Fentanyl and Ticagrelor Interaction in Percutaneous Coronary Intervention

(FACTPCI Trial)

Overseen By Sudhakar Sattur, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: The Guthrie Clinic

Must not be taking: P2Y12 inhibitors, Anticoagulants

Disqualifiers: Pregnancy, Coagulation disorders, Renal impairment, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

38 Participants Needed

Trial Summary

What is the purpose of this trial?

During a percutaneous coronary intervention (PCI), Fentanyl is commonly used for sedation. Ticagrelor is also routinely used as anti-platelet agent during PCI. However, a recent study has demonstrated the decrease in effectiveness of Ticagrelor when administered along with Fentanyl. Hence this study was designed to further assess the interaction between crushed vs non crushed Ticagrelor and Fentanyl given during PCI procedures.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you've used P2Y12 inhibitors in the last 14 days or if you're on anticoagulants.

What data supports the idea that Fentanyl and Ticagrelor Interaction in Percutaneous Coronary Intervention is an effective drug?

The available research shows that Ticagrelor is a commonly used drug for heart conditions and is effective in reducing blood clots. One study compared Fentanyl and Morphine, two pain-relief drugs, and found that Fentanyl does not delay the action of Ticagrelor as much as Morphine does. This suggests that using Fentanyl with Ticagrelor might be more effective in heart procedures than using Morphine. Another study looked at Fentanyl and another pain-relief drug, Lignocaine, and found that both worked well with Ticagrelor in heart patients. These findings support the idea that Fentanyl and Ticagrelor together can be an effective treatment during heart procedures. ^{1 2 3 4 5}

What safety data exists for the interaction of Fentanyl and Ticagrelor in PCI?

The provided research primarily discusses the safety and effects of Ticagrelor, particularly its use in acute coronary syndromes and PCI. Ticagrelor is known to cause bradyarrhythmias and has a 'black box' warning for bleeding risks. There is no specific mention of Fentanyl or its interaction with Ticagrelor in the provided studies. Therefore, while there is safety data on Ticagrelor, specific data on its interaction with Fentanyl in PCI is not covered in the provided research. ^{1 2 3 6 7}

Is the drug Ticagrelor a promising treatment for patients undergoing Percutaneous Coronary Intervention?

Yes, Ticagrelor is a promising drug for patients undergoing Percutaneous Coronary Intervention because it is a commonly used oral medication that helps prevent blood clots by inhibiting platelet activity. This can be crucial in treating acute coronary syndrome and during procedures like PCI to ensure better blood flow and reduce the risk of heart attacks. ^{2 4 5 8 9}

Eligibility Criteria

This trial is for individuals undergoing a heart procedure called PCI and can swallow pills. It's not for pregnant people, those who've taken certain blood thinners recently, have bleeding disorders, low platelets, bad kidney or liver function, or are allergic to the study drugs.

Inclusion Criteria

I am scheduled for a procedure to open blocked arteries in my heart.

I can take pills by mouth.

Exclusion Criteria

You are pregnant.

I have had or am scheduled for a valve replacement in my heart via catheter.

Platelet count < 100,000/mm3

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Fentanyl and Ticagrelor during PCI to assess the interaction between crushed vs non-crushed Ticagrelor

1 day

1 visit (in-person)

Follow-up

Participants are monitored for platelet function after treatment

6 hours

Treatment Details

Interventions

• Fentanyl
• Ticagrelor

Trial Overview The study examines how well Ticagrelor works when given in crushed form versus whole tablets during PCI in patients also receiving Fentanyl for sedation. The goal is to see if crushing the pill affects its interaction with Fentanyl.

Participant Groups

Group I: Fentanyl and Crushed Ticagrelor Experimental Treatment 2 Interventions

Premedicated with Fentanyl (at least 25mcg by IV) followed by Ticagrelor 90mg tablet administered crushed (180 mg dose)

Group II: Fentanyl and Non-crushed Ticagrelor Active Control 2 Interventions

Premedicated with Fentanyl (at least 25mcg by IV) followed by Ticagrelor 90mg tablet administered as a whole tablet (180 mg dose)

Ticagrelor is already approved in United States, European Union for the following indications:

Approved in United States as Brilinta for:

• Acute coronary syndrome (ACS)
• Cardiovascular event prevention
• Coronary artery disease (CAD)
• Acute ischemic stroke
• Transient ischemic attack (TIA)

Approved in European Union as Brilique for:

• Acute coronary syndrome (ACS)
• Cardiovascular event prevention
• Coronary artery disease (CAD)
• Acute ischemic stroke
• Transient ischemic attack (TIA)

Who Is Running the Clinical Trial?

The Guthrie Clinic

Lead Sponsor

Trials

27

Recruited

1,700+

Findings from Research

In a study of 81 cardiac surgical patients, those who continued taking ticagrelor with acetylsalicylic acid (ASA) until surgery experienced significantly higher blood loss and required more blood product transfusions compared to those on clopidogrel with ASA.

Despite the increased bleeding and transfusion needs in the ticagrelor group, there were no significant differences in intensive care unit stay, hospital stay, or mortality rates, indicating that while ticagrelor may pose bleeding risks, it does not adversely affect overall survival or recovery in the short term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of cardiac surgery patients with ongoing ticagrelor therapy: boon and bane of a new drug. Schotola, H., Bräuer, A., Meyer, K., et al.[2018]

Ticagrelor is an effective oral antiplatelet medication commonly used in patients with acute coronary syndrome and after procedures like PCI, acting as a reversible inhibitor of the P2Y12 receptor.

