Coronary RestenosisPhase 2NCT01269242
The Effects of Bindarit in Preventing Stent Restenosis
A Phase 2 study testing bindarit in people with Coronary Restenosis, run by Aziende Chimiche Riunite Angelini Francesco S.p.A at 1 site in Italy.
Trial summary
The main study objective is to assess the efficacy and safety of different bindarit dosages compared to placebo in preventing restenosis, in patients submitted to coronary stenting and using a bare metal stent (Vision BMS, by Abbott). Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Coronary Restenosis
- What is being tested?
- bindarit
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 148 participants
- Where
- 1 siteItaly
- Study dates
- Jan 2009to Apr 2011
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female patients with no limitation of race, > 18 years of age (or minimum age as required by local regulations). Female patients of childbearing potential, required to have a negative pregnancy test and use a birth control method. Oral contraceptive are not allowed.
- Diagnosis of angina pectoris as defined by Canadian Cardiovascular Society Classification (CCS I,II, III, IV) OR unstable angina pectoris (Braunwald Classification B\&C, I-II-III), or patients with documented silent ischemia.
- Maximum of two de novo lesions (>70% stenosis) per patients, to be treated with no other planned procedure within six months from the index intervention.
- Each lesion should require a single stent not longer than 28 mm and with a diameter of 2.5 mm or larger. In case additional stents are needed, the operator will be allowed to implant them in order to treat a suboptimal result such as residual edge stenosis or dissection. Additional stents should be implanted with minimal overlap. Multiple stenting should not be allowed as intention to treat strategy due to the specific inclusion criteria which has been set.
- Patients eligible for the placement of the Vision (Abbott) bare metal stent.
- The patient willing and able to cooperate with the protocol procedures, particularly attending the scheduled visits.
- Patients legally able to give written informed consent to the trial.
- A written informed consent to the trial signed and dated by the patient is available.
Who cannot join
- Patients with hypersensitivity or allergies to aspirin, heparin, clopidogrel, ticlopidine, drugs such the study medication, or any other analogue or derivative, cobalt, chromium, nickel, molybdenum or contrast media, or with a positive history for drug allergy.
- Lesions in venous or arterial grafts.
- Total occlusions.
- In-stent restenosis.
- Unprotected Left Main lesions.
- Acute myocardial infarction (ST elevation and/or Non ST Elevation) in the 48 hours prior to the procedure.
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- Women with known pregnancy or who are lactating.
- Patients in whom anti-platelet and/or anticoagulation therapy is contraindicated.
- Current medical condition with a life expectancy of less than 24 months.
- The subject is participating in another device or drug study. Subject must have completed the follow-up phase of any previous study at least 30 days prior to enrolment in this trial.
- Patients under the influence of alcohol or narcotics.
- Patients with medical conditions that preclude the follow-up as defined in the protocol or that otherwise limits participation in this registry.
- Potassium value above the upper limit normal range.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Fondazione S.Raffaele del Monte Tabor - UO Emodinamica e Cardiologia Interventistica
Milan, Milan, 20132
About this study
Official title: A Pilot Study to Evaluate the Efficacy and Safety of Different Bindarit Dosages in Preventing Stent Restenosis
The main study objective is to assess the efficacy and safety of different bindarit dosages compared to placebo in preventing restenosis, in patients submitted to coronary stenting and using a bare metal stent (Vision BMS, by Abbott).
Read the detailed description
Coronary artery disease is caused by the gradual build-up of fatty deposits in coronary arteries (atherosclerosis). A diminished blood flow may cause chest pain (angina), shortness of breath or other symptoms. A complete blockage can cause a heart attack. Angioplasty and stenting techniques are safe and effective procedures performed to unblock coronary arteries. However, a recurrent problem after angioplasty is the occurrence of a new blockage, usually within 6 to 9 months after the initial procedure. This phenomenon, called "restenosis", is a body's response to the injury of the angioplasty and does not mean a progression of coronary artery disease.The pathophysiology of restenosis is complex and has as yet not been fully clarified.
Serial studies have shown that in-stent restenosis is almost exclusively caused by neointimal hyperplasia and tissue proliferation occurring in site or adjacent to the stent sites. Histological studies confirmed that neointimal hyperplasia post-stent implantation is related to vessel injury during the procedure. Chemokines have been implicated in the pathogenesis of vascular injury. In this context, MCP-1 which shows a potent chemotactic action on monocytes, can amplify the inflammatory response through the recruitment of additional monocytes. In addition, MCP-3 is known to share some key biological features with MCP-1. It has been proved that MCP-1 directly induces human vascular smooth muscle proliferation acting at this level as a potent mitogen, and that anti-MCP-1 gene therapy inhibits restenotic changes (neointimal hyperplasia) in animals after balloon injury.
