Coronary Artery DiseasePhase 2NCT01658410
Short-term Endothelin A Receptor Blockade in Patients With On-pump CABG
A Phase 2 study testing BQ-123 and NaCl in people with Coronary Artery Disease and Aorto-coronary Bypass Grafting, run by Medical University of Vienna at 1 site in Austria.
Trial summary
Background: Although selected cardiac surgery can be performed off-pump, the vast majority of cardiac surgical procedures today are performed with the support of cardiopulmonary bypass (CPB). Blood cardioplegia is used to protect the heart during aortic cross-clamping. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease, Aorto-coronary Bypass Grafting
- What is being tested?
- BQ-123 and NaCl
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteAustria
- Study dates
- Jul 2012to Dec 2016
- Phase
- Phase 2
- 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
- Patients undergoing on-pump coronary artery bypass grafting using the left mammary artery to the left anterior descendent artery and at least one vein graft due to coronary artery disease, aged 18 years and above.
Who cannot join
- Significant liver disease (Transaminases and/or gamma-GT > 3 fold upper limit)
- Glomerular filtration rate <40mL/h
- History of severe congestive heart failure (Left ventricular ejection fraction <35%)
- Current atrial fibrillation
- Significant valvular heart disease requiring valve replacement Department of Cardiac Surgery
- Primary myocardial disease
Show all 13Show fewer
- Acute coronary syndrome or cardiogenic shock (sRR <90mmHg or need for inotropic support)
- Women with child-bearing potential
- Subjects with contraindications for CMR (cardiac magnetic resonance)
- Inability to read, understand and sign the informed consent
- Life expectancy <1y
- Prior organ transplantation
- Participation in a clinical trial using an investigational medical product
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Short-term Endothelin A Receptor Blockade in Patients With On-pump Coronary Artery Bypass Grafting
Background: Although selected cardiac surgery can be performed off-pump, the vast majority of cardiac surgical procedures today are performed with the support of cardiopulmonary bypass (CPB). Blood cardioplegia is used to protect the heart during aortic cross-clamping. However, negative effects of myocardial hypoxia during surgery are often aggravated by ischemia/reperfusion injury. In addition, cardiopulmonary bypass leads to an inflammatory response including endothelial cell activation.
Comparable to the reperfusion injury following acute myocardial infarction resolved by percutaneous coronary intervention, the microcirculatory impairment observed after cardiac surgery may be caused by endothelin 1 (ET-1). ET-1 is a potent vasoconstrictor peptide upregulated in myocardial ischemia-reperfusion injury. Short-term administration of the selective ETA receptor blocker BQ-123 was found safe in a pilot study including patients with acute myocardial infarction.
Read more
Hypothesis: Acute local ETA receptor blockade by intracoronary administered BQ-123 reduces myocardial injury.
Methods: BQ-123 will be administered in patients undergoing on-pump aorto-coronary bypass grafting to the left anterior descending coronary artery with the use a left inner mammary artery graft and at least one vein graft. Subjects will be randomized to receive the endothelin-A receptor blocker BQ-123 or placebo administered intracoronarily in combination with cardioplegia in a double-blind manner. The primary endpoint will be enzymatic infarct size.
Clinical perspective: The implementation of BQ-123 as an add-on pharmacologic therapy in cardiac surgery performed with the use of cardiopulmonary bypass could lead to improved tissue reperfusion and reduced ischemia/reperfusion injury, potentially impacting clinical long-term outcome.
Read the detailed description
Background: Although selected cardiac surgery can be performed off-pump, the vast majority of cardiac surgical procedures today are performed with the support of cardiopulmonary bypass (CPB). Blood cardioplegia is used to protect the heart during aortic cross-clamping. However, negative effects of myocardial hypoxia during surgery are often aggravated by ischemia/reperfusion injury. In addition, cardiopulmonary bypass leads to an inflammatory response including endothelial cell activation.
Comparable to the reperfusion injury following acute myocardial infarction resolved by percutaneous coronary intervention, the microcirculatory impairment observed after cardiac surgery may be caused by endothelin 1 (ET-1). ET-1 is a potent vasoconstrictor peptide upregulated in myocardial ischemia-reperfusion injury. Short-term administration of the selective ETA receptor blocker BQ-123 was found safe in a pilot study including patients with acute myocardial infarction. Patients with posterior-wall STE-ACS (n=57) were randomly assigned to receive intravenous BQ-123 at 400nmol/minute or placebo over 60 minutes, starting immediately prior to primary percutaneous coronary intervention (PCI). No side branch occlusions, bleeding complications or severe systemic hypotensive episodes occurred and all patients were alive at 30 days.
