Platelet Activity Assay for Blood-Thinner Monitoring in Obese Individuals

Overseen By Pavania Elavalakanar, MSc

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Beth Israel Deaconess Medical Center

Must not be taking: Antiplatelets, Anticoagulants, Antidepressants, others

Disqualifiers: Pregnancy, Cirrhosis, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

125 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test a novel diagnostic immunoassay of platelet function and compare it to the current gold standard platelet function assay by testing the response to aspirin and clopidogrel in a group of healthy volunteers and severely obese individuals and comparing the accuracy of the two tests. The secondary goals will be to evaluate the pharmacodynamic parameters of the antiplatelet agents across the two testing modalities and refine the cutoffs used for the novel assay.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications. The trial requires that you have not taken aspirin, antiplatelet drugs, NSAIDs, and other specific medications within 2 weeks before enrolling.

What data supports the effectiveness of the drug for blood-thinner monitoring in obese individuals?

Research shows that while body weight can affect how well aspirin works, using plain aspirin and ensuring patients follow their treatment can help all patients respond well. Additionally, point-of-care devices can effectively measure how aspirin and clopidogrel affect platelet function, which is important for monitoring their effectiveness. ^{1 2 3 4 5}

Is aspirin or clopidogrel generally safe for humans?

Aspirin and clopidogrel are generally safe for humans, as they have been widely used and studied for their effects on platelet function. However, some individuals may not respond well to aspirin, especially if they are heavier, but switching to a different form or adjusting the dose can help ensure effectiveness. ^{1 4 5 6 7}

How is the drug combination of aspirin and clopidogrel unique for monitoring blood-thinner effects in obese individuals?

This treatment is unique because it combines aspirin and clopidogrel to monitor platelet activity in obese individuals, who may have a poor response to aspirin alone due to their weight. The study suggests that using a specific dosage and ensuring patient compliance can improve the effectiveness of aspirin, and the combination with clopidogrel may offer a more reliable assessment of platelet function in this population. ^{1 5 8 9 10}

Eligibility Criteria

This trial is for adults over 18 who are healthy or severely obese (BMI <30 or ≥35 kg/m2), with normal kidney function, blood platelet count, and hematocrit levels. It's not for pregnant women, those with recent drug use that affects blood clotting, major illness/surgery history, gastrointestinal bleeds/ulcers, hemorrhagic stroke history, or bleeding disorders.

Inclusion Criteria

Platelet count ≥ 150 K/uL

Hematocrit ≥ 38%

Subject is willing to participate and provide informed consent

Exclusion Criteria

I am not pregnant and agree to use birth control during the study.

I have had a stomach bleed in the past 2 years or a stomach ulcer in the past year.

I have been diagnosed with cirrhosis or active cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either low or high dose aspirin or clopidogrel for 7 days to test platelet function

1 week

Daily visits for medication administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Treatment Details

Interventions

• Aspirin
• Clopidogrel

Trial Overview The study tests a new platelet activity assay against the standard test by measuring responses to aspirin and clopidogrel in volunteers. It aims to determine the accuracy of this novel assay and refine its parameters compared to traditional methods.

Participant Groups

Group I: Group E: Obese Experimental Treatment 1 Intervention

Clopidogrel 300mg on Day 1 and 75mg daily for 6 subsequent days

Group II: Group D: Obese Experimental Treatment 1 Intervention

Low Dose Aspirin - 81mg daily for 7 days

Group III: Group C: Healthy Experimental Treatment 1 Intervention

Clopidogrel 300mg on Day 1 and 75mg daily for 6 subsequent days

Group IV: Group B: Healthy Experimental Treatment 1 Intervention

High Dose Aspirin - 325mg daily for 7 days

Group V: Group A: Healthy Experimental Treatment 1 Intervention

Low Dose Aspirin - 81mg daily for 7 days

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?

Beth Israel Deaconess Medical Center

Lead Sponsor

Trials

872

Recruited

12,930,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Findings from Research

A study involving healthy volunteers compared traditional coagulation assays (bleeding time and light transmission aggregometry) with three point-of-care devices (Multiplate®, Platelet Function Analyzer-100®, and VerifyNow®) to assess platelet function after treatment with aspirin or clopidogrel.

The point-of-care devices demonstrated equal or greater effectiveness in quantifying platelet aggregation compared to traditional methods, suggesting they are reliable and easier alternatives for clinical drug development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized clinical trial comparing point-of-care platelet function assays and bleeding time in healthy subjects treated with aspirin or clopidogrel. Chen, F., Maridakis, V., O'neill, EA., et al.[2018]

In a study of 316 patients on dual antiplatelet therapy after angioplasty, class 1 obesity was linked to increased platelet activation markers, indicating a heightened response to arachidonic acid.

Despite the increased platelet activation in obese patients, there was no significant difference in thromboxane generation or platelet reactivity between patients weighing ≥70 kg and those below this weight, suggesting that obesity does not affect the efficacy of aspirin in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Residual platelet reactivity in low-dose aspirin-treated patients with class 1 obesity. Lee, S., Eichelberger, B., Kopp, CW., et al.[2021]

Aspirin effectively inhibits platelet aggregation in healthy adults without diabetes, regardless of body weight or body mass index (BMI), based on studies involving 150 participants across two cohorts.

