Fentanyl vs. Morphine for Platelet Reactivity

Overseen By Monique Luna

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Spectrum Health - Lakeland

Must not be taking: Aspirin, Clopidogrel, Anticoagulants, Narcotics

Disqualifiers: Pregnancy, EMS arrival, 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

Compensation: Varies

Number of Visits: 1

Duration: 2 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether fentanyl (a narcotic pain medication) and morphine affect aspirin's effectiveness on platelets in individuals experiencing chest discomfort in the emergency department. Morphine is known to reduce aspirin's effectiveness for heart attack patients, so researchers seek to determine if fentanyl causes similar issues. Participants will be divided into three groups: those receiving morphine, those receiving fentanyl, and a control group not receiving any narcotics. Suitable candidates have recently visited the emergency department with chest pain, arrived by private vehicle, and received aspirin within 30 minutes of a blood draw. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical discoveries.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are already on aspirin, clopidogrel, or stronger blood thinners.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both fentanyl and morphine, the treatments under study, have known safety concerns. Studies have found that fentanyl can cause serious side effects like respiratory depression, which can dangerously slow or stop breathing. This risk increases with large doses or in individuals not accustomed to strong pain medications.

Morphine, in contrast, has been linked to increased platelet reactivity, affecting blood clotting in heart patients and potentially worsening outcomes during heart attacks. Like fentanyl, it also carries the risk of severe breathing problems.

Both drugs are strong opioids, effective for pain relief but requiring careful use due to potential side effects. Previous patients have demonstrated that these drugs can be managed safely, but monitoring for adverse effects is crucial. Participants in clinical trials like this one help researchers better understand these risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they are exploring how fentanyl and morphine, two powerful narcotics, affect platelet reactivity. This is particularly intriguing since most pain management options, like other opioids or non-opioid analgesics, do not specifically focus on platelet function. Fentanyl is known for its rapid action and potent pain relief, potentially offering faster effects than traditional morphine. By comparing these two drugs, the trial aims to uncover how each impacts platelet activity, which could lead to more informed choices in pain management, especially for patients at risk of clotting issues.

What evidence suggests that fentanyl and morphine could be effective for platelet reactivity in chest discomfort?

This trial will compare the effects of fentanyl and morphine on platelet reactivity. Research has shown that fentanyl might slow the absorption of certain blood-thinning medications, like ticagrelor, potentially delaying their ability to prevent blood clots in individuals with heart problems. Conversely, studies have found that morphine can reduce the effectiveness of these blood-thinning drugs, posing risks for heart attack patients. Due to these concerns, many doctors prefer fentanyl over morphine to avoid negative effects. Both drugs affect platelets, but fentanyl might have a less harmful impact than morphine. However, further research is needed to fully understand fentanyl's effects on platelets. Participants in this trial will receive either fentanyl, morphine, or be part of a control group not receiving any narcotics. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults in the emergency department with chest discomfort who are undergoing specific heart tests, have taken aspirin recently, and arrived by private vehicle. It's not for those already on certain blood thinners, pregnant women, chronic narcotic users, non-English speakers or anyone previously enrolled.

Inclusion Criteria

I took aspirin within 30 minutes before my first blood test.

Adult Emergency Department patients undergoing 0 and 2 hour troponin testing

Provide informed consent

Exclusion Criteria

Patients not expected to get a 2 hour troponin

Pregnant patients

Patients on chronic narcotics

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants receive aspirin and are administered either morphine, fentanyl, or no narcotics. Platelet aggregation studies are conducted at zero and two hours.

2 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Fentanyl
• Morphine

Trial Overview The study is looking at how fentanyl and morphine affect the way aspirin works on platelets in patients with chest pain. Researchers want to see if fentanyl might be a better option than morphine because of potential negative effects associated with morphine.

How Is the Trial Designed?

