Myocardial InfarctionNCT00646906
Mechanisms of Action of Acetaminophen
A study testing Aspirin First, Aspirin Last and Acetaminophen 1000 mg/d in people with Myocardial Infarction and Arthritis, run by University of Pennsylvania at 1 site in United States.
Trial summary
This research study investigates whether the ability of aspirin to reduce the risk of heart attacks may be diminished by the administration of acetaminophen. Patients who have heart disease are often prescribed aspirin because of its unique ability to permanently prevent platelets from aggregating and forming a blood… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Myocardial Infarction, Arthritis
- What is being tested?
- Aspirin First, Aspirin Last and Acetaminophen 1000 mg/d
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Jun 2004to 24 Jan 2012
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age between 18 - 55
- Subjects recruited for the "non-smoker group" must be in good health as based on medical history, physical examination, vital signs, and laboratory tests.
- Subjects recruited for the "smokers group" will be chronic smokers of at least 4 years duration, but no longer than 20 years duration, who smoke 11-20 cigarettes per day. Smokers must be otherwise healthy as described above.
- Female subjects of child bearing potential must be using a medically acceptable method of contraception (oral contraception, depo-provera injection, intrauterine device, condom with spermicide, diaphragm, cervical cap, progestin implant, abstinence, tubal ligation, oophorectomy, TAH) throughout the entire study period. All female subjects must consent to a urine pregnancy test at screening and just prior to the start of each treatment phase of the study, which must be negative at all time points.
- Subjects must be within 30% of their ideal body weight.
Who cannot join
- Female subjects who are pregnant or nursing a child.
- Subjects, who have received an experimental drug, used an experimental medical device within 30 days prior to screening, or who gave a blood donation of ≥ one pint within 8 weeks prior to screening.
- Subjects with any coagulation, bleeding or blood disorders.
- Subjects who are sensitive or allergic to acetaminophen and/or aspirin, as well as any of their components.
- Subjects with documented history of any gastrointestinal disorders, including bleeding ulcers.
- Subjects with any evidence of cancer.
Show all 13Show fewer
- Subjects with a history of heart disease, including myocardial infarction, angina, coronary artery disease, any evidence of coronary artery stenosis, arrhythmias, heart failure, having had a coronary intervention or significant irregularities in the EKG.
- Subjects with history of peripheral artery disease (claudication, bypass surgery or stent placement in extremity.)
- Subjects with a history of stroke or transitory ischemic attacks.
- Subjects with renal, hepatic, respiratory, endocrine, metabolic, hematopoietic or neurological disorder.
- Subjects with a history of liver disease or abnormal liver function tests (>2x upper limit normal).
- Subjects with any abnormal laboratory value or physical finding that according to the investigator may interfere with interpretation of the study results, be indicative of an underlying disease state, or compromise the safety of a potential subject.
- Subjects who have had a history of drug or alcohol abuse within the last 6 months.
Trial locations and contacts
1 site in 1 country.
United States1 site
Hospital of The University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Randomized, Double-Blind, Crossover Study to Evaluate the Mechanism of Action of Acetaminophen
This research study investigates whether the ability of aspirin to reduce the risk of heart attacks may be diminished by the administration of acetaminophen. Patients who have heart disease are often prescribed aspirin because of its unique ability to permanently prevent platelets from aggregating and forming a blood clot. Such blood clots cause heart attacks when they form in a blood vessel that supplies the heart with oxygen rich blood. Some of these same patients also take acetaminophen everyday for relief from arthritis pain. Higher doses of acetaminophen may also have the ability to prevent the platelets from clotting, however only temporarily. Therefore, this study evaluates whether the timing of the administration of acetaminophen (before or after aspirin) interferes with the permanent blood clotting effects of aspirin.
The primary hypothesis is that acetaminophen given two hours before aspirin will antagonize the effects of aspirin, while reversing the order of administration will not.
