Atrial FibrillationNCT05464940
Impact of Intravenous Caffeine on Atrial Electrical Properties and Potential Arrythmia Induction
A study testing Intravenous caffeine in people with Atrial Fibrillation, run by Kansas City Heart Rhythm Research Foundation at 9 sites in United States.
Trial summary
This "How caffeine Induces Atrial Tachyarrhythmias" trial will be a multi-center, randomized, double-blinded trial of intravenous caffeine versus placebo among patients undergoing pulmonary vein isolation procedures for Atrial Fibrillation(AF). Read more about this study
- Who is it for?
- Ages 21 to 90 years
- Conditions the study is for
- Atrial Fibrillation
- What is being tested?
- Intravenous caffeine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 9 sitesUnited States
- Study dates
- Sep 2025to Jun 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 21 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All adult patients from 21-90 years of age with new onset Paroxysmal Atrial Fibrillation presenting in sinus rhythm or AF of recent onset (the latter confirmed by sinus rhythm documented no more than 1 week prior) undergoing AF ablation will be included in the study.
Who cannot join
- Patients will be excluded if any of the following were identified:
- History of substance abuse or alcoholism.
- Left ventricular ejection fraction <50%.
- Liver dysfunction.
- Pregnancy.
- Inability to give informed consent.
Show all 9Show fewer
- Amiodarone uses within 1 month prior to procedure.
- AAD use within 24 h prior to the procedure
- Severe intolerance to caffeine.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Texas Cardiac Arrythmia Institute
Austin, Texas, 78705
Andrea Natale
Centerpoint Medical Center Clinic
Independence, Missouri, 64057
Donita Atkins
Centerpoint Medical Center
Independence, Missouri, 64057
Donita Atkins
Research Medical Center Clinic
Kansas City, Missouri, 64032
Donita Atkins
Research Medical Center
Kansas City, Missouri, 64032
Donita Atkins
Loma Linda University
Loma Linda, California, 92350
Jalaj Garg
Menorah Medical Center
Overland Park, Kansas, 66209
Donita Atkins
Kansas City Heart Rhythm Institute
Overland Park, Kansas, 66211
Donita Atkins
Overland Park Regional Medical Center
Overland Park, Kansas, 66215
Donita Atkins
About this study
Official title: Impact of Intravenous Caffeine on Atrial Electrical Properties and Potential Arrythmia Induction in Patients With Paroxysmal Atrial Fibrillation: The COFFEE-AF Trial
This "How caffeine Induces Atrial Tachyarrhythmias" trial will be a multi-center, randomized, double-blinded trial of intravenous caffeine versus placebo among patients undergoing pulmonary vein isolation procedures for Atrial Fibrillation(AF).
Read the detailed description
The mechanism by which caffeine might change cardiac electrophysiologic properties is largely unknown. Most of the prior studies conducted have evaluated the correlation based on the premise of oral consumption. One caveat among such study designs can be underreporting or overreporting the amount of caffeine ingested. To this date, no clinical trials exist that has studied the in vivo effects of caffeine to assess the atrial refractory period and conduction velocity and its potential to cause atrial or ventricular ectopy or sustained arrythmia induction including Atrial Tachycardia(AT)/Atrial Fibrillation(AF)/Ventricular Tachycardia(VT)/Ventricular Fibrillation(VF). As it is hypothesized that decreasing the atrial refractory period can render atria more prone to fibrillation. The pulmonary veins have proven integral to AF pathophysiology, the relationship between pulmonary vein electrophysiology and lifestyle factors in particular has not previously been assessed. It is also not clear if caffeine increases the risk of AF on those patients with known AF diagnosis. To bridge this gap, a randomized controlled trial is proposed to assess the effects of intravenous caffeine on atrial activity during AF ablation procedures.
- Conditions
- Atrial Fibrillation
- Being tested
- Intravenous caffeine, Masked Placebo
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous caffeineOther
Group assigned to receive caffeine will receive intravenous(IV) caffeine and sodium benzoate infusion starting at 250-500 mg.
This method will use an automated algorithm that adjusts the flow of the infusion depending on the individual's sex and weight and then in a serial fashion in response to blood caffeine measurements. Serial blood caffeine measurements at pre-determined intervals according to the algorithm will be until a steady state is obtained.
Masked PlaceboOther
The patients assigned to the masked placebo will receive 5% dextrose in 0.45% saline using the same infusion protocol for a random length of time that was within 1 standard deviation(SD) of the mean time to achieve a steady state using the caffeine protocol (17+4 min).
