Adenosine for Premature Ventricular Contractions

Overseen By James Ip

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Weill Medical College of Cornell University

Must not be taking: Anti-arrhythmic drugs

Disqualifiers: Structural heart disease, Coronary artery disease, Asthma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

100 Participants Needed

Trial Summary

What is the purpose of this trial?

Unblinded, controlled, non-randomized, mechanistic study to determine whether physiological mechanisms underlying PVC are sensitive to adenosine. One hundred subjects undergoing clinically-indicated, standard-of-care cardiac electrophysiology study (EPS) procedure for PVCs will receive adenosine and/or verapamil to learn if their arrhythmias are inducible similarly to sustained ventricular tachycardia.

Will I have to stop taking my current medications?

The trial requires that participants are not currently being treated with anti-arrhythmic drugs, so you would need to stop taking those medications to join.

Is adenosine generally safe for use in humans?

Adenosine is generally considered safe for use in humans, with common side effects like facial flushing, shortness of breath, and chest pressure being brief and not serious. However, rare but serious reactions like heart block, severe allergic reactions, and life-threatening heart rhythm changes have been reported, especially in patients with heart conditions. ^{1 2 3 4 5}

How does the drug adenosine differ from other treatments for premature ventricular contractions?

Adenosine is unique because it is an injectable drug with a very short half-life, meaning it works quickly and its effects wear off rapidly. It is primarily used for treating certain types of fast heart rhythms, and its rapid action and short duration make it different from other treatments that might have longer-lasting effects. ^{3 6 7 8 9}

Research Team

James E Ip, M.D

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

This trial is for adults aged 18-70 with premature ventricular contractions (PVCs) who are scheduled for an electrophysiology study and potential cardiac ablation. Participants must be able to consent and not on anti-arrhythmic drugs, pregnant, have structural heart disease, significant coronary artery blockage, or asthma if adenosine is used.

Inclusion Criteria

I am between 18 and 70 years old.

I understand the study and can agree to participate.

I am scheduled for a procedure to correct heart rhythm issues caused by PVCs.

Exclusion Criteria

You have asthma and are going to be given adenosine.

I have severe narrowing (70% or more) in my heart's arteries.

Pregnant

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a cardiac electrophysiology study (EPS) procedure, receive Verapamil to slow the heart, and then receive Adenosine to study its effects on PVCs.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including analysis of Holter monitor data.

4 weeks

Treatment Details

Interventions

• Adenosine

Trial Overview The study tests whether the physiological mechanisms causing PVCs respond to adenosine. It's an unblinded, controlled study involving 100 subjects already undergoing standard cardiac EPS procedures for PVCs. They will receive adenosine and/or verapamil to see if their arrhythmias can be induced like sustained ventricular tachycardia.

Participant Groups

Group I: Adenosine/ Verapamil Arm Experimental Treatment 1 Intervention

Adenosine: 0.84 mg/kg IV (140 mcg/kg/minute IV for 6 minutes) Verapamil: 0.15 mg/kg IV Adenosine is known to terminate ventricular arrhythmias that are due to triggered activity (ref Lerman). To study the effects of adenosine on PVC, the investigators will administer Verapamil to slow down the heart initially and adenosine after catheters are introduced to patients who are being treated for symptomatic PVC and have consented to treatment with an invasive electrophysiology study and catheter ablation.

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Findings from Research

Adenosine is effective in terminating supraventricular tachycardias by slowing conduction through the AV node, making it a valuable tool in emergency settings for managing arrhythmias.

While adenosine is generally considered safe due to its short half-life and minimal serious side effects, this case highlights a potential risk of non-sustained polymorphic ventricular tachycardia following its administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adenosine-induced non-sustained polymorphic ventricular tachycardia. Romer, M., Candinas, R.[2019]

Adenosine effectively terminated paroxysmal supraventricular tachycardia (PSVT) in 36.4% of patients and helped diagnose unclear PSVT types in 47.7% of cases, demonstrating its utility in managing arrhythmias.

