Atrial FibrillationPRECAFNCT03646643
Prospective Elimination Of Distal Coronary Sinus-Left Atrial Connections for Atrial Fibrillation Ablation Trial
A study testing Standard Atrial fibrillation ablation and Coronary sinus to left atrium connection elimination in people with Atrial Fibrillation and Arrhythmias, Cardiac, run by University of Pennsylvania at 1 site in United States.
Trial summary
Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting millions of people in the US and around the world. Over the last 20 years, catheter based AF ablation has been widely adopted offering improved symptom control for many patients worldwide. However, long-term success rates remain suboptimal. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation, Arrhythmias, Cardiac
- What is being tested?
- Standard Atrial fibrillation ablation and Coronary sinus to left atrium connection elimination
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Aug 2018to 22 Sep 2021
- Phase
- Interventional
- 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
- Patients with paroxysmal or persistent atrial fibrillation; AND Undergoing first AF ablation; AND Age ≥ 18 years.
Who cannot join
- Previous left atrial ablation; Women currently pregnant; Mental or physical inability to take part in the study; Known terminally ill patients.
Trial locations and contacts
1 site in 1 country.
United States1 site
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting millions of people in the US and around the world. Over the last 20 years, catheter based AF ablation has been widely adopted offering improved symptom control for many patients worldwide. However, long-term success rates remain suboptimal. Prior work indicates that distal connections between coronary sinus musculature and the left atrium exist and provide a substrate for single or multiple reentry beats as a trigger for atrial fibrillation. In this trial, the investigators will examine the efficacy of elimination of distal connection(s) between coronary sinus and left atrial musculature for suppression of recurrent atrial arrhythmias.
Read the detailed description
Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting millions of people in the US and around the world. Over the last 20 years, catheter based AF ablation has been widely adopted. However, long-term success rates fhave been reported to be as low as 50% and 20% for paroxysmal and persistent AF, respectively. To achieve permanent arrhythmia suppression, repeated ablation procedures are often needed. Prior work indicates that distal connections between coronary sinus musculature and the left atrium provide a substrate for single or multiple reentry beats as a trigger for atrial fibrillation. In this prospective randomized trial the investigators will define the efficacy of elimination of distal connections between coronary sinus and left atrial musculature for suppression of recurrent atrial arrhythmias. Patients will be randomly assigned to standard of care ablation (pulmonary vein isolation and non pulmonary vein trigger ablations) alone, or standard of care ablation augmented by distal coronary sinus to left atrial connection elimination.
- Conditions
- Atrial Fibrillation, Arrhythmias, Cardiac
- Being tested
- Standard Atrial fibrillation ablation, Coronary sinus to left atrium connection elimination
- Keywords
- Atrial fibrillation, Coronary sinus-left atrium connection, Ablation
- Medical subject headings
- Atrial Fibrillation, Arrhythmias, Cardiac
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard Atrial fibrillation ablationProcedure or surgery
Also called Pulmonary vein isolation, Non-PV triggers ablation
The AF ablation procedures should follow the sequence below: Diagnostic catheter placement Electrophysiology study; Transseptal puncture; Left atrial electro-anatomical mapping is required prior to an ablation procedure. Post ablation pacing procedure(s) and/or infusion of cardiac medications to localize triggers/ assess and localize pulmonary vein reconnections (e.g., Adenosine, Isoproterenol 2-20 mcg/min). Study procedure requirements are outlined below: Isolation of all pulmonary veins and Non-pulmonary vein trigger ablation for all patients. Linear ablation lines are only required to treat documented macro-reentry atrial tachycardias and limited to the following targets only: LA roof line, mitral valve isthmus line, LA floor line, right atrial carvotricuspid isthmus linear ablation.
Coronary sinus to left atrium connection eliminationProcedure or surgery
Distal coronary sinus pacing will be utilized to localize distal connections between the main coronary sinus body and the left atrium. Focal lesions will be applied to early left atrial activation sites, until no distal coronary sinus to left atrial connections are electrically manifest. If vein of marshall connections to the left atrium are present, differential pacing will be utilized to prove the lack of distal coronary sinus to left atrium connections.
