Myocardial Reperfusion InjuryPhase 2BQ-123NCT00586820
Role of Endothelin in Microvascular Dysfunction Following PCI for NSTEMI
A Phase 2 study testing BQ-123 in people with Myocardial Reperfusion Injury, run by Mayo Clinic at 1 site in United States.
Trial summary
Percutaneous coronary intervention (PCI) for acute coronary syndromes frequently fails to restore myocardial perfusion despite establishing epicardial vessel patency. Endothelin-1 (ET-1) is a potent vasoconstrictor and its expression is increased in atherosclerotic coronary arteries. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myocardial Reperfusion Injury
- What is being tested?
- BQ-123
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- May 2005to Jan 2012
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Clinical diagnosis of unstable angina or non ST-elevation myocardial infarction, and requiring clinically indicated PCI for the management of non ST elevation acute coronary syndrome.
Who cannot join
- Systemic hypotension (systolic <90 mmHg)
- Heart failure or known ejection fraction < 30%
- Left main disease
- Culprit lesion is in a saphenous vein graft
- 100% occlusion of the culprit vessel or culprit is an ostial right coronary stenosis
- Currently enrolled in other active cardiovascular investigational studies
Show all 10Show fewer
- Severe endocrine, hepatic, or renal disorders
- Pregnancy or lactation
- Federal Medical Center inmates
- Inability or unwillingness to provide informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Role of Endothelin in Microvascular Dysfunction Following Percutaneous Coronary Intervention for Non-ST Elevation Myocardial Infarction
Percutaneous coronary intervention (PCI) for acute coronary syndromes frequently fails to restore myocardial perfusion despite establishing epicardial vessel patency. Endothelin-1 (ET-1) is a potent vasoconstrictor and its expression is increased in atherosclerotic coronary arteries. Our hypothesis is that increased activity of the endogenous endothelin system contributes to microvascular dysfunction, and adjunctive therapy with an endothelin receptor antagonist will result in improved microvascular blood flow.
Aims: The aims of the study are to assess in patients with non ST-elevation myocardial infarction, whether: 1) PCI causes an increase in coronary blood ET-1 level; 2) an endothelin receptor antagonist acutely improves coronary microvascular blood flow following PCI.
Non-ST segment elevation myocardial infarction (NSTEMI) is one type of heart attack. It is defined as the development of heart muscle necrosis results from an acute interruption of blood supply to a part of the heart which is demonstrated by an elevation of cardiac markers Creatinine Kinase Isoenzyme Muscle/Brain Type (CK-MB) in the blood and the absence of ST-segment elevation in ECG (electrocardiography). ST-segment is a portion of ECG, its elevation indicates full thickness damage of heart muscle. Absence of ST-segment elevation in NSTEMI indicates partial thickness damage of heart muscle occurs. Therefore, NSTEMI is less severe type of heart attack compared to STEMI (ST-segment elevation myocardial infarction) in which full thickness damage of heart muscle occurs.
Read the detailed description
Our hypothesis is that the endogenous endothelin system contributes to microvascular dysfunction and impaired myocardial reperfusion following successful PCI for non ST-elevation MI, and that endothelin receptor antagonism will improve microvascular flow. The study will provide new insight into the humoral regulation of the microcirculation in patients presenting with acute coronary syndromes.
General methods: This section describes our approach to investigating the specific aims. The study is a prospective, double blind, placebo-controlled trial to assess the efficacy of a selective endothelin type A receptor antagonist (BQ-123), as adjunctive therapy for PCI for non ST elevation MI. The control group will receive placebo rather than another vasodilator in order to specifically elucidate the role of the endogenous endothelin system.
- Conditions
- Myocardial Reperfusion Injury
- Being tested
- BQ-123, Placebo
- Keywords
- Coronary Atherosclerosis, Microvascular Dysfunction, Non-ST Elevation Myocardial Infarction
- Medical subject headings
- Myocardial Reperfusion Injury, Coronary Artery Disease, Non-ST Elevated Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BQ-123Drug
BQ-123 is a cyclic peptide consisting of five amino acids. BQ-123 will be infused at 300 nmol/min for 20 minutes prior to percutaneous coronary intervention (PCI).