Read the detailed description
Acetaminophen has antipyretic and moderate analgesic properties, but largely lacks anti-inflammatory activity. While its mechanism of action is not entirely understood, it is probably both an isoform nonspecific and partial cyclooxygenase (COX) inhibitor in humans at doses commonly taken for mild pain and pyrexia, such as 1000 mg. Although no inhibition of platelet aggregation is observed at this dosage, platelet thromboxane formation by COX is depressed by roughly 40%. Epidemiological studies suggest that at higher doses, 2000 mg and above, acetaminophen exhibits a gastrointestinal adverse effect profile indistinguishable from traditional, nonspecific NSAIDs. Thus, it is possible that maximal COX inhibition is achieved at higher doses. Interestingly, complete COX inhibition by non-selective COX inhibitors has the potential to antagonize the irreversible platelet inhibition induced by aspirin. In contrast to reversible inhibitors, aspirin acts by acetylation of a serine residue in the substrate binding channel of COX. For example, ibuprofen, a reversible and non-selective COX inhibitor, is thought to prevent aspirin from gaining access to this target site. This study investigates, whether COX inhibition by acetaminophen is dose dependent in humans and whether acetaminophen interacts with the irreversible COX inhibition by low dose aspirin. It addresses the dose-related effect of acetaminophen on COX activity and assesses potential pharmacological interactions with low dose aspirin in normal healthy volunteers. The primary hypothesis is that administrating acetaminophen before aspirin would antagonize the irreversible effects of aspirin, as assessed by the measurement of serum thromboxane B2 24 hrs after the administration of the first study drug on day 6 of combination therapy.
The second aim will determine the effects of acetaminophen on oxidant stress and cyclooxygenase activity in patients who smoke. While the structural interaction of acetaminophen with COX is unknown, it may inactivate the enzyme by a molecular mechanism different from other NSAIDs. Thus, acetaminophen, which is a good reducing agent, might act to reduce COX from its active, oxidized form. When uninhibited, the peroxidase component of this bifunctional enzyme oxidizes its catalytic center to generate a tyrosyl radical that is required for its activity. Indeed, some reducing agents have the capacity to prevent COX activation in vitro. If reduction were the basis for COX inhibition by acetaminophen in vivo, it would be expected to be less pronounced under conditions of high peroxide tone, as occurs in inflammation. Indeed, acetaminophen, which is a phenol derivative, may act as a free radical scavenging antioxidant like other phenolic compounds, such as vitamin E and has been shown to alleviate oxidative damage in model systems. This study explores the potential antioxidant effect of acetaminophen in smokers. Such individuals represent a human model of oxidant stress. Novel approaches to the quantitative assessment of free radical induced damage to lipids are applied, which are elevated in smokers. Additionally, it is determined whether COX inhibition by acetaminophen is conditioned by oxidant tone in vivo.
The third aim, will compare the degree of COX inhibition by acetaminophen with that of a thoroughly characterized nonselective COX inhibitor, ibuprofen.
- Conditions
- Myocardial Infarction, Arthritis
- Being tested
- Aspirin First, Aspirin Last, Acetaminophen 1000 mg/d, Acetaminophen 4000 mg/d, Ibuprofen 800 mg/d
- Keywords
- acetaminophen, low dose aspirin, cyclooxygenase, prostaglandin, drug interaction, platelet inhibition, urinary prostaglandin metabolites, oxidant stress, smoking
- Medical subject headings
- Myocardial Infarction, Arthritis, Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aspirin FirstDrug
Crossover period Aspirin First: Subjects will receive 81 mg aspirin at approximately 8 am followed by acetaminophen at approximately 10 am.
Aspirin LastDrug
Crossover period Aspirin Last: Subjects will receive acetaminophen at approximately 8 am followed by 81 mg aspirin at approximately 10 am.
Acetaminophen 1000 mg/dDrug
Subjects will receive a daily oral dose of 1000 mg acetaminophen for six days each administered at 8 AM.
Acetaminophen 4000 mg/dDrug
Crossover period Acetaminophen 4000 mg/d: Acetaminophen (1000 mg p.o.) orally at 8 AM, 2 PM, 8 PM and 2 AM for 3 days. The last dose will be administered on day four at 8 AM.