| Study group | Role | What they receive |
|---|---|---|
| PVI, non-PV triggers | Active comparator | Interventions: Atrial fibrillation ablation, including conventional pulmonary vein isolation (PVI) and non-PV triggers ablation. Receives: Procedure: Standard Atrial fibrillation ablation |
| PVI, non-PV triggers & CS-LA connection | Active comparator | Interventions: Atrial fibrillation ablation, including conventional pulmonary vein isolation (PVI) and non-PV triggers ablation in addition to coronary sinus-left atrium connection elimination. Distal coronary sinus pacing will be utilized to localize the earliest connection (aside from septal) from the coronary sinus to the left atrial musculature. Once localized, focal radiofrequency lesions will be applied at the discretion of the investigator until distal coronary sinus to left atrial connections are eliminated. Receives: Procedure: Standard Atrial fibrillation ablation; Procedure: Coronary sinus to left atrium connection elimination |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence Rate of Atrial Arrhythmias
The primary endpoint of the study is recurrence rate of atrial arrhythmia following ablation. The primary endpoint will be assessed using survival statistical models measuring time to failure among the two study arms. Failure is defined as a non-self-terminating bout of atrial fibrillation, atrial flutter, or atrial tachycardia >30 seconds in duration following the 90-day post-ablation blanking period. If no AF occurs during the study period, censoring will occur at 180±45 days post-ablation.
Measured: Time to atrial arrhythmia recurrence will be recorded as time to the first ECG or monitor that shows atrial arrhythmia recurrence between the end of the blanking period (90 days post ablation) and the end of the study (180±45 days post ablation).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2018
- Study start18 Aug 2018
- Primary completion20 Nov 2019
- Study completion22 Sep 2021
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 (5)Papers the sponsor has linked to this study.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The PRECAF study is designed as a randomized, single-blind, small scale pilot study. Enrolled subjects who satisfy all eligibility criteria will then undergo the ablation procedure. Study randomization will be performed in a 1:1 fashion using the Urn Randomization program (https://health.uconn.edu/community-medicine/programs/health-services-research-unit/project-match/urn-randomization/) while balancing sex and AF type (paroxysmal and non-paroxysmal). The master list of study assignments will be kept by the study coordinator in a password protected and encrypted computer. After the ablation procedure, participants will remain in the study for 6 months. A 30-day event monitor will be used for the first month after ablation. Then, regular clinic visits at 6 weeks and 6 months will be arranged after ablation with 12 lead electrocardiogram check-up. In the last month, a 30-day event monitor will again be utilized to detect atrial arrhythmia recurrence.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Saman Nazarian, University of Pennsylvania
- Investigators
- Saman Nazarian, M.D., Ph.D, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03646643
- Sponsor's protocol ID
- 829990
- Acronym
- PRECAF
- Status last verified
- Oct 2024
- First submitted
- 6 Aug 2018
- Last updated
- 29 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Information about study subjects will be kept confidential and managed according to the requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA). Those regulations require a signed subject authorization informing the subject of the following: * What protected health information (PHI) will be collected from subjects in this study * Who will have access to that information and why * Who will use or disclose that information * The rights of a research subject to revoke their authorization for use of their PHI. In the event that a subject revokes authorization to collect or use PHI, the investigator, by regulation, retains the ability to use all information collected prior to the revocation of subject authorization. For subjects that have revoked authorization to collect or use PHI, attempts should be made to obtain permission to collect at least vital status (i.e. that the subject is alive) at the end of their scheduled study period.
Publications
Kim MH, Lin J, Kreilick C, Foltz Boklage SH. Total costs and atrial fibrillation ablation success or failure in Medicare-aged patients in the United States. Adv Ther. 2010 Sep;27(9):600-12. doi: 10.1007/s12325-010-0060-3. Epub 2010 Aug 9.
PubMed 20700678Chauvin M, Shah DC, Haissaguerre M, Marcellin L, Brechenmacher C. The anatomic basis of connections between the coronary sinus musculature and the left atrium in humans. Circulation. 2000 Feb 15;101(6):647-52. doi: 10.1161/01.cir.101.6.647.
PubMed 10673257Huang D, Marine JE, Li JB, Zghaib T, Ipek EG, Sinha S, Spragg DD, Ashikaga H, Berger RD, Calkins H, Nazarian S. Association of Rate-Dependent Conduction Block Between Eccentric Coronary Sinus to Left Atrial Connections With Inducible Atrial Fibrillation and Flutter. Circ Arrhythm Electrophysiol. 2017 Jan;10(1):e004637. doi: 10.1161/CIRCEP.116.004637.
PubMed 28039281Antz M, Otomo K, Arruda M, Scherlag BJ, Pitha J, Tondo C, Lazzara R, Jackman WM. Electrical conduction between the right atrium and the left atrium via the musculature of the coronary sinus. Circulation. 1998 Oct 27;98(17):1790-5. doi: 10.1161/01.cir.98.17.1790.
PubMed 9788835Kuo L, Frankel DS, Lin A, Arkles J, Hyman M, Santangeli P, Marchlinski FE, Nazarian S. PRECAF Randomized Controlled Trial. Circ Arrhythm Electrophysiol. 2021 Jan;14(1):e008993. doi: 10.1161/CIRCEP.120.008993. Epub 2020 Dec 10.
