Coronary Artery DiseasePhase 1NCT00868855
Tissue-Type Plasminogen Activator (t-PA) Release Predicts Major Adverse Cardiac Events (MACE) in Patients With Non-critical Coronary Artery Disease
A Phase 1 study testing Bradykinin in people with Coronary Artery Disease, run by Vanderbilt University at 1 site in United States.
Trial summary
Coronary artery disease is the leading cause of death in USA. Contemporary cardiac care has substantially reduced mortality and morbidity in patients with severe coronary artery disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease
- What is being tested?
- Bradykinin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2003to Dec 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >18 year old male and female patients
- All patients are referred for elective cardiac catheterization based on clinical indication
- Cath shows mild or moderate (<70% stenosis) CAD that does not require mechanical intervention
Who cannot join
- Severe stenosis requires intervention.
- Significant left main coronary artery disease (>40%).
- Acute MI or acute coronary syndrome with enzyme elevation or ischemic EKG changes
- Patients with severe left ventricular dysfunction (EF<35%)
- Prior history of myocardial infarction
- History of stroke within 3 months.
Show all 10Show fewer
- Recent history of thrombolytic
- History of coronary intervention within previous 6 months.
- Patients with history of coronary spasm
- Patients with congestive heart failure (class III and IV).
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
Official title: The Intracoronary Tissue-type Plasminogen Activator (t-PA) Release Predicts Major Adverse Cardiac Events in Patients With Non-critical Coronary Artery Disease
Coronary artery disease is the leading cause of death in USA. Contemporary cardiac care has substantially reduced mortality and morbidity in patients with severe coronary artery disease. However, patients with mild to moderate coronary artery stenosis (<70% stenosis) often present in the future with life threatening acute coronary syndrome which carries significant mortality and morbidity. It is difficult to predict outcomes in these patients before the events because the lack of complete understanding of the mechanisms underlying acute coronary syndrome and the lack of reliable markers that will predict major adverse cardiac events (MACE). Tissue-type plasminogen activator (t-PA) is released from endothelial cells and a major factor that prevent thrombosis in the coronary artery, the cause of acute coronary syndrome. Endothelial dysfunction impairs t-PA release. Therefore, we hypothesize that patients with impaired coronary artery t-PA release will have significantly higher risk for future MACE due to intrinsic fibrinolytic dysfunction that leads to increased thrombosis risk.
To test this hypothesis, we will determine whether intrinsic endothelial fibrinolytic dysfunction predicts MACE in patients with non-significant CAD. The study will measure t-PA release mediated by bradykinin, a major mediator for t-PA release. This will involve infusion of bradykinin into left main coronary artery of individuals who have undergone routine cardiac catheterization (clinically indicated). We will take blood samples from the coronary sinus and measure t-PA and plasminogen activator inhibitor-1 antigen and activity levels.
Read the detailed description
Tissue-type Plasminogen Activator (tPA) is a protein in the blood which breaks down clots and plays an important role in preventing myocardial infarction. It is produced by the endothelial cell lining of the blood vessels. Previous studies demonstrate that t-PA is released in response to the hormones bradykinin and acetylcholine. Impaired t-PA release upon bradykinin stimulation may indicate endothelial dysfunction that leads to the development of acute coronary syndrome. In this project, we will determine whether impaired t-PA release can predict future occurrence of acute coronary syndrome. The study will involve individuals getting routine left heart cardiac catheterizations (indication for cardiac catheterization is solely based on clinical indication). Prior to the procedure, patient will have two blood samples (5 ml each) collected from their forearm before and after 2 minutes blood pressure cuff inflation on their arm. After routine diagnostic cardiac catheterization and there is no severe coronary artery stenosis (<70% stenosis), research protocol will be initiated. Study includes infusion with increasing doses of bradykinin into their left main coronary artery, and sample small amounts of blood from their coronary sinus (15 ml total).
