Coronary Artery DiseasePhase 3BILLIONNCT01555658
Bivalirudin Plus Stenting in Long Lesion to Avoid Periprocedural Myocardial Necrosis Trial
A Phase 3 study testing Bivalirudin and Unfractioned Heparin in people with Coronary Artery Disease, run by University of Roma La Sapienza at 1 site in Italy.
Trial summary
Background: Randomized trials show improved outcomes among acute coronary syndrome (ACS) patients treated with Bivalirudin1. Optimal antithrombotic treatment in patients undergoing percutaneous coronary intervention (PCI) is crucial to balance the risk of post-PCI bleeding versus ischemic complications2. 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?
- Bivalirudin and Unfractioned Heparin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 204 participants
- Where
- 1 siteItaly
- Study dates
- Apr 2012to Oct 2012
- Phase
- Phase 3
- 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
- Candidates for this study must meet all of the following criteria:
- Male or female able to understand and sign a witnessed informed consent
- Age ≥ 18 yo
- Patients with stable (CCS 1-4) or unstable angina pectoris (but with the most recent anginal episode occurring >48 hours before the index procedure) or documented silent ischemia
- Ongoing or recent episode (<48 hours) of unstable coronary artery disease (including non-ST-elevation acute coronary syndromes)
- Stable Hemodynamic conditions (systolic BP > 100 HR > 40 < 100).
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- No clinical and ECG changes suggestive of ongoing acute or recent (<48 hours) myocardial infarction.
- Angiographic inclusion criteria
- Angiographic evidence of a de novo lesion > 50% requiring implantation of two stents in overlapping with a total stent length> 33 mm and reference vessel diameter between 2.5 and 4.0 mm (by visual estimation) in one coronary vessel. Multiple lesions in the same vessels can be included but at least one lesion should require implantation of two stents in overlapping with a total stent length > 33 mm. The definition of multivessel disease requires an intention to treat at least two lesions (with a least one with the characteristics reported above) in two different major epicardial segments. For example, the presence of a lesion in the left anterior descending artery and in the obtuse marginal or the presence of a lesions in the right postero-lateral branch and in a diagonal branch will qualify as multivessel. The presence of lesions in the left anterior descending artery and in the diagonal branch will not qualify as multivessel. Bifurcation lesions and ostial lesions can be included, but only if at least two stent in overlapping with a total stent length > 33 mm are implanted in the same branch. When treating diffuse lesion in the same vessel, overlapping stenting is recommended with high pressure (>14 atm post-dilation) of the overlap zone. There is no maximum stent length to treat one coronary vessel.
Who cannot join
- Clinical Exclusion criteria
- Female sex with childbearing potential
- Age <18 years
- Serum creatinine>2.5 mg/dl or with a creatinine clearance <40mL/min
- Ongoing serious bleeding or bleeding diathesis
- Previous stroke in the last 6 months
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- Major surgery within the previous 6 weeks
- Platelet count <100,000 per mm3
- Ejection Fraction below 30%
- STEMIpatients' treated with primary-PCI, or rescue-PCI or facilitated-PCI or thrombolysis therapy.
- Patients treated with Glycoprotein IIb/IIIa inhibitor for ACS
- The patient has a known hypersensitivity or contraindication to aspirin, heparin, clopidogrel, or sensitivity to contrast which cannot be adequately pre-medicated.
- Hemodynamic instability (systolic blood pressure < 100 mm Hg; heart rate < 40 bpm or >100 bpm; complex ventricular arrhythmias; AV block) requiring balloon counterpulsation or inotropic support.
- The patient is simultaneously participating in another device or drug study. Patient must have completed the follow-up phase of any previous study at least 30 days prior to enrolment in this study.
- Positive clinical history for intracranial neoplasia, AV malformation, aneurysm.
- INR ≥ 2.0 or prothrombin time 1.2 times upper limit of normality
- Clinically manifested reduced liver function
- Programmed surgery within six months
- Angiographic exclusion criteria
- Vessel size < 2.25 mm or > 5 mm (by visual estimation).
- Previous implantation of a bare-metal or drug-eluting stent in the target lesion
Trial locations and contacts
1 site in 1 country.
Italy1 site
Dept.of Cardiovascular Sciences Policlinico Umberto I
Rome
Rocco E. Stio, MD, rocco.stio@libero.it
Gennaro Sardella, MD
About this study
Background:
Randomized trials show improved outcomes among acute coronary syndrome (ACS) patients treated with Bivalirudin1. Optimal antithrombotic treatment in patients undergoing percutaneous coronary intervention (PCI) is crucial to balance the risk of post-PCI bleeding versus ischemic complications2. Bivalirudin, a direct thrombin inhibitor has been extensively investigated as an intra-procedural antithrombotic therapy in patients with stable angina, Non ST-segment elevation acute coronary syndrome (NSTE-ACS), and ST-segment elevation myocardial infarction (STEMI). Bivalirudin, when used with or without glycoprotein IIb/IIIa inhibitors (GPI) during PCI has been found to be superior to Unfractionated heparin (UFH) with or without GPI in reducing 30-day bleeding complications without significant increase in the rate of ischemic events3-5.
