Low-Dose Aspirin Dosing for Blood Clot Prevention After Surgery

Overseen By Ramakanth Yakkanti, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Miami

Must be taking: Aspirin

Must not be taking: Anticoagulants, NSAIDs

Disqualifiers: VTE history, Malignancy, BMI > 40, 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 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

5478 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is attempting to answer the question of whether 81 mg aspirin once daily is as effective as 81 mg aspirin twice daily in preventing blood clots after total joint replacement surgery.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on blood thinners or have a condition that requires anticoagulation, you may not be eligible to participate.

What data supports the effectiveness of the drug for preventing blood clots after surgery?

Research shows that low-dose aspirin (100 mg daily) effectively prevents blood clots by inhibiting platelet function, which is crucial for clot formation. In a study, 90% of patients taking aspirin had open grafts after surgery compared to 68% in the placebo group, indicating its effectiveness in maintaining blood flow. ^{1 2 3 4 5}

Is low-dose aspirin safe for humans?

Low-dose aspirin (100 mg daily) has been shown to be safe in humans, with no reported side effects in studies, and it effectively reduces blood clotting without increasing bleeding risks significantly. ^{2 3 4 5 6}

How does low-dose aspirin differ from other drugs for preventing blood clots after surgery?

Low-dose aspirin is unique because it effectively prevents blood clots by inhibiting platelet function with a lower risk of side effects, as it requires only a small daily dose (around 100 mg) to achieve full efficacy. This makes it safer and more convenient compared to higher doses or other treatments that might have more side effects. ^{2 3 4 6 7}

Research Team

Victor H Hernandez, MD

Principal Investigator

University of Miami

Eligibility Criteria

This trial is for adults over 18 who are about to have hip or knee replacement surgery and can understand the consent form. It's not for those with a history of blood clots, cancer, mental illness, extreme obesity (BMI > 40), pregnancy, or conditions that make aspirin use unsafe.

Inclusion Criteria

I am scheduled for a first-time hip or knee replacement surgery.

Exclusion Criteria

I need blood thinners for a condition I already have.

My BMI is over 40.

Pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 81 mg aspirin once or twice daily starting the night before surgery and continuing for up to 28 days post-surgery

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including incidence of thromboembolic events and adverse events

90 days

Treatment Details

Interventions

• Aspirin

Trial Overview The study is testing if taking low-dose aspirin once a day is just as good at preventing blood clots after joint replacement surgery as taking it twice a day. Participants will receive either one or two doses daily.

Participant Groups

Group I: Treatment Once Daily Experimental Treatment 1 Intervention

Participant receives 81 mg aspirin taken once daily beginning the night before surgery and up to 28 days post surgery.

Group II: Treatment Twice Daily Active Control 1 Intervention

Participant receives 81 mg aspirin taken twice daily (one in the morning and one at night) beginning at the night before surgery and up to 28 days post surgery.

Aspirin is already approved in European Union, United States, Canada, China for the following indications:

Approved in European Union as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in United States as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in Canada as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in China as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Findings from Research

In a study of 36 high-risk patients undergoing major non-cardiac surgery, low-dose acetylsalicylic acid (aspirin) significantly reduced platelet function both before and after surgery compared to a placebo, indicating its effectiveness in inhibiting platelet aggregation.

The study found that while platelet function decreased in the placebo group postoperatively, it remained consistently low in the aspirin group, suggesting that aspirin maintains its antiplatelet effect throughout the perioperative period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platelet function assessed by whole-blood aggregometry in patients undergoing non-cardiac surgery. Oscarsson, A., Öster, S., Fredrikson, M., et al.[2013]

In a study involving healthy volunteers who took varying doses of acetylsalicylic acid (ASA) for one week, all doses significantly inhibited platelet function and increased bleeding times, indicating its effectiveness in thrombosis prophylaxis.