An evidence of a critical increase in circulating MCP-1 after coronary angioplasty was reported. It was more evident and prolonged in patients with restenosis rather than in non-restenotic patients, in which only a transient increases in plasma MCP-1 has been demonstrated.
Since these chemokines showed to play a main role in the appearance and worsening of the restenosis process, a selective inhibitor of MCP-1 and other members of monocyte chemotactic protein subfamily of CC inflammatory chemokines (MCP-3/CCL7, MCP-2/CCL8), such as bindarit, may have a potential therapeutic use in preventing restenosis by inhibiting the VSMC proliferation, and without affecting the important process of re-endothelization.
- Conditions
- Coronary Restenosis
- Being tested
- bindarit, placebo
- Keywords
- coronary restenosis, angioplasty, stent, MCP-1/CCL2, MCP-3/CCL7
- Medical subject headings
- Coronary Restenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bindaritDrug
300 mg bid, that is one 300 mg tablet twice a day for 6 months;
bindaritDrug
600 mg bid, that is two 300 mg tablets twice a day for 6 months
placeboDrug
bindarit-matching placebo tablets for 6 months.
| Study group | Role | What they receive |
|---|---|---|
| bindarit 600 mg | Experimental | Not described Receives: Drug: bindarit |
| bindarit 1200 mg | Experimental | Not described Receives: Drug: bindarit |
| placebo | Placebo comparator | Not described Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
in-segment late loss (in-stent and 5 mm proximally and distally to the stent) measured by QCA
Late loss is defined as the difference between post-procedural minimum lumen diameter and 6-month minimum lumen diameter measured in-stent and in-segment.
Measured: 6 months from the index procedure
Secondary outcomes (4)
Major Adverse Cardiac Events (MACE)
MACE are defined as the occurrence of death, Myocardial Infarction (MI), target vessel revascularization and target lesion revascularization(CABG or PTCA).
Measured: 9 months
the assessment of the safety profile of the two bindarit dosages compared to placebo
Safety will be assessed by monitoring the frequency of adverse events in each treatment group. Changes from baseline in physical examination, vital signs, and ECG will be also assessed. Laboratory analyses will be evaluated on the basis of the normal range, the Investigator's judgement, and mean changes from baseline (when applicable).
Measured: 9 months
the imaging parameters evaluated with OCT as an optional procedure performed on a subgroup of patients.
The following parameters will be evaluated:
- the neointimal proliferation on the surface of the stent struts;
- the frequency of stent malapposition.
Measured: 6 months from the index procedure
the assessment of inflammatory biomarkers in order to investigate the bindarit mechanism of action.
determination of the plasma levels of several circulating inflammatory biomarkers (i.e. MCP-1/CCL-2, MCP-3/CCL7) involved in the neointimal hyperplasia and tissue proliferation occurring in site or adjacent to the stent sites.
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2011 (estimated)
- Study startJan 2009
- Primary completionJan 2011
- Study completionApr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary RestenosisStudies 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 148 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aziende Chimiche Riunite Angelini Francesco S.p.A
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Antonio Colombo, MD, Study chair, Fondazione S.Raffaele del Monte Tabor - U.O Emodinamica e Cardiologia Interventistica
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01269242
- Sponsor's protocol ID
- 004SC08166
- Other IDs
- 2008-004921-40, 2008
- Status last verified
- Aug 2016
- First submitted
- 3 Jan 2011
- Last updated
- 5 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Evaluate the Efficacy and Safety of Different Bindarit Dosages in Preventing Stent Restenosis
- ClinicalTrials.gov ID
- NCT01269242
- Acronym / sponsor ID
- 004SC08166
- Conditions
- Coronary Restenosis
- Keywords
- coronary restenosis, angioplasty, stent, MCP-1/CCL2, MCP-3/CCL7
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 148 participants (actual)
- Lead sponsor
- Aziende Chimiche Riunite Angelini Francesco S.p.AIndustry (pharma, biotech, devices)
- Study start
- Jan 2009
- Primary completion
- Jan 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 4 Jan 2011 (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.
The main study objective is to assess the efficacy and safety of different bindarit dosages compared to placebo in preventing restenosis, in patients submitted to coronary stenting and using a bare metal stent (Vision BMS, by Abbott).
Detailed description
Coronary artery disease is caused by the gradual build-up of fatty deposits in coronary arteries (atherosclerosis). A diminished blood flow may cause chest pain (angina), shortness of breath or other symptoms. A complete blockage can cause a heart attack. Angioplasty and stenting techniques are safe and effective procedures performed to unblock coronary arteries. However, a recurrent problem after angioplasty is the occurrence of a new blockage, usually within 6 to 9 months after the initial procedure. This phenomenon, called "restenosis", is a body's response to the injury of the angioplasty and does not mean a progression of coronary artery disease.The pathophysiology of restenosis is complex and has as yet not been fully clarified.