PubMed 33301361
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Elimination Of Distal Coronary Sinus-Left Atrial Connections for Atrial Fibrillation Ablation Trial
- ClinicalTrials.gov ID
- NCT03646643
- Acronym / sponsor ID
- PRECAF / 829990
- Conditions
- Atrial Fibrillation, Arrhythmias, Cardiac
- Keywords
- Atrial fibrillation, Coronary sinus-left atrium connection, Ablation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 18 Aug 2018 (actual)
- Primary completion
- 20 Nov 2019 (actual)
- Study completion
- 22 Sep 2021 (actual)
- First posted
- 24 Aug 2018 (actual)
- Results
- Posted 29 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting millions of people in the US and around the world. Over the last 20 years, catheter based AF ablation has been widely adopted offering improved symptom control for many patients worldwide. However, long-term success rates remain suboptimal. Prior work indicates that distal connections between coronary sinus musculature and the left atrium exist and provide a substrate for single or multiple reentry beats as a trigger for atrial fibrillation. In this trial, the investigators will examine the efficacy of elimination of distal connection(s) between coronary sinus and left atrial musculature for suppression of recurrent atrial arrhythmias.
Detailed description
Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting millions of people in the US and around the world. Over the last 20 years, catheter based AF ablation has been widely adopted. However, long-term success rates fhave been reported to be as low as 50% and 20% for paroxysmal and persistent AF, respectively. To achieve permanent arrhythmia suppression, repeated ablation procedures are often needed. Prior work indicates that distal connections between coronary sinus musculature and the left atrium provide a substrate for single or multiple reentry beats as a trigger for atrial fibrillation. In this prospective randomized trial the investigators will define the efficacy of elimination of distal connections between coronary sinus and left atrial musculature for suppression of recurrent atrial arrhythmias. Patients will be randomly assigned to standard of care ablation (pulmonary vein isolation and non pulmonary vein trigger ablations) alone, or standard of care ablation augmented by distal coronary sinus to left atrial connection elimination.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- The PRECAF study is designed as a randomized, single-blind, small scale pilot study. Enrolled subjects who satisfy all eligibility criteria will then undergo the ablation procedure. Study randomization will be performed in a 1:1 fashion using the Urn Randomization program (https://health.uconn.edu/community-medicine/programs/health-services-research-unit/project-match/urn-randomization/) while balancing sex and AF type (paroxysmal and non-paroxysmal). The master list of study assignments will be kept by the study coordinator in a password protected and encrypted computer. After the ablation procedure, participants will remain in the study for 6 months. A 30-day event monitor will be used for the first month after ablation. Then, regular clinic visits at 6 weeks and 6 months will be arranged after ablation with 12 lead electrocardiogram check-up. In the last month, a 30-day event monitor will again be utilized to detect atrial arrhythmia recurrence.
| Arm | Type | Receives |
|---|---|---|
| PVI, non-PV triggers | Active comparator | Procedure: Standard Atrial fibrillation ablationInterventions: Atrial fibrillation ablation, including conventional pulmonary vein isolation (PVI) and non-PV triggers ablation. |
| PVI, non-PV triggers & CS-LA connection | Active comparator | Procedure: Standard Atrial fibrillation ablation, Procedure: Coronary sinus to left atrium connection eliminationInterventions: Atrial fibrillation ablation, including conventional pulmonary vein isolation (PVI) and non-PV triggers ablation in addition to coronary sinus-left atrium connection elimination. Distal coronary sinus pacing will be utilized to localize the earliest connection (aside from septal) from the coronary sinus to the left atrial musculature. Once localized, focal radiofrequency lesions will be applied at the discretion of the investigator until distal coronary sinus to left atrial connections are eliminated. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients with paroxysmal or persistent atrial fibrillation; AND Undergoing first AF ablation; AND Age ≥ 18 years.
Key exclusion criteria (1 listed)
- Previous left atrial ablation; Women currently pregnant; Mental or physical inability to take part in the study; Known terminally ill patients.
