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

21 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal is to determine whether fentanyl and morphine have similar effects in reducing aspirin's effect upon platelets in emergency department patients with chest discomfort. Morphine has been shown to worsen outcomes in heart attack patients due to reduction of oral anti-platelet agent effectiveness and so many providers have switches to using fentanyl. However, it is largely unknown whether fentanyl has similar effects.

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 safety data available for Fentanyl and Morphine in humans?

The provided research articles do not contain specific safety data for Fentanyl or Morphine. Therefore, no relevant safety information is available from these articles. ^{1 2 3 4 5}

How does the drug Fentanyl differ from Morphine in affecting platelet reactivity?

The clinical trial compares Fentanyl and Morphine to see how they affect platelet reactivity, which is important for understanding their impact on blood clotting. This is unique because it focuses on the potential differences in how these drugs might influence platelet function, which is not typically the primary focus when these drugs are used for pain management. ^{6 7 8 9 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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 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 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]

References

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

Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Comparative safety of biologic versus conventional synthetic DMARDs in rheumatoid arthritis with COPD: a real-world population study. [2020]

3. Germany 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. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

Adverse effects of treatment with porcine factor VIII. [2004]

5. Germany pubmed.ncbi.nlm.nih.gov

Potentially thrombogenic materials in factor IX concentrates. [2013]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Different anticoagulants and platelet reactivity in cardiac surgical patients. [2019]

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

Effects of enoxaparin and unfractionated heparin on platelet activity and reactivity during carotid endarterectomy. [2017]

8. Poland pubmed.ncbi.nlm.nih.gov

Predictors of high platelet reactivity during aspirin treatment in patients with type 2 diabetes. [2015]

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

Attenuation of platelet reactivity by enoxaparin compared with unfractionated heparin in patients undergoing haemodialysis. [2006]

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

Comparison of Commercially Available Blood Collection Tubes Containing Sodium Citrate and Hirudin in Platelet Aggregation Testing. [2019]