Serial studies have shown that in-stent restenosis is almost exclusively caused by neointimal hyperplasia and tissue proliferation occurring in site or adjacent to the stent sites. Histological studies confirmed that neointimal hyperplasia post-stent implantation is related to vessel injury during the procedure. Chemokines have been implicated in the pathogenesis of vascular injury. In this context, MCP-1 which shows a potent chemotactic action on monocytes, can amplify the inflammatory response through the recruitment of additional monocytes. In addition, MCP-3 is known to share some key biological features with MCP-1. It has been proved that MCP-1 directly induces human vascular smooth muscle proliferation acting at this level as a potent mitogen, and that anti-MCP-1 gene therapy inhibits restenotic changes (neointimal hyperplasia) in animals after balloon injury.
An evidence of a critical increase in circulating MCP-1 after coronary angioplasty was reported. It was more evident and prolonged in patients with restenosis rather than in non-restenotic patients, in which only a transient increases in plasma MCP-1 has been demonstrated.
Since these chemokines showed to play a main role in the appearance and worsening of the restenosis process, a selective inhibitor of MCP-1 and other members of monocyte chemotactic protein subfamily of CC inflammatory chemokines (MCP-3/CCL7, MCP-2/CCL8), such as bindarit, may have a potential therapeutic use in preventing restenosis by inhibiting the VSMC proliferation, and without affecting the important process of re-endothelization.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| bindarit 600 mg | Experimental | Drug: bindarit |
| bindarit 1200 mg | Experimental | Drug: bindarit |
| placebo | Placebo comparator | Drug: placebo |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male and female patients with no limitation of race, > 18 years of age (or minimum age as required by local regulations). Female patients of childbearing potential, required to have a negative pregnancy test and use a birth control method. Oral contraceptive are not allowed.
- Diagnosis of angina pectoris as defined by Canadian Cardiovascular Society Classification (CCS I,II, III, IV) OR unstable angina pectoris (Braunwald Classification B\&C, I-II-III), or patients with documented silent ischemia.
- Maximum of two de novo lesions (>70% stenosis) per patients, to be treated with no other planned procedure within six months from the index intervention.
- Each lesion should require a single stent not longer than 28 mm and with a diameter of 2.5 mm or larger. In case additional stents are needed, the operator will be allowed to implant them in order to treat a suboptimal result such as residual edge stenosis or dissection. Additional stents should be implanted with minimal overlap. Multiple stenting should not be allowed as intention to treat strategy due to the specific inclusion criteria which has been set.
- Patients eligible for the placement of the Vision (Abbott) bare metal stent.
Key exclusion criteria (13 listed)
- Patients with hypersensitivity or allergies to aspirin, heparin, clopidogrel, ticlopidine, drugs such the study medication, or any other analogue or derivative, cobalt, chromium, nickel, molybdenum or contrast media, or with a positive history for drug allergy.
- Lesions in venous or arterial grafts.
- Total occlusions.
- In-stent restenosis.
- Unprotected Left Main lesions.
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 |
|---|---|---|
| bindarit300 mg bid, that is one 300 mg tablet twice a day for 6 months; | Drug | bindarit 600 mg |
| bindarit600 mg bid, that is two 300 mg tablets twice a day for 6 months | Drug | bindarit 1200 mg |
| placebobindarit-matching placebo tablets for 6 months. | Drug | placebo |
Primary outcome
in-segment late loss (in-stent and 5 mm proximally and distally to the stent) measured by QCA
Time frame: 6 months from the index procedure
Late loss is defined as the difference between post-procedural minimum lumen diameter and 6-month minimum lumen diameter measured in-stent and in-segment.
4 secondary outcomes
Major Adverse Cardiac Events (MACE)
Time frame: 9 months
the assessment of the safety profile of the two bindarit dosages compared to placebo
Time frame: 9 months
the imaging parameters evaluated with OCT as an optional procedure performed on a subgroup of patients.
Time frame: 6 months from the index procedure
the assessment of inflammatory biomarkers in order to investigate the bindarit mechanism of action.
Time frame: 9 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2016.
- Sponsor websiteLink provided by the sponsor.
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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.
Antonio Colombo, MD study chair
Fondazione S.Raffaele del Monte Tabor - U.O Emodinamica e Cardiologia Interventistica
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 bindarit in people with Coronary Restenosis, run by Aziende Chimiche Riunite Angelini Francesco S.p.A 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 8 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: finished, as of the sponsor's last update on 5 Aug 2016. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
in-segment late loss (in-stent and 5 mm proximally and distally to the stent) measured by QCA (time frame: 6 months from the index procedure). 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 5 Aug 2016.