Atrial FibrillationPhase 1/2NCT02498769
Temporary Autonomic Blockade to Prevent Atrial Fibrillation After Cardiac Surgery
A Phase 1/2 study testing Botulinum Toxin Type A in people with Atrial Fibrillation, run by Joseph Mathew, M.D. at 1 site in United States.
Trial summary
In this study, the investigators aim to determine whether injecting botulinum toxin into epicardial fat pads is efficacious and safe for decreasing postoperative atrial fibrillation (POAF) after cardiac surgery. Read more about this study
- Who is it for?
- Ages 50 to 90 years
- Conditions the study is for
- Atrial Fibrillation
- What is being tested?
- Botulinum Toxin Type A
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 130 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2015to 1 Dec 2018
- 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 50 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Undergoing cardiac surgery with cardiopulmonary bypass via median sternotomy
- coronary artery bypass graft (CABG)
- valve surgery
- CABG + valve surgery
Who cannot join
- < 50years of age
- > 90years of age
- chronic AF or AF at the time of screening
- preoperative heart block (second degree or greater)
- LVEF < 25%
- renal failure
Show all 15Show fewer
- hepatic failure
- known sensitivity to Botulinum toxin
- debilitating neuromuscular disease
- preoperative need for inotropes/vasopressors or intra-aortic balloon pump
- planned MAZE procedure
- history of catheter ablation for AF
- use of Vaughan-Williams class I or III drugs within 5 elimination half lives (or within 2 months for amiodarone)
- undergoing minimally-invasive cardiac surgery
- prior cardiac surgery
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
In this study, the investigators aim to determine whether injecting botulinum toxin into epicardial fat pads is efficacious and safe for decreasing postoperative atrial fibrillation (POAF) after cardiac surgery. The investigators will test the hypothesis that botulinum toxin injected into the epicardial fat pads reduces POAF and length of stay (LOS) without increasing adverse events. This will be a prospective randomized trial of 130 patients undergoing coronary artery bypass graft (CABG), valve surgery or CABG + valve surgery with cardiopulmonary bypass. Patients will be randomized to receive either botulinum toxin (50 units per fat pad, n=65) or normal saline/placebo (1 mL per fat pad, n=65) injected into epicardial fat pads. All patients will receive standardized anesthetic, surgical, and post-surgical care. The primary outcome in this study will be time to occurrence of in-hospital POAF. Based on previous work and a pilot trial showing a pronounced reduction (relative risk reduction 77%) in POAF after injecting botulinum into the epicardial fat pads, the investigators anticipate a significant reduction in the risk for POAF with epicardial botulinum in this cohort, which includes valve surgery patients.
Read the detailed description
Purpose of the study: A pilot study to determine whether injecting botulinum toxin into epicardial fat pads is efficacious and safe for decreasing postoperative atrial fibrillation (POAF) after cardiac surgery
Hypothesis to be tested: Botulinum toxin injected into the epicardial fat pads reduces POAF.
Design and Procedures: This will be a prospective randomized pilot trial of 130 patients undergoing coronary artery bypass graft (CABG), valve surgery or CABG + valve surgery via median sternotomy with cardiopulmonary bypass. Patients <50 years of age, with chronic atrial fibrillation, prior cardiac surgery, EF<25%, preoperative inotropic support, hepatic or renal failure, known sensitivity to botulinum toxin, debilitating neuromuscular disease, or those with a history of atrioventricular block will be excluded from the study. Prior to surgery, all patients will have baseline Mini-Mental State Examination (MMSE) and blood sampling from an indwelling arterial line or venipuncture for measurement of inflammatory and genomic markers. Half of the patients will be randomized to receive injection of epicardial botulinum toxin in addition to standard of care, as described below. The other half will receive epicardial injection of normal saline.
Institution of cardiopulmonary bypass will be performed according to the routine surgical protocol. After instituting CPB, botulinum toxin (or normal saline) injections will be performed by the surgeon. This dose was selected given the prior report of its effectiveness in preventing POAF after cardiac surgery in a small pilot study.(Pokushalov et al., 2014) After completion of surgery and separation from CPB, patients will proceed along the institutional Cardiac Surgical Caremap. All patients will be monitored with continuous ECG (telemetry) until hospital discharge. POAF will be diagnosed by telemetry or 12-lead ECG, and will be defined as new-onset if it occurs postoperatively at any time before hospital discharge. POAF, if it occurs, will be treated as per routine of care. POAF will be defined as any detectable atrial fibrillation before discharge that lasts >30 seconds. On postoperative day (POD) 4, a member of the study team will visit each patient to administer the MMSE and capture a 5-minute ECG with a Holter monitor. In addition, patients will be contacted monthly for 4 months and at one year after surgery for follow up, and medical records will be reviewed for evidence of readmissions, arrhythmias, or other adverse events.