Read more
Moreover,after otherwise successful PCI,an increase in cardiac biomarkers has been shown to occur in 5% to 30% of patients6. Recent studies have focused their attention onthe reduction of infarct size and the incidence of periprocedural (type IVa) myocardial infarction (PMI)after elective PCI7-8. Therefore, we will perform a single-center, prospective and randomized study to assess if Bivalirudin versus UFHis effective in preventing elevation of biomarkers of MI after coronary stent implantation in patients already treated with aspirin and clopidogrel,with anatomically complex lesion.
Objective:
to assess the safety and efficacy of routine usage of the Bivalirudin vs UFH in patients with coronary artery disease (CAD), after stent implantation in coronary long lesions, to avoid periprocedural myocardial necrosis.
Setting:
Single-center, spontaneous, prospective, randomized 1:1 study of Bivalirudin infusion vs UFH in the setting of CAD, after PCI with stenting incoronary long lesions.
Comparison: Bivalirudin vs UFH, in preventing elevation of biomarkers of MI after coronary stent implantation in patients already treated with aspirin and clopidogrel, with anatomically complex lesion.
Population:Patients with diffuse CAD undergoing percutaneous treatment on a native coronary vessel with planned implantation stents in overlapping with a total stent length >33 mm for long coronary lesions in vessels with a reference vessel diameter 2.25-4.0 mm.
Assessment Following the procedure, blood samples for CK, CK-MB and Troponin will be collected at 6,12 and 24 h post PCI. CK-MB values will be considered abnormal if they will elevate above the upper limit of normal (ULN). This is set at 6 mg/L by our local laboratory. If the first blood sample showed a CK-MB level ≥18 mg/L (≥3 times upper normal limit), a second blood sample would be drawn every 8 h later until a downward trend will be observed. For patients with two or more blood samples drawn, the peak CK-MB level will be used for analysis.
End-points:
The primary end-point of this study will be the incidence of periprocedural myonecrosis that was defined as a peak post-procedural CK-MB elevation > 1 time the upper limit of normal (ULN) alone or associated with chest pain or ST-segment or T-wave abnormalities, in patients undergoing non-urgent PCI.
Secondary end-points will be the rate of MACCE (major adverse cerebro-cardiovascular events, ie the composite of death, myocardial infarction [defined according to the Academic Research Consortium statement], target vessel revascularization or stroke), the rate of major bleedings (Bleeding Academic Consortium [BARC] 3-5), minor bleedings (BARC 2), and the rate of NACE (net adverse clinical events, ie the composite of MACCE and major bleedings) at 30 days, 6 and 12 month follow-up. Adverse events will be determined by telephone interview and/or medical record review. Clinical follow-up: telephone-based interviews and office-based direct visits will be performed at 1, 6 and 12 months, respectively, for end-point adjudication.
Sample size and statistical analysis: Given an expected rate of abnormal post-procedural peak CK-MB > 1 x ULM of 48% (based on results of the INSTANT trial) for the control group and 29% for the experimental group (thus a 40% relative risk reduction), aiming for a 0.05 alpha and 0.80 power, a total of 204 patients will need to be enrolled (102 patients per group).
- Conditions
- Coronary Artery Disease
- Being tested
- Bivalirudin, Unfractioned Heparin
- Keywords
- Long Lesions, Stent Implantation
- 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.
BivalirudinDrug
Enrolled patients will be randomized 1:1 in the catheterization laboratory, after the decision to perform PCI by means of planned implantation of stents>33 mm in length in the same coronary vessel, to IV bivalirudin (0.75 mg/kg intravenous bolus followed by 1.75 mg/kg during procedure and 1.25mg/Kg infusion)
Unfractioned HeparinDrug
Enrolled patients will be randomized in the catheterization laboratory, after the decision to perform PCI by means of planned implantation of stents>33 mm in length in the same coronary vessel, to IV UFH (60 IU/kg intravenous bolus followed by boluses with target activated clotting time 200-250 s)
| Study group | Role | What they receive |
|---|---|---|
| Bivalirudin | Experimental | Enrolled patients will be randomized 1:1 in the catheterization laboratory, after the decision to perform PCI by means of planned implantation of stents>33 mm in length in the same coronary vessel, to Bivalirudin Receives: Drug: Bivalirudin |
| Unfractioned Heparin | Experimental | Enrolled patients will be randomized in the catheterization laboratory, after the decision to perform PCI by means of planned implantation of stents>33 mm in length in the same coronary vessel, to Unfractioned Heparin. Receives: Drug: Unfractioned Heparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary end point will be the rate of elevated post-procedural peak CK-MB mass ratio values above the upper limit of normal (ULN, defined as the ratio of the patient's peak value above the ULN)
The primary end-point of this study will be the incidence of periprocedural myonecrosis that was defined as a peak post-procedural CK-MB elevation > 1 time the upper limit of normal (ULN) alone or associated with chest pain or ST-segment or T-wave abnormalities, in patients undergoing non-urgent PCI.