Despite its efficacy, Ticagrelor can cause bradyarrhythmias and ventricular pauses, as demonstrated in a case study of a 58-year-old man who experienced syncope after loading with the drug, highlighting the need for monitoring its cardiac effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor-Induced Syncope/Bradyarrhythmia. Kotaru, V., Kalavakunta, JK.[2021]

Ticagrelor is a new type of P2Y(12) antagonist that works differently from traditional antiplatelet medications like clopidogrel and prasugrel, providing a potentially more effective option for treating acute coronary syndromes.

Clinical trials have shown that ticagrelor, when used with aspirin, has a favorable safety profile and can overcome some limitations associated with clopidogrel, making it a valuable addition to antiplatelet therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor: a P2Y12 antagonist for use in acute coronary syndromes. Wijeyeratne, YD., Joshi, R., Heptinstall, S.[2022]

In a study of 38 STEMI patients, fentanyl did not show improved platelet inhibition at 2 hours after ticagrelor loading compared to morphine, indicating similar initial effects on platelet reactivity.

However, at 4 hours, patients treated with fentanyl exhibited significantly lower platelet reactivity than those treated with morphine, suggesting that fentanyl may enhance the absorption and effectiveness of ticagrelor over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effects of fentanyl versus morphine on platelet inhibition induced by ticagrelor in patients with ST-segment elevation myocardial infarction: Full results of the PERSEUS randomized trial. Iglesias, JF., Valgimigli, M., Carbone, F., et al.[2022]

In a study of 70 patients undergoing coronary angiography, intravenous fentanyl significantly reduced the plasma levels and antiplatelet effects of ticagrelor compared to lignocaine, indicating that fentanyl may impair the effectiveness of ticagrelor in patients with unstable angina or non-ST-elevation myocardial infarction.

Both fentanyl and lignocaine were well tolerated and provided effective analgesia, but lignocaine did not affect the bioavailability or delay the antiplatelet effect of ticagrelor, suggesting it may be a better choice for procedural analgesia during coronary interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of lignocaine vs. opioids on antiplatelet activity of ticagrelor: the LOCAL trial. Fernando, H., Duong, T., Huynh, K., et al.[2022]

Ticagrelor (Brilinta™) was approved by the FDA for treating acute coronary syndromes based on the PLATO trial, which involved 18,624 patients and compared its efficacy to clopidogrel over 6-12 months.

Despite its approval, there were significant concerns from FDA reviewers regarding its efficacy and safety, particularly related to bleeding risks and the potential reduction in effectiveness when used with high doses of aspirin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor FDA approval issues revisited. Serebruany, VL.[2018]

In a study involving 29 healthy volunteers, the generic drug Ticaloguard® was found to have similar therapeutic effects and safety profiles compared to the brand-name drug Brilique® in terms of platelet aggregation, indicating that it can be used interchangeably in treating acute coronary syndrome.

The study emphasizes the importance of testing the therapeutic equivalence of generic drugs, especially for critical medications, rather than relying solely on bioequivalence, to ensure patient safety and effective treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testing P2Y12 platelet inhibitors generics beyond bioequivalence: a parallel single-blinded randomized trial. Zarif, B., Soliman, L., Sabry, NA., et al.[2022]

In a study of 70 patients undergoing PCI, it was found that higher doses and later timing of fentanyl administration significantly reduced the effectiveness of ticagrelor, a medication used to prevent blood clots, as indicated by lower ticagrelor concentrations and less platelet inhibition.

The results suggest that the impact of fentanyl on ticagrelor absorption and its antiplatelet effects is dose- and time-dependent, highlighting the importance of careful management of fentanyl during procedures involving ticagrelor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Dose and Timing of Fentanyl Impacts on Ticagrelor Absorption and Platelet Inhibition During Percutaneous Coronary Intervention: The PACIFY Randomized Clinical Trial. Goli, RR., Ibrahim, K., Shah, R., et al.[2020]

This study aims to compare the effects of intravenous fentanyl and morphine on the absorption and effectiveness of ticagrelor in patients with STEMI undergoing primary percutaneous coronary intervention, with a focus on pharmacokinetics and pharmacodynamics.

The primary endpoint will assess platelet reactivity at 2 hours after ticagrelor loading, providing insights into how fentanyl may influence the drug's action compared to morphine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of intravenous fentanyl compared with morphine on ticagrelor absorption and platelet inhibition in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: rationale and design of the PERSEUS randomized trial. Degrauwe, S., Roffi, M., Lauriers, N., et al.[2020]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of cardiac surgery patients with ongoing ticagrelor therapy: boon and bane of a new drug. [2018]

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

Ticagrelor-Induced Syncope/Bradyarrhythmia. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Ticagrelor: a P2Y12 antagonist for use in acute coronary syndromes. [2022]

4. Poland pubmed.ncbi.nlm.nih.gov

Comparative effects of fentanyl versus morphine on platelet inhibition induced by ticagrelor in patients with ST-segment elevation myocardial infarction: Full results of the PERSEUS randomized trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Effects of lignocaine vs. opioids on antiplatelet activity of ticagrelor: the LOCAL trial. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Ticagrelor FDA approval issues revisited. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Testing P2Y12 platelet inhibitors generics beyond bioequivalence: a parallel single-blinded randomized trial. [2022]

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

The Dose and Timing of Fentanyl Impacts on Ticagrelor Absorption and Platelet Inhibition During Percutaneous Coronary Intervention: The PACIFY Randomized Clinical Trial. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Influence of intravenous fentanyl compared with morphine on ticagrelor absorption and platelet inhibition in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: rationale and design of the PERSEUS randomized trial. [2020]