- Conditions
- Atrial Fibrillation
- Being tested
- Botulinum Toxin Type A, Placebo
- Keywords
- Cardiac Surgery, Postoperative Complications, Autonomic Nerve Block
- Medical subject headings
- Atrial Fibrillation, Postoperative Complications
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called Botox, Onabotulinumtoxin A
The botulinum toxin will be injected into epicardial fat pads shortly after cardiopulmonary bypass is initiated.
PlaceboDrug
Also called normal saline
| Study group | Role | What they receive |
|---|---|---|
| Epicardial Botulinum | Experimental | After instituting cardiopulmonary bypass (CPB), botulinum toxin injections will be performed by the surgeon as follows: Using a standard sterile insulin syringe with a 27g needle, surgeons will inject each of the epicardial fat pads with 50U (1mL) of botulinum toxin (OnabotulinumtoxinA, Botox®). After completion of surgery and separation from CPB, patients will proceed along the institutional Cardiac Surgical Caremap. All patients will be monitored with continuous ECG (telemetry) until hospital discharge. POAF will be diagnosed by telemetry or 12-lead ECG, and will be defined as new-onset if it occurs postoperatively at any time before hospital discharge. Receives: Drug: Botulinum Toxin Type A |
| Epicardial Placebo | Placebo comparator | After instituting cardiopulmonary bypass (CPB), placebo (normal saline) injections will be performed by the surgeon as follows: Using a standard sterile insulin syringe with a 27g needle, surgeons will inject each of the epicardial fat pads with 1mL of normal saline. After completion of surgery and separation from CPB, patients will proceed along the institutional Cardiac Surgical Caremap. All patients will be monitored with continuous ECG (telemetry) until hospital discharge. POAF will be diagnosed by telemetry or 12-lead ECG, and will be defined as new-onset if it occurs postoperatively at any time before hospital discharge. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to In-hospital Post-operative Atrial Fibrillation (POAF)
Patients will be seen on a daily basis and the timing of POAF compared between groups. The occurrence of in-hospital POAF will be tracked throughout the hospitalization (up to two weeks) and the time from surgery to the first and subsequent episodes of POAF recorded and compared between groups. POAF will be determined by ECG or telemetry.
Measured: From the time of ICU arrival until the time of first documented POAF, or discharge whichever came first, assessed up to 2 weeks
Secondary outcomes (3)
Number of Participants With In-hospital POAF
Patients will be seen on a daily basis and the occurrence of POAF compared between groups.
Measured: The incidence of in-hospital POAF will be tracked throughout the hospitalization (up to two weeks)
Length of Stay
Total and ICU length of stay will be determined by examining medical records for the length of inpatient hospitalization, assessed over the entire study period (up to two years). ICU and hospital LOS will be recorded and compared between groups
Measured: ICU length of stay was measured from time of surgery to time of ICU discharge. Post-operative length of stay was measured from time of surgery to time of hospital discharge.
Number of Participants With Adverse Events
The total number of postoperative complications (including infectious, neurologic, and renal complications, as well as mortality) and the number of subjects with complications will be monitored and compared between groups.
Measured: Adverse events from the time of surgery through hospital discharge, up to 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2015 (estimated)
- Study startSep 2015
- Primary completion28 Sep 2017
- Study completion1 Dec 2018
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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- Joseph Mathew, M.D.
- Sponsor type
- University, hospital or other
- Collaborators
- Foundation for Anesthesia Education and Research, American Heart Association
- Responsible party
- Sponsor-investigator, Joseph Mathew, M.D., Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02498769
- Sponsor's protocol ID
- Pro00061607
- Status last verified
- Feb 2019
- First submitted
- 8 Jul 2015
- Last updated
- 22 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Oh S, Choi EK, Zhang Y, Mazgalev TN. Botulinum toxin injection in epicardial autonomic ganglia temporarily suppresses vagally mediated atrial fibrillation. Circ Arrhythm Electrophysiol. 2011 Aug;4(4):560-5. doi: 10.1161/CIRCEP.111.961854. Epub 2011 Jun 9.