PlaceboDrug
Subjects randomized to the placebo arm will receive a placebo infusion (saline) for 20 minutes prior to PCI.
| Study group | Role | What they receive |
|---|---|---|
| BQ-123 | Experimental | BQ-123 will be infused at 300 nmol/min for 20 minutes prior to percutaneous coronary intervention (PCI). Receives: Drug: BQ-123 |
| Placebo | Placebo comparator | Subjects randomized to the placebo arm will receive a placebo infusion (saline) for 20 minutes prior to PCI. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Average Peak Velocity (APV) Immediately Following Percutaneous Coronary Intervention (PCI)
Coronary microvascular blood flow will be assessed following successful PCI by measuring APV in the culprit vessel using Doppler echocardiography.
Measured: immediately following PCI procedure
Secondary outcomes (1)
Percent Change in Creatinine Kinase Isoenzyme Muscle/Brain Type (CK-MB) From Immediately Pre-PCI to 8 and 16 Hours Post-PCI
CK-MB is a cardiac marker that can demonstrate the development of heart muscle necrosis resulting from an acute interruption of blood supply to a part of the heart. CK-MB is measured by a blood test.
Measured: immediately pre-PCI, 8 hours post-PCI, 16 hours post-PCI
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2008 (estimated)
- Study startMay 2005
- Primary completionJan 2012
- Study completionJan 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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myocardial Reperfusion InjuryStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Amir Lerman, Mayo Clinic
- Investigators
- Abhiram Prasad, M.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00586820
- Sponsor's protocol ID
- 859-05
- Acronym
- BQ-123
- Status last verified
- Jun 2014
- First submitted
- 21 Dec 2007
- Last updated
- 4 Jul 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Guddeti RR, Prasad A, Matsuzawa Y, Aoki T, Rihal C, Holmes D, Best P, Lennon RJ, Lerman LO, Lerman A. Role of endothelin in microvascular dysfunction following percutaneous coronary intervention for non-ST elevation acute coronary syndromes: a single-centre randomised controlled trial. Open Heart. 2016 Aug 4;3(2):e000428. doi: 10.1136/openhrt-2016-000428. eCollection 2016.
PubMed 27547429
Study at a glance
From the registry record, last updated by the sponsor on 4 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Endothelin in Microvascular Dysfunction Following Percutaneous Coronary Intervention for Non-ST Elevation Myocardial Infarction
- ClinicalTrials.gov ID
- NCT00586820
- Acronym / sponsor ID
- BQ-123 / 859-05
- Conditions
- Myocardial Reperfusion Injury
- Keywords
- Coronary Atherosclerosis, Microvascular Dysfunction, Non-ST Elevation Myocardial Infarction
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- May 2005
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 7 Jan 2008 (estimated)
- Results
- Posted 4 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Percutaneous coronary intervention (PCI) for acute coronary syndromes frequently fails to restore myocardial perfusion despite establishing epicardial vessel patency. Endothelin-1 (ET-1) is a potent vasoconstrictor and its expression is increased in atherosclerotic coronary arteries. Our hypothesis is that increased activity of the endogenous endothelin system contributes to microvascular dysfunction, and adjunctive therapy with an endothelin receptor antagonist will result in improved microvascular blood flow.
Aims: The aims of the study are to assess in patients with non ST-elevation myocardial infarction, whether: 1) PCI causes an increase in coronary blood ET-1 level; 2) an endothelin receptor antagonist acutely improves coronary microvascular blood flow following PCI.