Hypothesis: Acute local ETA receptor blockade by intracoronary administered BQ-123 reduces myocardial injury.
Methods: BQ-123 will be administered in patients undergoing on-pump aorto-coronary bypass grafting to the left anterior descending coronary artery with the use a left inner mammary artery graft and at least one vein graft. After a 1:1 randomized pilot safety-phase with 30 patients administering half the dose, 90 subjects will be randomized to receive 15µmol BQ-123 dissolved in NaCl 0.9% or placebo (NaCl 0.9% ) administered intracoronarily in combination with cardioplegia in a double-blind manner. The primary endpoint will be enzymatic infarct size assessed by the area under the curve of myocard specific creatine kinase-MB isoform (CK-MB). Left ventricular ejection fraction, diastolic dysfunction and, perioperative echocardiography, postoperative levels of myeloperoxidase and matrixmetalloproteinase-9 activity as well as MACE will serve as secondary endpoints.
Clinical perspective: The implementation of BQ-123 as an add-on pharmacologic therapy in cardiac surgery performed with the use of cardiopulmonary bypass could lead to improved tissue reperfusion and reduced ischemia/reperfusion injury, potentially impacting clinical long-term outcome.
- Being tested
- BQ-123, NaCl
- Keywords
- Coronary artery disease, bypass grafting
- 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.
BQ-123Drug
Also called Cyclo(-D-Trp-D-Asp-Pro-D-Val-Leu) sodium salt
BQ-123 (Clinalfa, Läufelfingen, Switzerland) Dosage: 15µmol in two equal amounts (7.5µmol); in the first and last cardioplegia Route: intracoronary
NaClDrug
NaCl, Route: intracoronary
| Study group | Role | What they receive |
|---|---|---|
| BQ-123 | Active comparator | Not described Receives: Drug: BQ-123 |
| NaCl | Placebo comparator | Not described Receives: Drug: NaCl |
What is being measured
The primary outcome is the main question the study is designed to answer.
enzymatic infarct size
Measured: 72h
Secondary outcomes (3)
Catecholamines
Measured: 5h
Liver function
Measured: 72h
catecholamine requirement
Measured: 72h
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2012 (estimated)
- Study startJul 2012
- Primary completionDec 2015 (estimated)
- Study completionDec 2016 (estimated)
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.
- More trials run by Medical University of ViennaThe 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, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alfred A Kocher, MD, Medical University of Vienna
- Investigators
- Alfred Kocher, MD, Principal investigator, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01658410
- Sponsor's protocol ID
- 2010-023552-90
- Status last verified
- Aug 2012
- First submitted
- 26 Jul 2012
- Last updated
- 7 Aug 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short-term Endothelin A Receptor Blockade in Patients With On-pump Coronary Artery Bypass Grafting
- ClinicalTrials.gov ID
- NCT01658410
- Acronym / sponsor ID
- 2010-023552-90
- Keywords
- Coronary artery disease, bypass grafting
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- Jul 2012
- Primary completion
- Dec 2015 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 7 Aug 2012 (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.
Background: Although selected cardiac surgery can be performed off-pump, the vast majority of cardiac surgical procedures today are performed with the support of cardiopulmonary bypass (CPB). Blood cardioplegia is used to protect the heart during aortic cross-clamping. However, negative effects of myocardial hypoxia during surgery are often aggravated by ischemia/reperfusion injury. In addition, cardiopulmonary bypass leads to an inflammatory response including endothelial cell activation.
Comparable to the reperfusion injury following acute myocardial infarction resolved by percutaneous coronary intervention, the microcirculatory impairment observed after cardiac surgery may be caused by endothelin 1 (ET-1). ET-1 is a potent vasoconstrictor peptide upregulated in myocardial ischemia-reperfusion injury. Short-term administration of the selective ETA receptor blocker BQ-123 was found safe in a pilot study including patients with acute myocardial infarction.
Hypothesis: Acute local ETA receptor blockade by intracoronary administered BQ-123 reduces myocardial injury.
Methods: BQ-123 will be administered in patients undergoing on-pump aorto-coronary bypass grafting to the left anterior descending coronary artery with the use a left inner mammary artery graft and at least one vein graft. Subjects will be randomized to receive the endothelin-A receptor blocker BQ-123 or placebo administered intracoronarily in combination with cardioplegia in a double-blind manner. The primary endpoint will be enzymatic infarct size.