PubMed 21659633Pokushalov E, Kozlov B, Romanov A, Strelnikov A, Bayramova S, Sergeevichev D, Bogachev-Prokophiev A, Zheleznev S, Shipulin V, Salakhutdinov N, Lomivorotov VV, Karaskov A, Po SS, Steinberg JS. Botulinum toxin injection in epicardial fat pads can prevent recurrences of atrial fibrillation after cardiac surgery: results of a randomized pilot study. J Am Coll Cardiol. 2014 Aug 12;64(6):628-9. doi: 10.1016/j.jacc.2014.04.062. No abstract available.
PubMed 25104535
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Temporary Autonomic Blockade to Prevent Atrial Fibrillation After Cardiac Surgery
- ClinicalTrials.gov ID
- NCT02498769
- Acronym / sponsor ID
- Pro00061607
- Conditions
- Atrial Fibrillation
- Keywords
- Cardiac Surgery, Postoperative Complications, Autonomic Nerve Block
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- Joseph Mathew, M.D.University, hospital or other
- Collaborators
- Foundation for Anesthesia Education and Research, American Heart Association
- Study start
- Sep 2015 (actual)
- Primary completion
- 28 Sep 2017 (actual)
- Study completion
- 1 Dec 2018 (actual)
- First posted
- 15 Jul 2015 (estimated)
- Results
- Posted 7 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this study, the investigators aim to determine whether injecting botulinum toxin into epicardial fat pads is efficacious and safe for decreasing postoperative atrial fibrillation (POAF) after cardiac surgery. The investigators will test the hypothesis that botulinum toxin injected into the epicardial fat pads reduces POAF and length of stay (LOS) without increasing adverse events. This will be a prospective randomized trial of 130 patients undergoing coronary artery bypass graft (CABG), valve surgery or CABG + valve surgery with cardiopulmonary bypass. Patients will be randomized to receive either botulinum toxin (50 units per fat pad, n=65) or normal saline/placebo (1 mL per fat pad, n=65) injected into epicardial fat pads. All patients will receive standardized anesthetic, surgical, and post-surgical care. The primary outcome in this study will be time to occurrence of in-hospital POAF. Based on previous work and a pilot trial showing a pronounced reduction (relative risk reduction 77%) in POAF after injecting botulinum into the epicardial fat pads, the investigators anticipate a significant reduction in the risk for POAF with epicardial botulinum in this cohort, which includes valve surgery patients.
Detailed description
Purpose of the study: A pilot study to determine whether injecting botulinum toxin into epicardial fat pads is efficacious and safe for decreasing postoperative atrial fibrillation (POAF) after cardiac surgery
Hypothesis to be tested: Botulinum toxin injected into the epicardial fat pads reduces POAF.
Design and Procedures: This will be a prospective randomized pilot trial of 130 patients undergoing coronary artery bypass graft (CABG), valve surgery or CABG + valve surgery via median sternotomy with cardiopulmonary bypass. Patients <50 years of age, with chronic atrial fibrillation, prior cardiac surgery, EF<25%, preoperative inotropic support, hepatic or renal failure, known sensitivity to botulinum toxin, debilitating neuromuscular disease, or those with a history of atrioventricular block will be excluded from the study. Prior to surgery, all patients will have baseline Mini-Mental State Examination (MMSE) and blood sampling from an indwelling arterial line or venipuncture for measurement of inflammatory and genomic markers. Half of the patients will be randomized to receive injection of epicardial botulinum toxin in addition to standard of care, as described below. The other half will receive epicardial injection of normal saline.
