedure
- Able to provide written informed consent
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| (R)-propafenone | Drug | (R)-propafenone |
| (S)-Propafenone | Drug | (S)-Propafenone |
| Placebo | Drug | Placebo |
Primary outcome
Number of Participants With Successful Induction of 30 Seconds of Atrial Fibrillation/Atrial Flutter
Time frame: Twenty minutes post-dosage to end of induction protocol (approximately 10 minutes)
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.
2 secondary outcomes
Number of Participants With Successful Inducibility of Atrial Fibrillation/Atrial Flutter Expressed as an Ordinal Variable Based on Stage of the Induction Protocol
Time frame: Twenty minutes post-dosage to end of induction protocol (approximately 10 minutes)
Number of Participants With Successful Induction of 30 Seconds of Atrial Flutter
Time frame: Twenty minutes post-dosage to end of induction protocol (approximately 10 minutes)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24493699Faggioni 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.
- Derived from this study: PubMed 36166682Shoemaker 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bjorn Knollmann, MD/PhD principal investigator
Vanderbilt University
Ben Shoemaker, MD study director
Vanderbilt University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing (R)-propafenone and (S)-Propafenone in people with Atrial Fibrillation, run by Vanderbilt University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Successful Induction of 30 Seconds of Atrial Fibrillation/Atrial Flutter (time frame: Twenty minutes post-dosage to end of induction protocol (approximately 10 minutes)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02710669, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2022.