Measured: 30 days
Secondary outcomes (3)
major adverse cerebro-cardiovascular events
Secondary end-points will be the rate of MACCE (major adverse cerebro-cardiovascular events, ie the composite of death, myocardial infarction [defined according to the Academic Research Consortium statement]
Measured: 30 days - 6 and 12 months
major and minor bleedings
In according with Bleeding Academic Consortium (BARC classification)
Measured: 30 days, 6 and 12 months
the rate of net adverse clinical events (NACE)
the composite of MACCE and major bleedings
Measured: 30 days, 6 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2012 (estimated)
- Study startApr 2012
- Primary completionSep 2012 (estimated)
- Study completionOct 2012 (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 University of Roma La SapienzaThe 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 204 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Roma La Sapienza
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gennaro Sardella, University of Roma La Sapienza
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01555658
- Sponsor's protocol ID
- BILLION
- Acronym
- BILLION
- Status last verified
- Mar 2012
- First submitted
- 6 Mar 2012
- Last updated
- 15 Mar 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bivalirudin Plus Stenting in Long Lesion to Avoid Periprocedural Myocardial Necrosis Trial
- ClinicalTrials.gov ID
- NCT01555658
- Acronym / sponsor ID
- BILLION / BILLION
- Conditions
- Coronary Artery Disease
- Keywords
- Long Lesions, Stent Implantation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 204 participants (estimated)
- Lead sponsor
- University of Roma La SapienzaUniversity, hospital or other
- Study start
- Apr 2012
- Primary completion
- Sep 2012 (estimated)
- Study completion
- Oct 2012 (estimated)
- First posted
- 15 Mar 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:
Randomized trials show improved outcomes among acute coronary syndrome (ACS) patients treated with Bivalirudin1. Optimal antithrombotic treatment in patients undergoing percutaneous coronary intervention (PCI) is crucial to balance the risk of post-PCI bleeding versus ischemic complications2. Bivalirudin, a direct thrombin inhibitor has been extensively investigated as an intra-procedural antithrombotic therapy in patients with stable angina, Non ST-segment elevation acute coronary syndrome (NSTE-ACS), and ST-segment elevation myocardial infarction (STEMI). Bivalirudin, when used with or without glycoprotein IIb/IIIa inhibitors (GPI) during PCI has been found to be superior to Unfractionated heparin (UFH) with or without GPI in reducing 30-day bleeding complications without significant increase in the rate of ischemic events3-5.
Moreover,after otherwise successful PCI,an increase in cardiac biomarkers has been shown to occur in 5% to 30% of patients6. Recent studies have focused their attention onthe reduction of infarct size and the incidence of periprocedural (type IVa) myocardial infarction (PMI)after elective PCI7-8. Therefore, we will perform a single-center, prospective and randomized study to assess if Bivalirudin versus UFHis effective in preventing elevation of biomarkers of MI after coronary stent implantation in patients already treated with aspirin and clopidogrel,with anatomically complex lesion.
Objective:
to assess the safety and efficacy of routine usage of the Bivalirudin vs UFH in patients with coronary artery disease (CAD), after stent implantation in coronary long lesions, to avoid periprocedural myocardial necrosis.
Setting:
Single-center, spontaneous, prospective, randomized 1:1 study of Bivalirudin infusion vs UFH in the setting of CAD, after PCI with stenting incoronary long lesions.
Comparison: Bivalirudin vs UFH, in preventing elevation of biomarkers of MI after coronary stent implantation in patients already treated with aspirin and clopidogrel, with anatomically complex lesion.
Population:Patients with diffuse CAD undergoing percutaneous treatment on a native coronary vessel with planned implantation stents in overlapping with a total stent length >33 mm for long coronary lesions in vessels with a reference vessel diameter 2.25-4.0 mm.
Assessment Following the procedure, blood samples for CK, CK-MB and Troponin will be collected at 6,12 and 24 h post PCI. CK-MB values will be considered abnormal if they will elevate above the upper limit of normal (ULN). This is set at 6 mg/L by our local laboratory. If the first blood sample showed a CK-MB level ≥18 mg/L (≥3 times upper normal limit), a second blood sample would be drawn every 8 h later until a downward trend will be observed. For patients with two or more blood samples drawn, the peak CK-MB level will be used for analysis.