Institution of cardiopulmonary bypass will be performed according to the routine surgical protocol. After instituting CPB, botulinum toxin (or normal saline) injections will be performed by the surgeon. This dose was selected given the prior report of its effectiveness in preventing POAF after cardiac surgery in a small pilot study.(Pokushalov et al., 2014) After completion of surgery and separation from CPB, patients will proceed along the institutional Cardiac Surgical Caremap. All patients will be monitored with continuous ECG (telemetry) until hospital discharge. POAF will be diagnosed by telemetry or 12-lead ECG, and will be defined as new-onset if it occurs postoperatively at any time before hospital discharge. POAF, if it occurs, will be treated as per routine of care. POAF will be defined as any detectable atrial fibrillation before discharge that lasts >30 seconds. On postoperative day (POD) 4, a member of the study team will visit each patient to administer the MMSE and capture a 5-minute ECG with a Holter monitor. In addition, patients will be contacted monthly for 4 months and at one year after surgery for follow up, and medical records will be reviewed for evidence of readmissions, arrhythmias, or other adverse events.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Epicardial Botulinum | Experimental | Drug: Botulinum Toxin Type AAfter instituting cardiopulmonary bypass (CPB), botulinum toxin injections will be performed by the surgeon as follows: Using a standard sterile insulin syringe with a 27g needle, surgeons will inject each of the epicardial fat pads with 50U (1mL) of botulinum toxin (OnabotulinumtoxinA, Botox®). After completion of surgery and separation from CPB, patients will proceed along the institutional Cardiac Surgical Caremap. All patients will be monitored with continuous ECG (telemetry) until hospital discharge. POAF will be diagnosed by telemetry or 12-lead ECG, and will be defined as new-onset if it occurs postoperatively at any time before hospital discharge. |
| Epicardial Placebo | Placebo comparator | Drug: PlaceboAfter instituting cardiopulmonary bypass (CPB), placebo (normal saline) injections will be performed by the surgeon as follows: Using a standard sterile insulin syringe with a 27g needle, surgeons will inject each of the epicardial fat pads with 1mL of normal saline. After completion of surgery and separation from CPB, patients will proceed along the institutional Cardiac Surgical Caremap. All patients will be monitored with continuous ECG (telemetry) until hospital discharge. POAF will be diagnosed by telemetry or 12-lead ECG, and will be defined as new-onset if it occurs postoperatively at any time before hospital discharge. |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Undergoing cardiac surgery with cardiopulmonary bypass via median sternotomy
- coronary artery bypass graft (CABG)
- valve surgery
- CABG + valve surgery
Key exclusion criteria (15 listed)
- < 50years of age
- > 90years of age
- chronic AF or AF at the time of screening
- preoperative heart block (second degree or greater)
- LVEF < 25%
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 |
|---|---|---|
| Botulinum Toxin Type AAlso: Botox, Onabotulinumtoxin AThe botulinum toxin will be injected into epicardial fat pads shortly after cardiopulmonary bypass is initiated. | Drug | Epicardial Botulinum |
| PlaceboAlso: normal saline | Drug | Epicardial Placebo |
Primary outcome
Time to In-hospital Post-operative Atrial Fibrillation (POAF)
Time frame: From the time of ICU arrival until the time of first documented POAF, or discharge whichever came first, assessed up to 2 weeks
Patients will be seen on a daily basis and the timing of POAF compared between groups. The occurrence of in-hospital POAF will be tracked throughout the hospitalization (up to two weeks) and the time from surgery to the first and subsequent episodes of POAF recorded and compared between groups. POAF will be determined by ECG or telemetry.
3 secondary outcomes
Number of Participants With In-hospital POAF
Time frame: The incidence of in-hospital POAF will be tracked throughout the hospitalization (up to two weeks)
Length of Stay
Time frame: ICU length of stay was measured from time of surgery to time of ICU discharge. Post-operative length of stay was measured from time of surgery to time of hospital discharge.
Number of Participants With Adverse Events
Time frame: Adverse events from the time of surgery through hospital discharge, up to 2 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21659633Oh S, Choi EK, Zhang Y, Mazgalev TN. Botulinum toxin injection in epicardial autonomic ganglia temporarily suppresses vagally mediated atrial fibrillation. Circ Arrhythm Electrophysiol. 2011 Aug;4(4):560-5. doi: 10.1161/CIRCEP.111.961854. Epub 2011 Jun 9.
- Background: PubMed 25104535Pokushalov E, Kozlov B, Romanov A, Strelnikov A, Bayramova S, Sergeevichev D, Bogachev-Prokophiev A, Zheleznev S, Shipulin V, Salakhutdinov N, Lomivorotov VV, Karaskov A, Po SS, Steinberg JS. Botulinum toxin injection in epicardial fat pads can prevent recurrences of atrial fibrillation after cardiac surgery: results of a randomized pilot study. J Am Coll Cardiol. 2014 Aug 12;64(6):628-9. doi: 10.1016/j.jacc.2014.04.062. No abstract available.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Botulinum Toxin Type A in people with Atrial Fibrillation, run by Joseph Mathew, M.D. 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 15 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 22 Feb 2019. 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 7 Dec 2018). 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?
Time to In-hospital Post-operative Atrial Fibrillation (POAF) (time frame: From the time of ICU arrival until the time of first documented POAF, or discharge whichever came first, assessed up to 2 weeks). 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 NCT02498769, 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 22 Feb 2019.