Ibuprofen 800 mg/dDrug
Crossover period Ibuprofen 800 mg/d: Ibuprofen (200 mg) orally at at 8 AM, 2 PM, 8 PM and 2 AM for 3 days. The last dose will be administered on day four at 8 AM.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1a: Acetaminophen 1000mg / aspirin | Experimental | All subjects in this arm (smokers (n=8) and non-smokers (n=8) will receive 81 mg aspirin at approximately 8 am followed by 1000 mg acetaminophen at approximately 10 am during one crossover period (see "Crossover period: Aspirin first" intervention). During the other crossover period, beginning after a 2 week washout, the order will be reversed and the subjects will receive 1000 mg acetaminophen at 8 am followed by 81 mg aspirin at 10 am (see "Crossover Period: Aspirin last" intervention). The occurrence of the two crossover periods will be randomized by order. Smokers and non-smokers will be matched for age and gender. Receives: Drug: Aspirin First; Drug: Aspirin Last |
| Phase 1a: Acetaminophen 2000mg / aspirin | Experimental | All subjects in this arm (smokers (n=8) and non-smoking volunteers (n=8)) will receive 81 mg aspirin at approximately 8 am followed by 2000 mg acetaminophen at approximately 10 am during one crossover period (see "Crossover Period: Aspirin first" intervention). During the other crossover period, beginning after a 2 week washout, the order will be reversed and the subjects will receive 2000 mg acetaminophen at 8 am followed by 81 mg aspirin at 10 am (see "Crossover Period: Aspirin last" intervention). The occurrence of the two crossover periods will be randomized by order. Smokers and non-smokers will be matched for age and gender. Receives: Drug: Aspirin First; Drug: Aspirin Last |
| Phase 1b: Acetaminophen 1000 mg alone | Experimental | Eight male and non-pregnant female subjects who are healthy and non-smoking will be recruited. They will receive a daily oral dose of 1000 mg acetaminophen for six days each administered at 8 AM (see "Acetaminophen 1000 mg/d" intervention). Study assessments will be performed on day 1 and on day 6. This is not a crossover design. Just one treatment period. Receives: Drug: Acetaminophen 1000 mg/d |
| Phase 2: Acetaminophen vs. Ibuprofen | Experimental | Eight male and non-pregnant female subjects who are healthy and non-smoking will be recruited. In one period of this crossover study acetaminophen (1000 mg p.o.) will be administered orally at 8 AM, 2 PM, 8 PM and 2 AM for 3 days (see "Crossover Period: Acetaminophen 4000 mg/d" intervention). The last dose will be administered on day four at 8 AM In the other crossover period, after a washout period of at least 14 days, the subjects will receive ibuprofen (200 mg) orally at at 8 AM, 2 PM, 8 PM and 2 AM for 3 days (see "Crossover Period: Ibuprofen 800 mg/d" intervention). The last dose will be administered on day four at 8 AM Study assessments will be performed on day 1 and day 4 of each crossover period. The occurrence of the two crossover periods will be randomized by order. Receives: Drug: Acetaminophen 4000 mg/d; Drug: Ibuprofen 800 mg/d |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Serum Thromboxane B2
Thromboxan B2 is a stable metabolite of thromboxane A2. Thromboxane B2 formation during clotting of whole blood (37 degrees Celsius, 1 hour) is reflective of the capacity of platelets to form thromboxane A2. Serum Thromboxane B2 was measured by radio-immuno assay. The quantity of interest was percent change from start (8:00 am on day 1) to finish (8:00 am on last day) of each crossover period in serum thromboxane B2. This was calculated as: 100%*(value at start of period minus value at end of period)/value at start of period.
Measured: 7 days (Phase 1a and 1b), 4 days (Phase 2)
Secondary outcomes (1)
Percent Change in Arachidonic Acid Induced Platelet Aggregation
Platelet aggregation was induced by 500 micro molar arachidonic acid using a Chronolog aggregometer. The quantity of interest was percent change from start (8:00 am on day 1) to finish (8:00 am on last day) of each crossover period in platelet aggregation. This was calculated as: 100%*(value at start of period minus value at end of period)/value at start of period.