End-points:
The primary end-point of this study will be the incidence of periprocedural myonecrosis that was defined as a peak post-procedural CK-MB elevation > 1 time the upper limit of normal (ULN) alone or associated with chest pain or ST-segment or T-wave abnormalities, in patients undergoing non-urgent PCI.
Secondary end-points will be the rate of MACCE (major adverse cerebro-cardiovascular events, ie the composite of death, myocardial infarction [defined according to the Academic Research Consortium statement], target vessel revascularization or stroke), the rate of major bleedings (Bleeding Academic Consortium [BARC] 3-5), minor bleedings (BARC 2), and the rate of NACE (net adverse clinical events, ie the composite of MACCE and major bleedings) at 30 days, 6 and 12 month follow-up. Adverse events will be determined by telephone interview and/or medical record review. Clinical follow-up: telephone-based interviews and office-based direct visits will be performed at 1, 6 and 12 months, respectively, for end-point adjudication.
Sample size and statistical analysis: Given an expected rate of abnormal post-procedural peak CK-MB > 1 x ULM of 48% (based on results of the INSTANT trial) for the control group and 29% for the experimental group (thus a 40% relative risk reduction), aiming for a 0.05 alpha and 0.80 power, a total of 204 patients will need to be enrolled (102 patients per group).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bivalirudin | Experimental | Drug: BivalirudinEnrolled patients will be randomized 1:1 in the catheterization laboratory, after the decision to perform PCI by means of planned implantation of stents>33 mm in length in the same coronary vessel, to Bivalirudin |
| Unfractioned Heparin | Experimental | Drug: Unfractioned HeparinEnrolled patients will be randomized in the catheterization laboratory, after the decision to perform PCI by means of planned implantation of stents>33 mm in length in the same coronary vessel, to Unfractioned Heparin. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female able to understand and sign a witnessed informed consent
- Age ≥ 18 yo
- Patients with stable (CCS 1-4) or unstable angina pectoris (but with the most recent anginal episode occurring >48 hours before the index procedure) or documented silent ischemia
- Ongoing or recent episode (<48 hours) of unstable coronary artery disease (including non-ST-elevation acute coronary syndromes)
- Stable Hemodynamic conditions (systolic BP > 100 HR > 40 < 100).
Key exclusion criteria (21 listed)
- Clinical Exclusion criteria
- Angiographic exclusion criteria
- Vessel size < 2.25 mm or > 5 mm (by visual estimation).
- Previous implantation of a bare-metal or drug-eluting stent in the target lesion
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 |
|---|---|---|
| BivalirudinEnrolled patients will be randomized 1:1 in the catheterization laboratory, after the decision to perform PCI by means of planned implantation of stents>33 mm in length in the same coronary vessel, to IV bivalirudin (0.75 mg/kg intravenous bolus followed by 1.75 mg/kg during procedure and 1.25mg/Kg infusion) | Drug | Bivalirudin |
| Unfractioned HeparinEnrolled patients will be randomized in the catheterization laboratory, after the decision to perform PCI by means of planned implantation of stents>33 mm in length in the same coronary vessel, to IV UFH (60 IU/kg intravenous bolus followed by boluses with target activated clotting time 200-250 s) | Drug | Unfractioned Heparin |
Primary outcome
The primary end point will be the rate of elevated post-procedural peak CK-MB mass ratio values above the upper limit of normal (ULN, defined as the ratio of the patient's peak value above the ULN)
Time frame: 30 days
The primary end-point of this study will be the incidence of periprocedural myonecrosis that was defined as a peak post-procedural CK-MB elevation > 1 time the upper limit of normal (ULN) alone or associated with chest pain or ST-segment or T-wave abnormalities, in patients undergoing non-urgent PCI.
3 secondary outcomes
major adverse cerebro-cardiovascular events
Time frame: 30 days - 6 and 12 months
major and minor bleedings
Time frame: 30 days, 6 and 12 months
the rate of net adverse clinical events (NACE)
Time frame: 30 days, 6 and 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Bivalirudin and Unfractioned Heparin in people with Coronary Artery Disease, run by University of Roma La Sapienza at 1 site in Italy.
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 9 inclusion and 21 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 15 Mar 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 Italy. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Contact Gennaro Sardella, MD (+390649979035, rino.sardella@uniroma1.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary end point will be the rate of elevated post-procedural peak CK-MB mass ratio values above the upper limit of normal (ULN, defined as the ratio of the patient's peak value above the ULN) (time frame: 30 days). 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 15 Mar 2012.