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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore whether taking aspirin at specific times can help manage the blood pressure effects of celecoxib, a medication often used for pain and inflammation. Participants will try different combinations of these medications over a short period to assess how timing impacts blood pressure control. The trial seeks individuals with well-managed high blood pressure (diastolic pressure ≤100 mmHg) who do not smoke or drink heavily. As an Early Phase 1 trial, this research focuses on understanding how these treatments work together in people, offering participants a chance to contribute to groundbreaking medical insights.

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.

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

Research has shown that aspirin is usually safe for most people, with minimal impact on blood pressure or kidney function. Some individuals might experience side effects such as stomach pain, nausea, or vomiting. Serious side effects are rare but can include bleeding or black, tarry stools.

Studies have found that celecoxib, a type of pain reliever, is also generally safe. However, it can raise blood pressure, so individuals with high blood pressure should use it cautiously. Other possible side effects include stomach problems like ulcers or bleeding. Despite these risks, celecoxib is considered safe for many when used as directed.

Both aspirin and celecoxib have been used for other conditions and are well-researched, providing reassurance about their safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer potentially new approaches to blood pressure control. Celecoxib, commonly used for pain and inflammation, might also help manage blood pressure due to its anti-inflammatory properties, providing a dual benefit. Aspirin, typically known for its heart health benefits, is being explored here in a unique dosage and combination to see if it can stabilize blood pressure more effectively. Unlike standard medications that primarily focus on just lowering blood pressure, these treatments could offer additional cardiovascular benefits, making them an exciting area of investigation.

What evidence suggests that this trial's treatments could be effective for blood pressure control?

Research has shown that taking aspirin, especially at bedtime, can lower blood pressure in some people. One study found that 71% of participants experienced a drop of about 3 mm Hg in their 24-hour systolic blood pressure. In this trial, participants will receive aspirin in one phase and a placebo in another to assess its effects. Celecoxib, a pain reliever, might slightly raise blood pressure, but its overall effect is usually small. Participants in this trial will receive celecoxib in both phases to evaluate its impact. These findings suggest that while aspirin may help reduce blood pressure, celecoxib's impact is minimal. ^{6 7 8 9 10}

Who Is on the Research Team?

Carsten Skarke, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

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.

I haven't used tobacco or nicotine products for at least 3 months.

Total cholesterol of ≤270 mg/dL

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10845465/

Effect of aspirin on blood pressure in hypertensive patients This study showed no significant difference in blood pressure between the aspirin and control groups, suggesting that aspirin does not affect blood pressure.

2. revportcardiol.org revportcardiol.org/en-aspirin-blood-pressure-effects-when-articulo-S2174204917302088

Aspirin and blood pressure: Effects when used alone or in ... In conclusion, low doses of aspirin do not negatively influence BP control by antihypertensive drugs and appear to enhance cardiovascular protection when ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12386930/

Long-Term Effectiveness of Acetylsalicylic Acid in Primary ... We sought to examine the effectiveness of ASA in reducing cardiovascular diseases and overall mortality in patients at high risk by age ...

4. nature.com nature.com/articles/s41598-024-82225-w

Association between prophylactic aspirin use and ... The study results showed that the prevalence of hypertension was as high as 65.1% among the respondents who used aspirin prophylactically. The ...

5. academic.oup.com academic.oup.com/ajh/article/22/8/896/151586

Ambulatory Blood Pressure Control With Bedtime Aspirin ... A reduction of ≥3 mm Hg in the 24-h SBP mean was observed in 71% of the individuals in this group, while 6% showed increased BP after treatment. Despite the ...

6. drugs.com drugs.com/mtm/ecotrin.html

Ecotrin Uses, Side Effects & Warnings Does aspirin lower blood pressure? No, aspirin does not appear to affect blood pressure. The effects of aspirin on blood pressure have been ...

7. pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov/compound/Aspirin

Aspirin | C9H8O4 | CID 2244 - PubChem - NIH Aspirin can cause developmental toxicity and female reproductive toxicity according to an independent committee of scientific and health experts. California ...

8. cdc.gov cdc.gov/niosh/npg/npgd0010.html

Acetylsalicylic acid - NIOSH Pocket Guide to Chemical ... Symptoms: irritation eyes, skin, upper respiratory system; increased blood clotting time; nausea, vomiting; liver, kidney injury

9. ahajournals.org ahajournals.org/doi/10.1161/01.cir.101.10.1206

Aspirin | Circulation Aspirin is a relatively weak inhibitor of renal prostaglandin synthesis and does not significantly affect renal function or blood pressure control when used at ...

10. webmd.com webmd.com/drugs/2/drug-1082-3/aspirin-oral/aspirin-oral/details

Aspirin (Bayer, Vazalore, and others): Uses, Side Effects ... What are the serious side effects of aspirin? · Vomit blood · Black or tarry poop · Stomach pain that does not go away · Upset stomach · Feel faint.