The research found that a daily dose of around 100 mg of ASA maximized the effects on platelet function and bleeding time, suggesting that higher doses do not provide additional benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of different doses of some acetylsalicylic acid formulations on platelet function and bleeding times in healthy subjects. McLeod, LJ., Roberts, MS., Cossum, PA., et al.[2019]

A study involving 46 healthy participants demonstrated that a novel 75 mg soft-gel capsule formulation of acetylsalicylic acid (ASA) is non-inferior to a marketed powder solution in reducing serum thromboxane B2 (TXB2), a marker for platelet aggregation.

Both formulations showed similar effectiveness in inhibiting TXB2, with no reported adverse events, suggesting that the soft-gel capsule could be a safe and effective alternative for preventing cardiovascular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamics and pharmacokinetics of a novel, low-dose, soft-gel capsule of acetylsalicylic acid in comparison with an oral solution after single-dose administration to healthy volunteers: a phase I, two-way crossover study. Loprete, L., Leuratti, C., Scarsi, C., et al.[2021]

In a study of 83 patients, daily aspirin (100 mg) significantly improved graft patency rates after aortocoronary bypass surgery, with 90% of grafts patent in the aspirin group compared to 68% in the placebo group at four months.

Aspirin also reduced the incidence of occlusions and postoperative ventricular arrhythmias, demonstrating its efficacy and safety in preventing complications after surgery without reported side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved aortocoronary bypass patency by low-dose aspirin (100 mg daily). Effects on platelet aggregation and thromboxane formation. Lorenz, RL., Schacky, CV., Weber, M., et al.[2022]

In a study of 100 patients undergoing carotid endarterectomy, a single pre-operative dose of 120 mg acetylsalicylic acid (ASA) did not significantly reduce the rate of emboli during or after the procedure.

There were no additional bleeding complications associated with ASA, indicating it is safe to use, but it did not provide the expected benefit in reducing emboli rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emboli rate during and early after carotid endarterectomy after a single preoperative dose of 120 mg acetylsalicylic acid--a prospective double-blind placebo controlled randomised trial. Tytgat, SH., Laman, DM., Rijken, AM., et al.[2016]

All six aspirin preparations tested effectively inhibited platelet aggregation to a similar extent, indicating their efficacy in reducing blood clotting, which is important for preventing heart attacks and strokes.

Ecotrin and S.R.A. showed delayed effects and inhibited platelet aggregation without measurable levels of aspirin in the bloodstream, suggesting a unique mechanism of action possibly involving acetylation of cyclooxygenase in the liver.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin kinetics and platelet aggregation in man. Siebert, DJ., Bochner, F., Imhoff, DM., et al.[2019]

A review of studies indicates that low dose aspirin (75-325 mg) does not show significant differences in safety across this range, with no increased bleeding events reported in randomized controlled trials.

Aspirin 325 mg daily may be at least as effective as 75 mg daily for preventing cardiovascular and cerebrovascular events, suggesting that higher doses could be considered based on individual patient assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The dose of aspirin for the prevention of cardiovascular and cerebrovascular events. Fisher, M., Knappertz, V.[2019]

References

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

Platelet function assessed by whole-blood aggregometry in patients undergoing non-cardiac surgery. [2013]

2. Denmark pubmed.ncbi.nlm.nih.gov

The effects of different doses of some acetylsalicylic acid formulations on platelet function and bleeding times in healthy subjects. [2019]

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

Pharmacodynamics and pharmacokinetics of a novel, low-dose, soft-gel capsule of acetylsalicylic acid in comparison with an oral solution after single-dose administration to healthy volunteers: a phase I, two-way crossover study. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Improved aortocoronary bypass patency by low-dose aspirin (100 mg daily). Effects on platelet aggregation and thromboxane formation. [2022]

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

Emboli rate during and early after carotid endarterectomy after a single preoperative dose of 120 mg acetylsalicylic acid--a prospective double-blind placebo controlled randomised trial. [2016]

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

Aspirin kinetics and platelet aggregation in man. [2019]

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

The dose of aspirin for the prevention of cardiovascular and cerebrovascular events. [2019]