Group I: Morphine Experimental Treatment 1 Intervention

the second group will be those receiving morphine

Group II: Fentanyl Experimental Treatment 1 Intervention

the 3rd group will be those receiving fentanyl

Group III: Control Active Control 1 Intervention

not receiving any narcotics

Fentanyl is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Fentanyl for:

• Pain management
• Anesthesia

Approved in European Union as Fentanyl for:

• Severe pain
• Breakthrough pain in cancer patients

Approved in Canada as Fentanyl for:

• Pain relief
• Neuropathic pain

Approved in Japan as Fentanyl for:

• Cancer pain
• Postoperative pain

Who Is Running the Clinical Trial?

Spectrum Health - Lakeland

Lead Sponsor

Trials

14

Recruited

1,300+

Published Research Related to This Trial

In a study involving 290 cardiac surgical patients, low-molecular-weight heparin showed a significantly lower rate of severe platelet inhibition compared to unfractionated heparin, suggesting it may be safer for maintaining platelet function during surgery.

The findings indicate that low-molecular-weight heparin could potentially reduce blood loss during cardiopulmonary bypass, although the exact clinical implications require further investigation due to unknown appropriate dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Different anticoagulants and platelet reactivity in cardiac surgical patients. John, LC., Rees, GM., Kovacs, IB.[2019]

In a study involving 20 patients undergoing haemodialysis, enoxaparin was found to significantly reduce platelet reactivity compared to unfractionated heparin (UFH), suggesting a safer anticoagulation option.

Lower platelet reactivity with enoxaparin may lead to a reduced risk of adverse cardiac events in patients with end-stage renal disease, highlighting its potential benefits during haemodialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attenuation of platelet reactivity by enoxaparin compared with unfractionated heparin in patients undergoing haemodialysis. Aggarwal, A., Whitaker, DA., Rimmer, JM., et al.[2006]

In a study involving 20 healthy volunteers, sodium citrate was found to be a suitable anticoagulant for routine platelet function testing, as it did not significantly affect platelet counts or ADP-induced aggregation compared to hirudin.

However, hirudin-treated platelets showed significantly weaker aggregation responses with various agonists, suggesting that sodium citrate remains the preferred choice, although the time constraints of using it in testing warrant further exploration of alternative anticoagulants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Commercially Available Blood Collection Tubes Containing Sodium Citrate and Hirudin in Platelet Aggregation Testing. Janse van Rensburg, WJ., van der Merwe, P.[2019]

Concizumab, a once-daily subcutaneous treatment, showed promising long-term safety and efficacy in reducing bleeding rates in patients with hemophilia A and B, with annualized bleeding rates of 4.8 and 6.4 in the respective trials.

The treatment was generally well-tolerated, with most adverse events being mild and no serious thromboembolic events reported, although 25% of patients developed low-titer, transient anti-drug antibodies without significant clinical effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors. Shapiro, AD., Angchaisuksiri, P., Astermark, J., et al.[2022]

In a study involving 7424 rheumatoid arthritis patients with chronic obstructive pulmonary disease (COPD), biologic and targeted synthetic DMARDs (including abatacept) did not show an increased risk of adverse respiratory events compared to conventional synthetic DMARDs.

The analysis revealed that the risk of hospitalized COPD exacerbations and other respiratory issues was similar between patients using biologic/tsDMARDs and those using csDMARDs, suggesting that these newer treatments are safe for patients with COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative safety of biologic versus conventional synthetic DMARDs in rheumatoid arthritis with COPD: a real-world population study. Hudson, M., Dell'Aniello, S., Shen, S., et al.[2020]

Factor XI concentrates derived from human plasma may contain significant amounts of potentially thrombogenic materials, raising concerns about their safety when used therapeutically.

In both in vitro and in vivo assays, a strong correlation (0.77) was found in the thrombogenicity of concentrates without heparin, indicating that these tests can reliably assess the risk of thrombosis associated with these products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potentially thrombogenic materials in factor IX concentrates. Kingdon, HS., Lundblad, RL., Veltkamp, JJ., et al.[2013]

In a study of 20 symptomatic patients undergoing carotid endarterectomy, both unfractionated heparin (UFH) and enoxaparin were found to increase platelet activity during surgery, as indicated by elevated levels of CD41 and CD62p.