Measured: 7 days (only Phase 1a)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2008 (estimated)
- Study start2 Jun 2004
- Primary completion24 Jan 2012
- Study completion24 Jan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Myocardial InfarctionStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Garret A. FitzGerald, MD, Principal investigator, University of Pennsylvania, Institute for Translationals Medicine and TherapeuticsSusanne Fries, MD, Principal investigator, University of Pennsylvania, Institute for Translationals Medicine and TherapeuticsTilo Grosser, MD, Principal investigator, University of Pennsylvania, Institute for Translationals Medicine and Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00646906
- Sponsor's protocol ID
- 708270
- Status last verified
- Jan 2026
- First submitted
- 26 Mar 2008
- Last updated
- 12 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Crossover Study to Evaluate the Mechanism of Action of Acetaminophen
- ClinicalTrials.gov ID
- NCT00646906
- Acronym / sponsor ID
- 708270
- Conditions
- Myocardial Infarction, Arthritis
- Keywords
- acetaminophen, low dose aspirin, cyclooxygenase, prostaglandin, drug interaction, platelet inhibition, urinary prostaglandin metabolites, oxidant stress
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 2 Jun 2004 (actual)
- Primary completion
- 24 Jan 2012 (actual)
- Study completion
- 24 Jan 2012 (actual)
- First posted
- 31 Mar 2008 (estimated)
- Results
- Posted 3 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study investigates whether the ability of aspirin to reduce the risk of heart attacks may be diminished by the administration of acetaminophen. Patients who have heart disease are often prescribed aspirin because of its unique ability to permanently prevent platelets from aggregating and forming a blood clot. Such blood clots cause heart attacks when they form in a blood vessel that supplies the heart with oxygen rich blood. Some of these same patients also take acetaminophen everyday for relief from arthritis pain. Higher doses of acetaminophen may also have the ability to prevent the platelets from clotting, however only temporarily. Therefore, this study evaluates whether the timing of the administration of acetaminophen (before or after aspirin) interferes with the permanent blood clotting effects of aspirin.
The primary hypothesis is that acetaminophen given two hours before aspirin will antagonize the effects of aspirin, while reversing the order of administration will not.
Detailed description
Acetaminophen has antipyretic and moderate analgesic properties, but largely lacks anti-inflammatory activity. While its mechanism of action is not entirely understood, it is probably both an isoform nonspecific and partial cyclooxygenase (COX) inhibitor in humans at doses commonly taken for mild pain and pyrexia, such as 1000 mg. Although no inhibition of platelet aggregation is observed at this dosage, platelet thromboxane formation by COX is depressed by roughly 40%. Epidemiological studies suggest that at higher doses, 2000 mg and above, acetaminophen exhibits a gastrointestinal adverse effect profile indistinguishable from traditional, nonspecific NSAIDs. Thus, it is possible that maximal COX inhibition is achieved at higher doses. Interestingly, complete COX inhibition by non-selective COX inhibitors has the potential to antagonize the irreversible platelet inhibition induced by aspirin. In contrast to reversible inhibitors, aspirin acts by acetylation of a serine residue in the substrate binding channel of COX. For example, ibuprofen, a reversible and non-selective COX inhibitor, is thought to prevent aspirin from gaining access to this target site. This study investigates, whether COX inhibition by acetaminophen is dose dependent in humans and whether acetaminophen interacts with the irreversible COX inhibition by low dose aspirin. It addresses the dose-related effect of acetaminophen on COX activity and assesses potential pharmacological interactions with low dose aspirin in normal healthy volunteers. The primary hypothesis is that administrating acetaminophen before aspirin would antagonize the irreversible effects of aspirin, as assessed by the measurement of serum thromboxane B2 24 hrs after the administration of the first study drug on day 6 of combination therapy.