The study suggests that the reduced effectiveness of low-dose aspirin in preventing cardiovascular events in heavier individuals may be due to mechanisms other than platelet aggregation, as no correlation was found between BMI and aspirin's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platelet inhibition by low-dose aspirin is not influenced by body mass or weight. Heffron, SP., Windheim, J., Barrett, TJ., et al.[2023]

In a study involving 20 patients on dual antiplatelet therapy, light transmission aggregometry (LTA) and VerifyNow showed the highest agreement for monitoring P2Y12 inhibitors, with 75% agreement and strong correlation coefficients, indicating they are reliable methods for assessing antiplatelet effects.

The overall agreement between different testing platforms for aspirin response was lower, ranging from 35% to 60%, suggesting that LTA remains the preferred method for monitoring dual antiplatelet therapy, while VerifyNow is a suitable alternative for P2Y12 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Sticky Situation: Variable Agreement Between Platelet Function Tests Used to Assess Anti-platelet Therapy Response. Nakahara, H., Sarker, T., Dean, CL., et al.[2022]

In a study of 138 cardiology patients, 25% initially showed inadequate response to aspirin, but after ensuring compliance, only 5% were considered non-responders, highlighting the importance of patient adherence in treatment outcomes.

Heavier patients (over 90 kg or with a BMI over 32) were more likely to be non-responders to aspirin, suggesting that a tailored approach using plain aspirin for these individuals could improve response rates without the need for extensive testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight as an assay-independent predictor of poor response to enteric aspirin in cardiovascular patients. McCall, M., Peace, A., Tedesco, AF., et al.[2020]

In a study involving clopidogrel-naive patients undergoing elective PCI, the VASP-assay and VerifyNow P2Y12-assay were found to strongly correlate with the peak plasma levels of the active metabolite of clopidogrel, indicating their effectiveness in monitoring clopidogrel responsiveness.

The study suggests that the VASP-assay and VerifyNow assays are preferable for assessing platelet function related to clopidogrel, while other tests like the IMPACT-R ADP test showed no correlation with the active metabolite levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Which platelet function test is suitable to monitor clopidogrel responsiveness? A pharmacokinetic analysis on the active metabolite of clopidogrel. Bouman, HJ., Parlak, E., van Werkum, JW., et al.[2023]

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]

In a study of 51 patients with arterial hypertension and abdominal obesity, verospiron significantly improved platelet aggregation and reduced lipid peroxidation over 16 weeks, while hypothiazide showed no effect on these parameters.

The findings suggest that combining verospiron with non-medication therapies may be beneficial for weight reduction in these patients, highlighting its potential as a therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The use of verospiron and the degree of platelet aggregation in arterial hypertension with abdominal obesity]. Medvedev, IN., Briukhovetskiĭ, AG.[2014]

The novel ROTEM platelet assay demonstrated high specificity in differentiating between patients on aspirin therapy and healthy individuals, with an impressive ROC AUC of 0.99, indicating its potential for clinical use.

While ROTEM-PTL showed moderate correlation with established assays like MEA and LTA, further clinical trials are necessary to assess its effectiveness in identifying patients at risk for adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platelet Reactivity in Patients on Aspirin and Clopidogrel Therapy Measured by a New Bedside Whole-Blood Assay. Polzin, A., Helten, C., Dannenberg, L., et al.[2020]

The study involved 154 patients with cardiovascular disease and assessed the effects of aspirin and clopidogrel on platelet function using two different analyzers: PFA-100 and Multiplate.

The PFA-100 was effective in detecting the effects of aspirin on platelet function but failed to detect clopidogrel's effects, whereas the Multiplate analyzer successfully identified the effects of both medications, making it a more comprehensive tool for evaluating antiplatelet therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility of the PFA-100 instrument and the novel multiplate analyzer for the assessment of aspirin and clopidogrel effects on platelet function in patients with cardiovascular disease. Mueller, T., Dieplinger, B., Poelz, W., et al.[2019]

References

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

A randomized clinical trial comparing point-of-care platelet function assays and bleeding time in healthy subjects treated with aspirin or clopidogrel. [2018]

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

Residual platelet reactivity in low-dose aspirin-treated patients with class 1 obesity. [2021]

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

Platelet inhibition by low-dose aspirin is not influenced by body mass or weight. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

A Sticky Situation: Variable Agreement Between Platelet Function Tests Used to Assess Anti-platelet Therapy Response. [2022]

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

Weight as an assay-independent predictor of poor response to enteric aspirin in cardiovascular patients. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Which platelet function test is suitable to monitor clopidogrel responsiveness? A pharmacokinetic analysis on the active metabolite of clopidogrel. [2023]

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

Aspirin kinetics and platelet aggregation in man. [2019]

8. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[The use of verospiron and the degree of platelet aggregation in arterial hypertension with abdominal obesity]. [2014]

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

Platelet Reactivity in Patients on Aspirin and Clopidogrel Therapy Measured by a New Bedside Whole-Blood Assay. [2020]

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

Utility of the PFA-100 instrument and the novel multiplate analyzer for the assessment of aspirin and clopidogrel effects on platelet function in patients with cardiovascular disease. [2019]