To maintain blinding, caffeine blood concentration measurements that will be randomly generated within 2 SDs of the predicted values calculated by the algorithm will be used and verbally communicated for placebo infusions.
| Study group | Role | What they receive |
|---|---|---|
| Group assigned to receive caffeine | Active comparator | Not described Receives: Other: Intravenous caffeine |
| Group assigned to receive masked placebo | Placebo comparator | Not described Receives: Other: Masked Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Atrial Fibrillation Induction
Induction of Atrial fibrillation will be attempted by pacing and isoproterenol infusion following study drug infusion. The ability to induce atrial fibrillation (yes or no) will be recorded as the primary outcome.
Measured: 1 day
Secondary outcomes (4)
Number of patients with Site-specific changes in AERP(Atrial Effective Refractory Period)
It helps assess changes in AERP in milli-seconds at different potential trigger points of Atrial fibrillation during the procedure.
Measured: 1 day
Number of patients with Changes in conduction time
Changes in conduction time is the changes in conduction of electrical impulses with caffeine during the procedure.
Measured: 1 day
Number of patients with Induction of Atrial Fibrillation/Atrial Tachycardia (AF/AT) or other arrhythmias
By infusing caffeine, intraprocedural for stimulation and detection of potential triggers of ablation, will caffeine infusion lead to the start of atrial fibrillation (AF), atrial tachycardia(AT) or any other arrhythmias.
Measured: 1 day
Number of patients with Identification of non-pulmonary triggers of AF
Identification of non-pulmonary triggers of AF
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2022
- Study startSep 2025 (estimated)
- Primary completionMar 2026 (estimated)
- Study completionJun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)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 N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The COFFEE-AF (How caffeine Induces Atrial Tachyarrhythmias) trial will be a multi-center, randomized, double-blinded trial of intravenous caffeine versus placebo among patients undergoing pulmonary vein isolation procedures for AF.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kansas City Heart Rhythm Research Foundation
- Sponsor type
- University, hospital or other
- Collaborators
- Kansas City Heart Rhythm Institute, Texas Cardiac Arrhythmia Institute, Austin, TX, USA, Loma Linda University
- Responsible party
- Sponsor
- Investigators
- Dhanunjaya Lakkireddy, Principal investigator, Kansas City Heart Rhythm Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05464940
- Sponsor's protocol ID
- KCHRRF-COFFEE AF-0012
- Status last verified
- Oct 2024
- First submitted
- 5 Jul 2022
- Last updated
- 28 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
McCarthy DM, Mycyk MB, DesLauriers CA. Hospitalization for caffeine abuse is associated with abuse of other pharmaceutical products. Am J Emerg Med. 2008 Sep;26(7):799-802. doi: 10.1016/j.ajem.2007.10.018.
PubMed 18774047Chen Y, Parrish TB. Caffeine's effects on cerebrovascular reactivity and coupling between cerebral blood flow and oxygen metabolism. Neuroimage. 2009 Feb 1;44(3):647-52. doi: 10.1016/j.neuroimage.2008.09.057. Epub 2008 Oct 19.
PubMed 19000770Temple JL. Caffeine use in children: what we know, what we have left to learn, and why we should worry. Neurosci Biobehav Rev. 2009 Jun;33(6):793-806. doi: 10.1016/j.neubiorev.2009.01.001. Epub 2009 Jan 20.
PubMed 19428492Reissig CJ, Strain EC, Griffiths RR. Caffeinated energy drinks--a growing problem. Drug Alcohol Depend. 2009 Jan 1;99(1-3):1-10. doi: 10.1016/j.drugalcdep.2008.08.001. Epub 2008 Sep 21.
PubMed 18809264Wendt IR, Stephenson DG. Effects of caffeine on Ca-activated force production in skinned cardiac and skeletal muscle fibres of the rat. Pflugers Arch. 1983 Aug;398(3):210-6. doi: 10.1007/BF00657153.
PubMed 6634380Rashid A, Hines M, Scherlag BJ, Yamanashi WS, Lovallo W. The effects of caffeine on the inducibility of atrial fibrillation. J Electrocardiol. 2006 Oct;39(4):421-5. doi: 10.1016/j.jelectrocard.2005.12.007. Epub 2006 Aug 21.