The second aim will determine the effects of acetaminophen on oxidant stress and cyclooxygenase activity in patients who smoke. While the structural interaction of acetaminophen with COX is unknown, it may inactivate the enzyme by a molecular mechanism different from other NSAIDs. Thus, acetaminophen, which is a good reducing agent, might act to reduce COX from its active, oxidized form. When uninhibited, the peroxidase component of this bifunctional enzyme oxidizes its catalytic center to generate a tyrosyl radical that is required for its activity. Indeed, some reducing agents have the capacity to prevent COX activation in vitro. If reduction were the basis for COX inhibition by acetaminophen in vivo, it would be expected to be less pronounced under conditions of high peroxide tone, as occurs in inflammation. Indeed, acetaminophen, which is a phenol derivative, may act as a free radical scavenging antioxidant like other phenolic compounds, such as vitamin E and has been shown to alleviate oxidative damage in model systems. This study explores the potential antioxidant effect of acetaminophen in smokers. Such individuals represent a human model of oxidant stress. Novel approaches to the quantitative assessment of free radical induced damage to lipids are applied, which are elevated in smokers. Additionally, it is determined whether COX inhibition by acetaminophen is conditioned by oxidant tone in vivo.
The third aim, will compare the degree of COX inhibition by acetaminophen with that of a thoroughly characterized nonselective COX inhibitor, ibuprofen.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Phase 1a: Acetaminophen 1000mg / aspirin | Experimental | Drug: Aspirin First, Drug: Aspirin LastAll subjects in this arm (smokers (n=8) and non-smokers (n=8) will receive 81 mg aspirin at approximately 8 am followed by 1000 mg acetaminophen at approximately 10 am during one crossover period (see "Crossover period: Aspirin first" intervention). During the other crossover period, beginning after a 2 week washout, the order will be reversed and the subjects will receive 1000 mg acetaminophen at 8 am followed by 81 mg aspirin at 10 am (see "Crossover Period: Aspirin last" intervention). The occurrence of the two crossover periods will be randomized by order. Smokers and non-smokers will be matched for age and gender. |
| Phase 1a: Acetaminophen 2000mg / aspirin | Experimental | Drug: Aspirin First, Drug: Aspirin LastAll subjects in this arm (smokers (n=8) and non-smoking volunteers (n=8)) will receive 81 mg aspirin at approximately 8 am followed by 2000 mg acetaminophen at approximately 10 am during one crossover period (see "Crossover Period: Aspirin first" intervention). During the other crossover period, beginning after a 2 week washout, the order will be reversed and the subjects will receive 2000 mg acetaminophen at 8 am followed by 81 mg aspirin at 10 am (see "Crossover Period: Aspirin last" intervention). The occurrence of the two crossover periods will be randomized by order. Smokers and non-smokers will be matched for age and gender. |
| Phase 1b: Acetaminophen 1000 mg alone | Experimental | Drug: Acetaminophen 1000 mg/dEight male and non-pregnant female subjects who are healthy and non-smoking will be recruited. They will receive a daily oral dose of 1000 mg acetaminophen for six days each administered at 8 AM (see "Acetaminophen 1000 mg/d" intervention). Study assessments will be performed on day 1 and on day 6. This is not a crossover design. Just one treatment period. |
| Phase 2: Acetaminophen vs. Ibuprofen | Experimental | Drug: Acetaminophen 4000 mg/d, Drug: Ibuprofen 800 mg/dEight male and non-pregnant female subjects who are healthy and non-smoking will be recruited. In one period of this crossover study acetaminophen (1000 mg p.o.) will be administered orally at 8 AM, 2 PM, 8 PM and 2 AM for 3 days (see "Crossover Period: Acetaminophen 4000 mg/d" intervention). The last dose will be administered on day four at 8 AM In the other crossover period, after a washout period of at least 14 days, the subjects will receive ibuprofen (200 mg) orally at at 8 AM, 2 PM, 8 PM and 2 AM for 3 days (see "Crossover Period: Ibuprofen 800 mg/d" intervention). The last dose will be administered on day four at 8 AM Study assessments will be performed on day 1 and day 4 of each crossover period. The occurrence of the two crossover periods will be randomized by order. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Age between 18 - 55
- Subjects recruited for the "non-smoker group" must be in good health as based on medical history, physical examination, vital signs, and laboratory tests.
