Mechanism Based Resistance to Aspirin

NCT00948987 | Completed Phase 1 DMC

• 2 other identifiers: 8019070926
• Study Type: interventional
• Target: 400
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this research is to study why some people do not respond to the benefits of aspirin therapy. The benefit of aspirin is cardioprotection, or decreasing the risk of heart attack and/or stroke. Aspirin works by disabling the platelets, part of the blood cells used in clotting, from sticking together and forming blood clots, thus protecting the heart. It has been observed that failure to respond to aspirin therapy occurs in about 10% of the general population and that despite taking aspirin everyday, this group of non- responders is not getting protection for their heart. The investigators would like to determine why and how this happens.

Conditions

Aspirin Resistance; Pharmacological Aspirin Non-responsiveness

Keywords

aspirin resistance; cardiovascular risk; prostaglandins; platelet inhibition

Outcome Measures

Primary Outcomes (1)

• Arachidonic acid induced platelet aggregation

  8 hours postdose

Secondary Outcomes (1)

• Serum thromboxane B2 concentration Urinary 11-dehydro thromboxane B2 concentration Urinary 2,3 dinor-6 keto PGF1α concentration

  8 hours postdose

Study Arms (1)

Aspirin

EXPERIMENTAL

single dose of aspirin 325 mg p.o.

Drug: Aspirin

Interventions

Aspirin DRUG

325 mg enteric coated single dose p.o.

Aspirin

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age between 18 - 55
• Subjects must be in good health as based on medical history, physical examination, vital signs, and laboratory tests.
• All subjects must be non- smoking volunteers
• Female subjects of child bearing potential must be using a medically acceptable method of contraception (oral contraception, depo-provera injection, IUD, 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.

You may not qualify if:

• 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 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.
• 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 CABG
• Subjects with renal, hepatic, respiratory, endocrine, metabolic, hematopoietic or neurological disorder.
• 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.

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Institutes of Health (NIH): collaborator
• Bayer: collaborator

Related Publications (1)

• Grosser T, Fries S, Lawson JA, Kapoor SC, Grant GR, FitzGerald GA. Drug resistance and pseudoresistance: an unintended consequence of enteric coating aspirin. Circulation. 2013 Jan 22;127(3):377-85. doi: 10.1161/CIRCULATIONAHA.112.117283. Epub 2012 Dec 4.

  PMID: 23212718 DERIVED

MeSH Terms

Interventions

Aspirin

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Garret A FitzGerald, MD

  University of Pennsylvania, Institute for Translationals Medicine and Therapeutics

  PRINCIPAL INVESTIGATOR

• Susanne Fries, MD

  University of Pennsylvania, Institute for Translationals Medicine and Therapeutics

  PRINCIPAL INVESTIGATOR

• Tilo Grosser, MD

  University of Pennsylvania, Institute for Translationals Medicine and Therapeutics

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 29, 2009
• First Posted: July 30, 2009
• Study Start: September 1, 2004
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: October 15, 2009

Record last verified: 2009-10