While subjective complaints were common after administration (80.6% of patients), they were short-lived and not clinically significant, indicating that adenosine is safe with no relevant complications observed in the study of 62 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness and safety of adenosine in the therapy and diagnosis of arrhythmias]. Dúbrava, J., Jurkovicová, O.[2022]

Adenosine is an approved treatment for paroxysmal supraventricular tachycardia, known for its very short half-life of 10 seconds and common but transient side effects like facial flushing and dyspnea.

This report highlights a unique case of a prolonged anaphylactoid reaction in an elderly woman after adenosine administration, marking the first documented instance of such a reaction, which required additional pharmacological intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anaphylactoid reaction to adenosine. Fata, JG., Roth, RN., Carpenter, L.[2019]

Adenoscan injection (adenosine) was found to be safe for use in patients unable to exercise, with an overall adverse drug reaction (ADR) rate of 16.0%, most of which were mild and resolved quickly without treatment.

The efficacy of Adenoscan for myocardial perfusion scintigraphy was high, with a success rate of 97.9% in 2,150 patients, making it a valuable tool for detecting ischemic heart disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The drug use results survey of Adenoscan injection 60 mg]. Hikita, A., Okita, Y., Kawai, M., et al.[2017]

Regadenoson, a selective A2A receptor agonist used for myocardial perfusion imaging, has been shown to have equivalent diagnostic accuracy for coronary artery disease compared to adenosine, with fewer serious side effects in multicenter trials.

However, recent cases indicate that regadenoson may carry a higher risk of life-threatening bradycardia, including asystole, than previously recognized, emphasizing the need for caution and monitoring in patients receiving this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asystole following regadenoson infusion in stable outpatients. Rosenblatt, J., Mooney, D., Dunn, T., et al.[2021]

Regadenoson is an effective pharmacologic stress agent for myocardial perfusion imaging, showing noninferior agreement in detecting reversible perfusion defects compared to adenosine in two phase III trials involving patients with coronary artery disease.

It is generally well tolerated, with most side effects resolving within about 15 minutes, and no unexpected ECG changes were observed, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regadenoson. Garnock-Jones, KP., Curran, MP.[2022]

Adenosine (Adenocard) is an injectable medication specifically used for the acute treatment of paroxysmal supraventricular tachycardia (PSVT), including cases linked to Wolff-Parkinson-White syndrome.

Despite its effectiveness in treating PSVT, many physicians remain unfamiliar with how adenosine works, its indications, and potential side effects, highlighting a need for increased awareness and education about this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical use of adenosine. Geraets, D., Kienzle, M.[2013]

Regadenoson, a selective A(2A) adenosine receptor agonist, shows promise as a pharmacologic stress agent for myocardial perfusion imaging, producing rapid and sustained hyperemia, which is beneficial for imaging procedures.

Unlike traditional vasodilators like adenosine and dipyridamole, which activate multiple adenosine receptor subtypes leading to undesirable effects, regadenoson selectively targets the A(2A) receptor, potentially reducing side effects and improving patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The future of pharmacologic stress: selective A2A adenosine receptor agonists. Cerqueira, MD.[2015]

Regadenoson and binodenoson, two selective adenosine A2A receptor agonists, show promise as safer alternatives to traditional pharmacologic stress agents like dipyridamole and adenosine, with ongoing Phase III studies evaluating their efficacy.

Both regadenoson and binodenoson demonstrated similar effectiveness to adenosine in detecting ischemia during single-photon emission CT imaging, while exhibiting a lower incidence of serious side effects such as atrioventricular block or bronchospasm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in pharmacologic agents in imaging: new A2A receptor agonists. Cerqueira, MD.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Adenosine-induced non-sustained polymorphic ventricular tachycardia. [2019]

2. Czech Republic pubmed.ncbi.nlm.nih.gov

[Effectiveness and safety of adenosine in the therapy and diagnosis of arrhythmias]. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Anaphylactoid reaction to adenosine. [2019]

4. Japan pubmed.ncbi.nlm.nih.gov

[The drug use results survey of Adenoscan injection 60 mg]. [2017]

5. United States pubmed.ncbi.nlm.nih.gov

Asystole following regadenoson infusion in stable outpatients. [2021]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Regadenoson. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Clinical use of adenosine. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

The future of pharmacologic stress: selective A2A adenosine receptor agonists. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

Advances in pharmacologic agents in imaging: new A2A receptor agonists. [2019]