- Subjects recruited for the "smokers group" will be chronic smokers of at least 4 years duration, but no longer than 20 years duration, who smoke 11-20 cigarettes per day. Smokers must be otherwise healthy as described above.
- Female subjects of child bearing potential must be using a medically acceptable method of contraception (oral contraception, depo-provera injection, intrauterine device, condom with spermicide, diaphragm, cervical cap, progestin implant, abstinence, tubal ligation, oophorectomy, TAH) throughout the entire study period. All female subjects must consent to a urine pregnancy test at screening and just prior to the start of each treatment phase of the study, which must be negative at all time points.
- Subjects must be within 30% of their ideal body weight.
Key exclusion criteria (13 listed)
- Female subjects who are pregnant or nursing a child.
- Subjects, who have received an experimental drug, used an experimental medical device within 30 days prior to screening, or who gave a blood donation of ≥ one pint within 8 weeks prior to screening.
- Subjects with any coagulation, bleeding or blood disorders.
- Subjects who are sensitive or allergic to acetaminophen and/or aspirin, as well as any of their components.
- Subjects with documented history of any gastrointestinal disorders, including bleeding ulcers.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aspirin FirstCrossover period Aspirin First: Subjects will receive 81 mg aspirin at approximately 8 am followed by acetaminophen at approximately 10 am. | Drug | Phase 1a: Acetaminophen 1000mg / aspirin, Phase 1a: Acetaminophen 2000mg / aspirin |
| Aspirin LastCrossover period Aspirin Last: Subjects will receive acetaminophen at approximately 8 am followed by 81 mg aspirin at approximately 10 am. | Drug | Phase 1a: Acetaminophen 1000mg / aspirin, Phase 1a: Acetaminophen 2000mg / aspirin |
| Acetaminophen 1000 mg/dSubjects will receive a daily oral dose of 1000 mg acetaminophen for six days each administered at 8 AM. | Drug | Phase 1b: Acetaminophen 1000 mg alone |
| Acetaminophen 4000 mg/dCrossover period Acetaminophen 4000 mg/d: Acetaminophen (1000 mg p.o.) orally at 8 AM, 2 PM, 8 PM and 2 AM for 3 days. The last dose will be administered on day four at 8 AM. | Drug | Phase 2: Acetaminophen vs. Ibuprofen |
| Ibuprofen 800 mg/dCrossover period Ibuprofen 800 mg/d: Ibuprofen (200 mg) orally at at 8 AM, 2 PM, 8 PM and 2 AM for 3 days. The last dose will be administered on day four at 8 AM. | Drug | Phase 2: Acetaminophen vs. Ibuprofen |
Primary outcome
Percent Change in Serum Thromboxane B2
Time frame: 7 days (Phase 1a and 1b), 4 days (Phase 2)
Thromboxan B2 is a stable metabolite of thromboxane A2. Thromboxane B2 formation during clotting of whole blood (37 degrees Celsius, 1 hour) is reflective of the capacity of platelets to form thromboxane A2. Serum Thromboxane B2 was measured by radio-immuno assay. The quantity of interest was percent change from start (8:00 am on day 1) to finish (8:00 am on last day) of each crossover period in serum thromboxane B2. This was calculated as: 100%*(value at start of period minus value at end of period)/value at start of period.
1 secondary outcome
Percent Change in Arachidonic Acid Induced Platelet Aggregation
Time frame: 7 days (only Phase 1a)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Institute for Translational Medicine and Therapeutics, University of PennsylvaniaLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Garret A. FitzGerald, MD principal investigator
University of Pennsylvania, Institute for Translationals Medicine and Therapeutics
Susanne Fries, MD principal investigator
University of Pennsylvania, Institute for Translationals Medicine and Therapeutics
Tilo Grosser, MD principal investigator
University of Pennsylvania, Institute for Translationals Medicine and Therapeutics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Aspirin First, Aspirin Last and Acetaminophen 1000 mg/d in people with Myocardial Infarction and Arthritis, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in Serum Thromboxane B2 (time frame: 7 days (Phase 1a and 1b), 4 days (Phase 2)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2026.