- Conditions
- Coronary Artery Disease
- Being tested
- Bradykinin
- Keywords
- Coronary Artery Disease
- Medical subject headings
- Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BradykininDrug
Also called Bachem Distribution Services GmbH-Bradykinin
Bradykinin, 0.2 ug - 2ug/minute, one time intracoronary infusion over 6 minutes. Drug (bradykinin) will be infused into the left main coronary artery via diagnostic catheter (JL4) at an escalating rate of 0.2, 0.6, 2 g/ml (1ml/min). A 5F Multipurpose catheter will be advanced to coronary sinus for blood sampling.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Bradykinin Receives: Drug: Bradykinin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2009 (estimated)
- Study startDec 2003
- Primary completionDec 2010
- Study completionDec 2010
Why it stopped: poor enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Douglas Vaughn, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00868855
- Sponsor's protocol ID
- IRB# 030473
- Other IDs
- 5P5OHL081009-02
- Status last verified
- May 2026
- First submitted
- 19 Mar 2009
- Last updated
- 1 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Intracoronary Tissue-type Plasminogen Activator (t-PA) Release Predicts Major Adverse Cardiac Events in Patients With Non-critical Coronary Artery Disease
- ClinicalTrials.gov ID
- NCT00868855
- Acronym / sponsor ID
- IRB# 030473
- Conditions
- Coronary Artery Disease
- Keywords
- Coronary Artery Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: poor enrollment
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Study start
- Dec 2003
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 25 Mar 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Coronary artery disease is the leading cause of death in USA. Contemporary cardiac care has substantially reduced mortality and morbidity in patients with severe coronary artery disease. However, patients with mild to moderate coronary artery stenosis (<70% stenosis) often present in the future with life threatening acute coronary syndrome which carries significant mortality and morbidity. It is difficult to predict outcomes in these patients before the events because the lack of complete understanding of the mechanisms underlying acute coronary syndrome and the lack of reliable markers that will predict major adverse cardiac events (MACE). Tissue-type plasminogen activator (t-PA) is released from endothelial cells and a major factor that prevent thrombosis in the coronary artery, the cause of acute coronary syndrome. Endothelial dysfunction impairs t-PA release. Therefore, we hypothesize that patients with impaired coronary artery t-PA release will have significantly higher risk for future MACE due to intrinsic fibrinolytic dysfunction that leads to increased thrombosis risk.
To test this hypothesis, we will determine whether intrinsic endothelial fibrinolytic dysfunction predicts MACE in patients with non-significant CAD. The study will measure t-PA release mediated by bradykinin, a major mediator for t-PA release. This will involve infusion of bradykinin into left main coronary artery of individuals who have undergone routine cardiac catheterization (clinically indicated). We will take blood samples from the coronary sinus and measure t-PA and plasminogen activator inhibitor-1 antigen and activity levels.
Detailed description
Tissue-type Plasminogen Activator (tPA) is a protein in the blood which breaks down clots and plays an important role in preventing myocardial infarction. It is produced by the endothelial cell lining of the blood vessels. Previous studies demonstrate that t-PA is released in response to the hormones bradykinin and acetylcholine. Impaired t-PA release upon bradykinin stimulation may indicate endothelial dysfunction that leads to the development of acute coronary syndrome. In this project, we will determine whether impaired t-PA release can predict future occurrence of acute coronary syndrome. The study will involve individuals getting routine left heart cardiac catheterizations (indication for cardiac catheterization is solely based on clinical indication). Prior to the procedure, patient will have two blood samples (5 ml each) collected from their forearm before and after 2 minutes blood pressure cuff inflation on their arm. After routine diagnostic cardiac catheterization and there is no severe coronary artery stenosis (<70% stenosis), research protocol will be initiated. Study includes infusion with increasing doses of bradykinin into their left main coronary artery, and sample small amounts of blood from their coronary sinus (15 ml total).
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: BradykininBradykinin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age >18 year old male and female patients
- All patients are referred for elective cardiac catheterization based on clinical indication
- Cath shows mild or moderate (<70% stenosis) CAD that does not require mechanical intervention
Key exclusion criteria (10 listed)
- Severe stenosis requires intervention.
- Significant left main coronary artery disease (>40%).
- Acute MI or acute coronary syndrome with enzyme elevation or ischemic EKG changes
- Patients with severe left ventricular dysfunction (EF<35%)
- Prior history of myocardial infarction
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 |
|---|---|---|
| BradykininAlso: Bachem Distribution Services GmbH-BradykininBradykinin, 0.2 ug - 2ug/minute, one time intracoronary infusion over 6 minutes. Drug (bradykinin) will be infused into the left main coronary artery via diagnostic catheter (JL4) at an escalating rate of 0.2, 0.6, 2 g/ml (1ml/min). A 5F Multipurpose catheter will be advanced to coronary sinus for blood sampling. | Drug | 1 |
Primary outcome
Mortality
Time frame: 5 years
Results and safety
The study was stopped early (reason given: poor enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2026.
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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.
Douglas Vaughn, MD principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Bradykinin in people with Coronary Artery Disease, run by Vanderbilt University 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 3 inclusion and 10 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: stopped early, as of the sponsor's last update on 1 Jun 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: poor enrollment). Results are not available in the source record.
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?
Mortality (time frame: 5 years). 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 1 Jun 2026.