PubMed 16919674Bodar V, Chen J, Gaziano JM, Albert C, Djousse L. Coffee Consumption and Risk of Atrial Fibrillation in the Physicians' Health Study. J Am Heart Assoc. 2019 Aug 6;8(15):e011346. doi: 10.1161/JAHA.118.011346. Epub 2019 Aug 5.
PubMed 31378120Larsson SC, Drca N, Jensen-Urstad M, Wolk A. Coffee consumption is not associated with increased risk of atrial fibrillation: results from two prospective cohorts and a meta-analysis. BMC Med. 2015 Sep 23;13:207. doi: 10.1186/s12916-015-0447-8.
PubMed 26394673Conen D, Chiuve SE, Everett BM, Zhang SM, Buring JE, Albert CM. Caffeine consumption and incident atrial fibrillation in women. Am J Clin Nutr. 2010 Sep;92(3):509-14. doi: 10.3945/ajcn.2010.29627. Epub 2010 Jun 23.
PubMed 20573799
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Intravenous Caffeine on Atrial Electrical Properties and Potential Arrythmia Induction in Patients With Paroxysmal Atrial Fibrillation: The COFFEE-AF Trial
- ClinicalTrials.gov ID
- NCT05464940
- Acronym / sponsor ID
- KCHRRF-COFFEE AF-0012
- Conditions
- Atrial Fibrillation
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Kansas City Heart Rhythm Research FoundationUniversity, hospital or other
- Collaborators
- Kansas City Heart Rhythm Institute, Texas Cardiac Arrhythmia Institute, Austin, TX, USA, Loma Linda University
- Study start
- Sep 2025 (estimated)
- Primary completion
- Mar 2026 (estimated)
- Study completion
- Jun 2026 (estimated)
- First posted
- 19 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This "How caffeine Induces Atrial Tachyarrhythmias" trial will be a multi-center, randomized, double-blinded trial of intravenous caffeine versus placebo among patients undergoing pulmonary vein isolation procedures for Atrial Fibrillation(AF).
Detailed description
The mechanism by which caffeine might change cardiac electrophysiologic properties is largely unknown. Most of the prior studies conducted have evaluated the correlation based on the premise of oral consumption. One caveat among such study designs can be underreporting or overreporting the amount of caffeine ingested. To this date, no clinical trials exist that has studied the in vivo effects of caffeine to assess the atrial refractory period and conduction velocity and its potential to cause atrial or ventricular ectopy or sustained arrythmia induction including Atrial Tachycardia(AT)/Atrial Fibrillation(AF)/Ventricular Tachycardia(VT)/Ventricular Fibrillation(VF). As it is hypothesized that decreasing the atrial refractory period can render atria more prone to fibrillation. The pulmonary veins have proven integral to AF pathophysiology, the relationship between pulmonary vein electrophysiology and lifestyle factors in particular has not previously been assessed. It is also not clear if caffeine increases the risk of AF on those patients with known AF diagnosis. To bridge this gap, a randomized controlled trial is proposed to assess the effects of intravenous caffeine on atrial activity during AF ablation procedures.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- The COFFEE-AF (How caffeine Induces Atrial Tachyarrhythmias) trial will be a multi-center, randomized, double-blinded trial of intravenous caffeine versus placebo among patients undergoing pulmonary vein isolation procedures for AF.
| Arm | Type | Receives |
|---|---|---|
| Group assigned to receive caffeine | Active comparator | Other: Intravenous caffeine |
| Group assigned to receive masked placebo | Placebo comparator | Other: Masked Placebo |
Who may qualify
- Ages
- 21 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- All adult patients from 21-90 years of age with new onset Paroxysmal Atrial Fibrillation presenting in sinus rhythm or AF of recent onset (the latter confirmed by sinus rhythm documented no more than 1 week prior) undergoing AF ablation will be included in the study.
Key exclusion criteria (9 listed)
- History of substance abuse or alcoholism.
- Left ventricular ejection fraction <50%.
- Liver dysfunction.
- Pregnancy.
- Inability to give informed consent.