Patients treated with UFH showed a significant increase in platelet-leukocyte aggregates (PLAs) after the procedure, suggesting that PLAs could serve as a useful measure for assessing platelet activity in surgical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of enoxaparin and unfractionated heparin on platelet activity and reactivity during carotid endarterectomy. Assadian, A., Senekowitsch, C., Hagmüller, GW., et al.[2017]

In a study of 171 patients with type 2 diabetes mellitus (DM2) on long-term aspirin therapy, there was significant variability in platelet reactivity, indicating that not all patients respond similarly to treatment.

Independent predictors of high platelet reactivity included chronic heart failure, current smoking, and higher leukocyte counts, suggesting that these factors may influence the effectiveness of aspirin in managing platelet function in DM2 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of high platelet reactivity during aspirin treatment in patients with type 2 diabetes. Kapłon-Cieślicka, A., Rosiak, M., Postuła, M., et al.[2015]

In a study involving 58 haemophilia A patients undergoing 65 surgical procedures, the newly developed recombinant FVIII (rAHF-PFM) demonstrated 100% efficacy in preventing bleeding complications during and after surgery, regardless of whether it was administered via bolus or continuous infusion.

rAHF-PFM was found to be safe and well-tolerated, with no FVIII inhibitors detected, indicating it is a non-immunogenic option for perioperative hemostatic management in patients with a history of FVIII exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical evaluation of a recombinant factor VIII prepared using a plasma/albumin-free method: efficacy and safety of Advate in previously treated patients. Négrier, C., Shapiro, A., Berntorp, E., et al.[2018]

In a study involving 25 hemophiliacs and 5 patients with autoantibodies, porcine FVIII was generally effective but led to a high rate of adverse effects, with 47% of treatment courses resulting in complications.

Severe thrombocytopenia occurred in 16% of courses, and allergic reactions were common, affecting 50% of patients, including severe anaphylactoid reactions in some cases, indicating that caution is needed when considering porcine FVIII for home treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects of treatment with porcine factor VIII. Gringeri, A., Santagostino, E., Tradati, F., et al.[2004]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0167527321002904

Comparison of the effect of Morphine and Fentanyl in ... The primary outcome was the difference in the maximal inhibition of platelet aggregation [IPA(%)] between the groups at 2 h. Pain relief, and drug-related ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9273249/

Comparative effects of fentanyl versus morphine on platelet ... Recently, fentanyl has been shown to reduce ticagrelor absorption and delay platelet inhibition compared with placebo in patients with chronic coronary syndrome ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05367336

Platelet Reactivity With Fentanyl, Morphine, or no Narcotic The goal is to determine whether fentanyl and morphine have similar effects in reducing aspirin's effect upon platelets in emergency department patients with ...

4. link.springer.com link.springer.com/article/10.1007/s43440-023-00447-7

Interactions of fentanyl with blood platelets and plasma ... A series of in vitro experiments was performed to investigate the ability of fentanyl to activate platelets, potentiate platelet response to ADP, and/or ...

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

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.

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

Fentanyl Delays the Platelet Inhibition Effects of Oral ... Abstract. Morphine delays oral P2Y 12 platelet inhibitor absorption and is associated with adverse outcomes after myocardial infarction.

7. nature.com nature.com/articles/s41398-019-0625-0

The rising crisis of illicit fentanyl use, overdose, and ... Respiratory depression is the most dangerous adverse reaction to fentanyl that can result in lethality. In rats, intravenous injections of ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4902689/

Safety of fentanyl initiation according to past opioid exposure ... Results: We identified 11 063 patients who began using fentanyl patches during the study period. Overall, fentanyl initiation was deemed unsafe in 74.1% of ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S152659000167915X

Evaluation of long-term efficacy and safety of transdermal ... Long-term treatment with TDF provided a stable degree of pain control in the majority of patients with moderate to severe chronic noncancer pain.