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 |
|---|---|---|
| Standard Atrial fibrillation ablationAlso: Pulmonary vein isolation, Non-PV triggers ablationThe AF ablation procedures should follow the sequence below: Diagnostic catheter placement Electrophysiology study; Transseptal puncture; Left atrial electro-anatomical mapping is required prior to an ablation procedure. Post ablation pacing procedure(s) and/or infusion of cardiac medications to localize triggers/ assess and localize pulmonary vein reconnections (e.g., Adenosine, Isoproterenol 2-20 mcg/min). Study procedure requirements are outlined below: Isolation of all pulmonary veins and Non-pulmonary vein trigger ablation for all patients. Linear ablation lines are only required to treat documented macro-reentry atrial tachycardias and limited to the following targets only: LA roof line, mitral valve isthmus line, LA floor line, right atrial carvotricuspid isthmus linear ablation. | Procedure or surgery | PVI, non-PV triggers, PVI, non-PV triggers & CS-LA connection |
| Coronary sinus to left atrium connection eliminationDistal coronary sinus pacing will be utilized to localize distal connections between the main coronary sinus body and the left atrium. Focal lesions will be applied to early left atrial activation sites, until no distal coronary sinus to left atrial connections are electrically manifest. If vein of marshall connections to the left atrium are present, differential pacing will be utilized to prove the lack of distal coronary sinus to left atrium connections. | Procedure or surgery | PVI, non-PV triggers & CS-LA connection |
Primary outcome
Recurrence Rate of Atrial Arrhythmias
Time frame: Time to atrial arrhythmia recurrence will be recorded as time to the first ECG or monitor that shows atrial arrhythmia recurrence between the end of the blanking period (90 days post ablation) and the end of the study (180±45 days post ablation).
The primary endpoint of the study is recurrence rate of atrial arrhythmia following ablation. The primary endpoint will be assessed using survival statistical models measuring time to failure among the two study arms. Failure is defined as a non-self-terminating bout of atrial fibrillation, atrial flutter, or atrial tachycardia >30 seconds in duration following the 90-day post-ablation blanking period. If no AF occurs during the study period, censoring will occur at 180±45 days post-ablation.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20700678Kim MH, Lin J, Kreilick C, Foltz Boklage SH. Total costs and atrial fibrillation ablation success or failure in Medicare-aged patients in the United States. Adv Ther. 2010 Sep;27(9):600-12. doi: 10.1007/s12325-010-0060-3. Epub 2010 Aug 9.
- Results publication: PubMed 10673257Chauvin M, Shah DC, Haissaguerre M, Marcellin L, Brechenmacher C. The anatomic basis of connections between the coronary sinus musculature and the left atrium in humans. Circulation. 2000 Feb 15;101(6):647-52. doi: 10.1161/01.cir.101.6.647.
- Results publication: PubMed 28039281Huang D, Marine JE, Li JB, Zghaib T, Ipek EG, Sinha S, Spragg DD, Ashikaga H, Berger RD, Calkins H, Nazarian S. Association of Rate-Dependent Conduction Block Between Eccentric Coronary Sinus to Left Atrial Connections With Inducible Atrial Fibrillation and Flutter. Circ Arrhythm Electrophysiol. 2017 Jan;10(1):e004637. doi: 10.1161/CIRCEP.116.004637.
- Results publication: PubMed 9788835Antz M, Otomo K, Arruda M, Scherlag BJ, Pitha J, Tondo C, Lazzara R, Jackman WM. Electrical conduction between the right atrium and the left atrium via the musculature of the coronary sinus. Circulation. 1998 Oct 27;98(17):1790-5. doi: 10.1161/01.cir.98.17.1790.
- Derived from this study: PubMed 33301361Kuo L, Frankel DS, Lin A, Arkles J, Hyman M, Santangeli P, Marchlinski FE, Nazarian S. PRECAF Randomized Controlled Trial. Circ Arrhythm Electrophysiol. 2021 Jan;14(1):e008993. doi: 10.1161/CIRCEP.120.008993. Epub 2020 Dec 10.
- Individual participant dataSharing planned: Yes. Information about study subjects will be kept confidential and managed according to the requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA). Those regulations require a signed subject authorization informing the subject of the following: * What protected health information (PHI) will be collected from subjects in this study * Who will have access to that information and why * Who will use or disclose that information * The rights of a research subject to revoke their authorization for use of their PHI. In the event that a subject revokes authorization to collect or use PHI, the investigator, by regulation, retains the ability to use all information collected prior to the revocation of subject authorization. For subjects that have revoked authorization to collect or use PHI, attempts should be made to obtain permission to collect at least vital status (i.e. that the subject is alive) at the end of their scheduled study period.
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Atrial Fibrillation (AF)
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.
Saman Nazarian, M.D., Ph.D principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Standard Atrial fibrillation ablation and Coronary sinus to left atrium connection elimination in people with Atrial Fibrillation and Arrhythmias, Cardiac, run by University of Pennsylvania 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 1 inclusion and 1 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: finished, as of the sponsor's last update on 29 Nov 2024. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Nov 2024). 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?
Recurrence Rate of Atrial Arrhythmias (time frame: Time to atrial arrhythmia recurrence will be recorded as time to the first ECG or monitor that shows atrial arrhythmia recurrence between the end of the blanking period (90 days post ablation) and the end of the study (180±45 days post ablation).). 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 NCT03646643, which also lists 5 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 29 Nov 2024.