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 |
|---|---|---|
| Intravenous caffeineGroup assigned to receive caffeine will receive intravenous(IV) caffeine and sodium benzoate infusion starting at 250-500 mg. This method will use an automated algorithm that adjusts the flow of the infusion depending on the individual's sex and weight and then in a serial fashion in response to blood caffeine measurements. Serial blood caffeine measurements at pre-determined intervals according to the algorithm will be until a steady state is obtained. | Other | Group assigned to receive caffeine |
| Masked PlaceboThe patients assigned to the masked placebo will receive 5% dextrose in 0.45% saline using the same infusion protocol for a random length of time that was within 1 standard deviation(SD) of the mean time to achieve a steady state using the caffeine protocol (17+4 min). To maintain blinding, caffeine blood concentration measurements that will be randomly generated within 2 SDs of the predicted values calculated by the algorithm will be used and verbally communicated for placebo infusions. | Other | Group assigned to receive masked placebo |
Primary outcome
Number of Participants With Atrial Fibrillation Induction
Time frame: 1 day
Induction of Atrial fibrillation will be attempted by pacing and isoproterenol infusion following study drug infusion. The ability to induce atrial fibrillation (yes or no) will be recorded as the primary outcome.
4 secondary outcomes
Number of patients with Site-specific changes in AERP(Atrial Effective Refractory Period)
Time frame: 1 day
Number of patients with Changes in conduction time
Time frame: 1 day
Number of patients with Induction of Atrial Fibrillation/Atrial Tachycardia (AF/AT) or other arrhythmias
Time frame: 1 day
Number of patients with Identification of non-pulmonary triggers of AF
Time frame: 1 day
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2025.
- Background: PubMed 18774047McCarthy DM, Mycyk MB, DesLauriers CA. Hospitalization for caffeine abuse is associated with abuse of other pharmaceutical products. Am J Emerg Med. 2008 Sep;26(7):799-802. doi: 10.1016/j.ajem.2007.10.018.
- Background: PubMed 19000770Chen Y, Parrish TB. Caffeine's effects on cerebrovascular reactivity and coupling between cerebral blood flow and oxygen metabolism. Neuroimage. 2009 Feb 1;44(3):647-52. doi: 10.1016/j.neuroimage.2008.09.057. Epub 2008 Oct 19.
- Background: PubMed 19428492Temple JL. Caffeine use in children: what we know, what we have left to learn, and why we should worry. Neurosci Biobehav Rev. 2009 Jun;33(6):793-806. doi: 10.1016/j.neubiorev.2009.01.001. Epub 2009 Jan 20.
- Background: PubMed 18809264Reissig CJ, Strain EC, Griffiths RR. Caffeinated energy drinks--a growing problem. Drug Alcohol Depend. 2009 Jan 1;99(1-3):1-10. doi: 10.1016/j.drugalcdep.2008.08.001. Epub 2008 Sep 21.
- Background: PubMed 6634380Wendt IR, Stephenson DG. Effects of caffeine on Ca-activated force production in skinned cardiac and skeletal muscle fibres of the rat. Pflugers Arch. 1983 Aug;398(3):210-6. doi: 10.1007/BF00657153.
- Background: PubMed 16919674Rashid A, Hines M, Scherlag BJ, Yamanashi WS, Lovallo W. The effects of caffeine on the inducibility of atrial fibrillation. J Electrocardiol. 2006 Oct;39(4):421-5. doi: 10.1016/j.jelectrocard.2005.12.007. Epub 2006 Aug 21.
- Background: PubMed 31378120Bodar V, Chen J, Gaziano JM, Albert C, Djousse L. Coffee Consumption and Risk of Atrial Fibrillation in the Physicians' Health Study. J Am Heart Assoc. 2019 Aug 6;8(15):e011346. doi: 10.1161/JAHA.118.011346. Epub 2019 Aug 5.
- Background: PubMed 26394673Larsson SC, Drca N, Jensen-Urstad M, Wolk A. Coffee consumption is not associated with increased risk of atrial fibrillation: results from two prospective cohorts and a meta-analysis. BMC Med. 2015 Sep 23;13:207. doi: 10.1186/s12916-015-0447-8.
- Background: PubMed 20573799Conen D, Chiuve SE, Everett BM, Zhang SM, Buring JE, Albert CM. Caffeine consumption and incident atrial fibrillation in women. Am J Clin Nutr. 2010 Sep;92(3):509-14. doi: 10.3945/ajcn.2010.29627. Epub 2010 Jun 23.
- Individual participant dataSharing planned: No
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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.
Dhanunjaya Lakkireddy principal investigator
Kansas City Heart Rhythm Institute
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intravenous caffeine in people with Atrial Fibrillation, run by Kansas City Heart Rhythm Research Foundation at 9 sites 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 9 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: status not confirmed, as of the sponsor's last update on 28 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Donita Atkins (816-651-1969, datkins@kchrf.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Atrial Fibrillation Induction (time frame: 1 day). 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 NCT05464940, which also lists 9 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 28 Aug 2025.