Non-ST segment elevation myocardial infarction (NSTEMI) is one type of heart attack. It is defined as the development of heart muscle necrosis results from an acute interruption of blood supply to a part of the heart which is demonstrated by an elevation of cardiac markers Creatinine Kinase Isoenzyme Muscle/Brain Type (CK-MB) in the blood and the absence of ST-segment elevation in ECG (electrocardiography). ST-segment is a portion of ECG, its elevation indicates full thickness damage of heart muscle. Absence of ST-segment elevation in NSTEMI indicates partial thickness damage of heart muscle occurs. Therefore, NSTEMI is less severe type of heart attack compared to STEMI (ST-segment elevation myocardial infarction) in which full thickness damage of heart muscle occurs.
Detailed description
Our hypothesis is that the endogenous endothelin system contributes to microvascular dysfunction and impaired myocardial reperfusion following successful PCI for non ST-elevation MI, and that endothelin receptor antagonism will improve microvascular flow. The study will provide new insight into the humoral regulation of the microcirculation in patients presenting with acute coronary syndromes.
General methods: This section describes our approach to investigating the specific aims. The study is a prospective, double blind, placebo-controlled trial to assess the efficacy of a selective endothelin type A receptor antagonist (BQ-123), as adjunctive therapy for PCI for non ST elevation MI. The control group will receive placebo rather than another vasodilator in order to specifically elucidate the role of the endogenous endothelin system.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BQ-123 | Experimental | Drug: BQ-123BQ-123 will be infused at 300 nmol/min for 20 minutes prior to percutaneous coronary intervention (PCI). |
| Placebo | Placebo comparator | Drug: PlaceboSubjects randomized to the placebo arm will receive a placebo infusion (saline) for 20 minutes prior to PCI. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age ≥ 18 years
- Clinical diagnosis of unstable angina or non ST-elevation myocardial infarction, and requiring clinically indicated PCI for the management of non ST elevation acute coronary syndrome.
Key exclusion criteria (10 listed)
- Systemic hypotension (systolic <90 mmHg)
- Heart failure or known ejection fraction < 30%
- Left main disease
- Culprit lesion is in a saphenous vein graft
- 100% occlusion of the culprit vessel or culprit is an ostial right coronary stenosis
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 |
|---|---|---|
| BQ-123BQ-123 is a cyclic peptide consisting of five amino acids. BQ-123 will be infused at 300 nmol/min for 20 minutes prior to percutaneous coronary intervention (PCI). | Drug | BQ-123 |
| PlaceboSubjects randomized to the placebo arm will receive a placebo infusion (saline) for 20 minutes prior to PCI. | Drug | Placebo |
Primary outcome
Average Peak Velocity (APV) Immediately Following Percutaneous Coronary Intervention (PCI)
Time frame: immediately following PCI procedure
Coronary microvascular blood flow will be assessed following successful PCI by measuring APV in the culprit vessel using Doppler echocardiography.
1 secondary outcome
Percent Change in Creatinine Kinase Isoenzyme Muscle/Brain Type (CK-MB) From Immediately Pre-PCI to 8 and 16 Hours Post-PCI
Time frame: immediately pre-PCI, 8 hours post-PCI, 16 hours post-PCI
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jul 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27547429Guddeti RR, Prasad A, Matsuzawa Y, Aoki T, Rihal C, Holmes D, Best P, Lennon RJ, Lerman LO, Lerman A. Role of endothelin in microvascular dysfunction following percutaneous coronary intervention for non-ST elevation acute coronary syndromes: a single-centre randomised controlled trial. Open Heart. 2016 Aug 4;3(2):e000428. doi: 10.1136/openhrt-2016-000428. eCollection 2016.
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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.
Abhiram Prasad, M.D. principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BQ-123 in people with Myocardial Reperfusion Injury, run by Mayo Clinic 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 2 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: finished, as of the sponsor's last update on 4 Jul 2014. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jul 2014). 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?
Average Peak Velocity (APV) Immediately Following Percutaneous Coronary Intervention (PCI) (time frame: immediately following PCI procedure). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00586820, which also lists 1 linked publication.
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 4 Jul 2014.