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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two forms of the drug Ticagrelor (also known as Brilinta, Brilique, or Possia) interact with Fentanyl (also known as Sublimaze, Actiq, Duragesic, Fentora, Abstral, or Onsolis) during percutaneous coronary interventions (PCI). Researchers aim to determine if crushed Ticagrelor works differently than the whole tablet when taken with Fentanyl, which helps patients relax during PCI. This study may suit individuals who need a PCI and can take oral medications. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective treatment benefits more patients.

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 is the safety track record for Fentanyl and Ticagrelor?

Research has shown that fentanyl, a drug often used to help patients relax during heart procedures, can make ticagrelor, a medicine that prevents blood clots, less effective. This interaction raises safety concerns. Specifically, studies indicate that fentanyl slows down how quickly ticagrelor can stop platelets (tiny blood cells) from clumping together. However, no specific reports exist of fentanyl causing serious harm when used in this way.

Ticagrelor is already approved for preventing blood clots in heart patients, meaning it has undergone safety testing in humans. The main concern is the decreased effectiveness of ticagrelor when used with fentanyl, rather than any direct harm from the drugs themselves.

Overall, both drugs are generally well-tolerated on their own, but their interaction may affect how well ticagrelor works during procedures. Potential trial participants should be aware of this interaction. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this trial because it's exploring how fentanyl interacts with ticagrelor during percutaneous coronary intervention (PCI), a procedure to treat narrowed coronary arteries. Normally, ticagrelor is given whole, but this study looks at whether crushing the tablet affects its efficiency, especially when premedicated with fentanyl. This approach could enhance the speed and effectiveness of ticagrelor's action in patients undergoing PCI, potentially leading to better and quicker protection against blood clots compared to the traditional whole-tablet administration. Understanding this interaction may refine treatment protocols and improve patient outcomes during critical heart procedures.

What evidence suggests that this trial's treatments could be effective for percutaneous coronary intervention?

This trial will compare the interaction of Fentanyl with Ticagrelor in two forms during percutaneous coronary intervention (PCI). Research has shown that Ticagrelor effectively prevents blood clots during procedures like PCI, which helps open blocked heart arteries. However, using Ticagrelor with Fentanyl can reduce its effectiveness. Specifically, Ticagrelor is less able to prevent blood cells from clumping together when combined with Fentanyl. Research has confirmed this interaction, finding that higher doses of Fentanyl make Ticagrelor less effective. In this trial, one arm will receive Fentanyl and crushed Ticagrelor, while another will receive Fentanyl and non-crushed Ticagrelor. Previous studies found no significant difference in Ticagrelor's effectiveness when using crushed versus whole tablets with Fentanyl. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

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

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

You are pregnant.

Platelet count < 100,000/mm3

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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]

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]

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 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]

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]

Citations

1. frontiersin.org frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2024.1324641/full

Differential impact of fentanyl and morphine doses on ... Higher doses of morphine have been shown to significantly reduce ticagrelor absorption and attenuate its antiplatelet effects as compared to ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03476369

NCT03476369 | Fentanyl and Crushed Ticagrelor in ... However, a recent study has demonstrated the decrease in effectiveness of Ticagrelor when administered along with Fentanyl. Hence this study was designed to ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11018886/

Differential impact of fentanyl and morphine doses on ... We found a dose-dependent relationship between the administration of intravenous fentanyl, but not morphine, and ticagrelor-induced platelet inhibition.

4. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.038317

Platelet Inhibition With Cangrelor and Crushed Ticagrelor ... Cangrelor is an effective strategy to bridge the gap in platelet inhibition associated with the use of oral P2Y 12 inhibition induced by ticagrelor.

5. scai.org scai.org/fact-fentanyl-and-crushed-ticagrelor-pci-trial-coverage-crt-2025

FACT (Fentanyl and Crushed Ticagrelor) PCI Trial In this single center randomized control trial done on thirty-eight patients undergoing PCI, there was no significant difference in the antiplatelet efficacy.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S155171441730681X

Effect of intravenous fentanyl on ticagrelor absorption and ... The PACIFY study will test whether intravenous fentanyl also impairs the absorption and action of oral P2Y 12 inhibitors.

7. ahajournals.org ahajournals.org/doi/10.1161/circulationaha.117.031678

Effect of Intravenous Fentanyl on Ticagrelor Absorption and ... The question of whether fentanyl could have adverse consequences in patients undergoing percutaneous coronary intervention (PCI) is raised ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6202927/

Fentanyl Delays the Platelet Inhibition Effects of Oral ... The assumption that fentanyl is safe for PCI is challenged by recent research demonstrating an interaction between intravenous morphine and oral P2Y 12 platelet ...