Clinical perspective: The implementation of BQ-123 as an add-on pharmacologic therapy in cardiac surgery performed with the use of cardiopulmonary bypass could lead to improved tissue reperfusion and reduced ischemia/reperfusion injury, potentially impacting clinical long-term outcome.
Detailed description
Background: Although selected cardiac surgery can be performed off-pump, the vast majority of cardiac surgical procedures today are performed with the support of cardiopulmonary bypass (CPB). Blood cardioplegia is used to protect the heart during aortic cross-clamping. However, negative effects of myocardial hypoxia during surgery are often aggravated by ischemia/reperfusion injury. In addition, cardiopulmonary bypass leads to an inflammatory response including endothelial cell activation.
Comparable to the reperfusion injury following acute myocardial infarction resolved by percutaneous coronary intervention, the microcirculatory impairment observed after cardiac surgery may be caused by endothelin 1 (ET-1). ET-1 is a potent vasoconstrictor peptide upregulated in myocardial ischemia-reperfusion injury. Short-term administration of the selective ETA receptor blocker BQ-123 was found safe in a pilot study including patients with acute myocardial infarction. Patients with posterior-wall STE-ACS (n=57) were randomly assigned to receive intravenous BQ-123 at 400nmol/minute or placebo over 60 minutes, starting immediately prior to primary percutaneous coronary intervention (PCI). No side branch occlusions, bleeding complications or severe systemic hypotensive episodes occurred and all patients were alive at 30 days.
Hypothesis: Acute local ETA receptor blockade by intracoronary administered BQ-123 reduces myocardial injury.
Methods: BQ-123 will be administered in patients undergoing on-pump aorto-coronary bypass grafting to the left anterior descending coronary artery with the use a left inner mammary artery graft and at least one vein graft. After a 1:1 randomized pilot safety-phase with 30 patients administering half the dose, 90 subjects will be randomized to receive 15µmol BQ-123 dissolved in NaCl 0.9% or placebo (NaCl 0.9% ) administered intracoronarily in combination with cardioplegia in a double-blind manner. The primary endpoint will be enzymatic infarct size assessed by the area under the curve of myocard specific creatine kinase-MB isoform (CK-MB). Left ventricular ejection fraction, diastolic dysfunction and, perioperative echocardiography, postoperative levels of myeloperoxidase and matrixmetalloproteinase-9 activity as well as MACE will serve as secondary endpoints.
Clinical perspective: The implementation of BQ-123 as an add-on pharmacologic therapy in cardiac surgery performed with the use of cardiopulmonary bypass could lead to improved tissue reperfusion and reduced ischemia/reperfusion injury, potentially impacting clinical long-term outcome.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BQ-123 | Active comparator | Drug: BQ-123 |
| NaCl | Placebo comparator | Drug: NaCl |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients undergoing on-pump coronary artery bypass grafting using the left mammary artery to the left anterior descendent artery and at least one vein graft due to coronary artery disease, aged 18 years and above.
Key exclusion criteria (13 listed)
- Significant liver disease (Transaminases and/or gamma-GT > 3 fold upper limit)
- Glomerular filtration rate <40mL/h
- History of severe congestive heart failure (Left ventricular ejection fraction <35%)
- Current atrial fibrillation
- Significant valvular heart disease requiring valve replacement Department of Cardiac Surgery
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-123Also: Cyclo(-D-Trp-D-Asp-Pro-D-Val-Leu) sodium saltBQ-123 (Clinalfa, Läufelfingen, Switzerland) Dosage: 15µmol in two equal amounts (7.5µmol); in the first and last cardioplegia Route: intracoronary | Drug | BQ-123 |
| NaClNaCl, Route: intracoronary | Drug | NaCl |
Primary outcome
enzymatic infarct size
Time frame: 72h
3 secondary outcomes
Catecholamines
Time frame: 5h
Liver function
Time frame: 72h
catecholamine requirement
Time frame: 72h
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2012.
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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.
Alfred Kocher, MD principal investigator
Medical University of Vienna
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 and NaCl in people with Coronary Artery Disease and Aorto-coronary Bypass Grafting, run by Medical University of Vienna at 1 site in Austria.
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 1 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: status not confirmed, as of the sponsor's last update on 7 Aug 2012. 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 Austria. 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?
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?
enzymatic infarct size (time frame: 72h). 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 7 Aug 2012.