Aspirin + Celecoxib for Blood Pressure Control

Overseen By LaVenia Banas, CRN

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Pennsylvania

Must not be taking: NSAIDs, Antisecretory agents, Antiplatelets, Anticoagulants

Disqualifiers: Pregnancy, Cardiovascular disease, Cancer, others

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

Compensation: Varies

Number of Visits: 2

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as NSAIDs (like aspirin or ibuprofen), proton pump inhibitors, H2 blockers, and certain anti-platelet or anti-coagulant agents, at least 2 weeks before starting the study. If you are on other chronic medications, you may be considered for inclusion on a case-by-case basis.

What data supports the effectiveness of the drug Aspirin + Celecoxib for blood pressure control?

Aspirin is known for its ability to prevent blood clots, which can help reduce the risk of heart attacks and strokes. This is due to its effect on platelets, which are small blood cells that help with clotting. While this doesn't directly address blood pressure control, it shows aspirin's role in cardiovascular health. ^{1 2 3 4 5}

Is the combination of aspirin and celecoxib generally safe for humans?

Aspirin can increase bleeding risk, especially at higher doses, while celecoxib may cause gastrointestinal, cardiovascular, and kidney issues. Both drugs have been used safely for various conditions, but they can have serious side effects, so it's important to consult a doctor before use. ^{2 6 7 8 9}

How does the drug Aspirin + Celecoxib for blood pressure control differ from other treatments?

The combination of Aspirin and Celecoxib for blood pressure control is unique because it combines an antiplatelet agent (Aspirin) with a nonsteroidal anti-inflammatory drug (Celecoxib), which may offer a novel approach to managing blood pressure by addressing both inflammation and platelet aggregation, unlike standard antihypertensive drugs that primarily target blood pressure alone. ^{2 10 11 12 13}

What is the purpose of this trial?

To determine whether timed administration of aspirin ameliorates the effects of celecoxib on blood pressure.

Research Team

Carsten Skarke, MD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for healthy adults over 18 who don't smoke, drink moderately, and have a BMI between 18-30. Women must use contraception and not be pregnant or nursing. Participants can't have bleeding disorders, allergies to aspirin or celecoxib, recent drug trials participation, significant health issues, or take certain medications.

Inclusion Criteria

I am over 18 years old.

Total cholesterol of ≤270 mg/dL

Body mass index (BMI) between 18 and 30 kg/m2

Exclusion Criteria

I have not taken NSAIDs or stomach acid reducers in the last 2 weeks.

You have had problems with drugs or alcohol in the past 6 months.

Volunteers enrolled in the sub-study who do not own a smartphone

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Participants receive either aspirin or placebo, and celecoxib for 7 days

7 days

1 visit (in-person)

Phase 2 Treatment

Participants receive the alternate treatment (aspirin or placebo) and celecoxib for another 7 days

7 days

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

Treatment Details

Interventions

• Aspirin
• Celecoxib

Trial Overview The study tests if taking aspirin at specific times lessens the impact of celecoxib on blood pressure in healthy individuals. It involves administering low-dose aspirin with celecoxib capsules under controlled conditions to monitor their effects.

Participant Groups

Group I: Celecoxib 200mg capsule Experimental Treatment 2 Interventions

Participants will receive celecoxib in Phase 1 and Phase 2 over 7 days. This is open, meaning participant and investigator will recognize celecoxib capsules.

Group II: Aspirin 81 mg/Placebo Experimental Treatment 2 Interventions

Participants will receive aspirin in Phase 1 followed by matched placebo in Phase 2, or vice versa, over 14 days. The order will be randomized and aspirin/placebo will be double-blinded.

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 Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Findings from Research

In a study of 189 subjects, only those who underwent surgical extraction while taking 81 mg of aspirin (ASA) showed bleeding after 24 hours, indicating a potential risk associated with surgical procedures.

However, the study concluded that patients taking daily aspirin could safely undergo simple dental extractions without significant bleeding risks, as no bleeding was observed in the other groups after 48 hours and 5 days post-operation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of aspirin on bleeding after extraction of teeth. Nooh, N.[2022]

Aspirin, celebrating its 100-year anniversary, is now recognized for its crucial role in treating cardiovascular and cerebrovascular diseases by irreversibly inhibiting thromboxane A2, which helps prevent blood clots.

While aspirin effectively reduces risks in patients with existing heart and brain conditions, its use for primary prevention is controversial due to a lack of overall mortality reduction and potential serious side effects, such as increased bleeding, especially at higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Acetylsalicylic acid in the treatment of cardiovascular and cerebrovascular diseases]. Landmark, K.[2013]

Ascolong, a new buccal form of aspirin with a very low dose of 12.5 mg, demonstrated a reliable antiaggregant effect in both single and regular doses, although it was less pronounced than that of standard 100 mg aspirin tablets.

The study, involving 43 healthy men and 19 patients with coronary or cerebrovascular disorders, found that Ascolong was well tolerated and effectively delivered acetylsalicylic acid (ASA) into the bloodstream, reducing its metabolism into a less active form, making it a promising option for patients who cannot take traditional oral aspirin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ascolong: a new buccal dosage form of acetylsalicylic acid to be used and antiaggregant]. Kokurina, EV., Suslina, ZA., Khromov, GL., et al.[2013]

Rofecoxib, a selective COX-2 inhibitor, was associated with a significantly higher rate of hospitalizations due to acute hypertension compared to celecoxib, with a 3.8-fold increase in reporting rates during the first three years of marketing.

The findings align with previous clinical trial data, indicating that rofecoxib may pose a greater risk for hypertension, particularly in older patients who are already at higher risk for cardiovascular issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spontaneous reports of hypertension leading to hospitalisation in association with rofecoxib, celecoxib, nabumetone and oxaprozin. Brinker, A., Goldkind, L., Bonnel, R., et al.[2018]

Celecoxib is associated with a slightly increased risk of certain adverse events, such as edema, hypertension, angioedema, and allergic reactions compared to placebo, but these risks are relatively small.

In contrast, celecoxib shows a lower risk of gastrointestinal issues like hemorrhage and ulceration compared to non-selective NSAIDs, suggesting it may be a safer option for patients concerned about GI side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of celecoxib compared with placebo and non-selective NSAIDs: cumulative meta-analysis of 89 randomized controlled trials. Essex, MN., Zhang, RY., Berger, MF., et al.[2022]

A comprehensive list of acetylsalicylic acid (ASA) and nonsteroidal anti-inflammatory drugs (NSAIDs) has been compiled to highlight the risk of serious side effects and drug interactions, especially in patients on anticoagulant therapy.

Physicians should be vigilant in preventing patients from inadvertently taking multiple ASA or NSAID products, and patients are advised to consult their doctor before starting any new medication, including over-the-counter options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acetylsalicylic-acid-containing drugs and nonsteroidal anti-inflammatory drugs available in Canada. Brigden, M., Smith, RE.[2013]

References

1. Saudi Arabia pubmed.ncbi.nlm.nih.gov

The effect of aspirin on bleeding after extraction of teeth. [2022]

2. Norway pubmed.ncbi.nlm.nih.gov

[Acetylsalicylic acid in the treatment of cardiovascular and cerebrovascular diseases]. [2013]

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

Low-dose aspirin therapy is not a reason for repeating head computed tomographic scans in traumatic brain injury: a prospective study. [2016]

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

[Ascolong: a new buccal dosage form of acetylsalicylic acid to be used and antiaggregant]. [2013]

5. Poland pubmed.ncbi.nlm.nih.gov

[Aspirin resistance theory]. [2015]

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

Spontaneous reports of hypertension leading to hospitalisation in association with rofecoxib, celecoxib, nabumetone and oxaprozin. [2018]

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

Safety of celecoxib compared with placebo and non-selective NSAIDs: cumulative meta-analysis of 89 randomized controlled trials. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Potentially inappropriate concomitant medicine use with the selective COX-2 inhibitor celecoxib: Analysis and comparison of spontaneous adverse event reports from Australia, Canada and the USA. [2019]

9. Canada pubmed.ncbi.nlm.nih.gov

Acetylsalicylic-acid-containing drugs and nonsteroidal anti-inflammatory drugs available in Canada. [2013]

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

Effects of low-dose aspirin on clinic and ambulatory blood pressure in treated hypertensive patients. Collaborative Group of the Primary Prevention Project (PPP)--Hypertension study. [2022]

11. China pubmed.ncbi.nlm.nih.gov

[Effect of low-dosage aspirin combined with perindopril on prostacyclin, thromboxone A2, and norepinephrine in rabbits' blood]. [2013]

12. Germany pubmed.ncbi.nlm.nih.gov

High on treatment platelet reactivity against aspirin by non-steroidal anti-inflammatory drugs--pharmacological mechanisms and clinical relevance. [2013]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Low-dose aspirin does not interfere with the blood pressure-lowering effects of antihypertensive therapy. [2019]