Coronary Artery DiseasePhase 2NCT00248066
Safety and Efficacy of RESTEN-MP When Used in Conjunction With a Bare Metal Stent in Coronary Arteries
A Phase 2 study testing RESTEN-MP in people with Coronary Artery Disease and Coronary Restenosis, run by Sarepta Therapeutics, Inc. at 3 sites in Germany.
Trial summary
The process of re-narrowing of a coronary artery following a revascularization procedure such as angioplasty, begins at the time of the procedure. Restenosis has long been considered a major problem for effective long-term interventional success. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease, Coronary Restenosis
- What is being tested?
- RESTEN-MP
- How many people
- 50 participants
- Where
- 3 sitesGermany
- Study dates
- Sep 2005to not given
- 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
- ≥ 18 years of age.
- An acceptable candidate for percutaneous transluminal coronary angioplasty (PTCA), coronary artery stenting, and emergent coronary artery bypass graft (CABG).
- Clinical evidence of ischemic heart disease or a positive functional study.
- The target lesion/vessel must meet the following criteria:
- The target lesion is a single de novo lesion that has not been previously treated with any interventional procedure. Only one lesion may be treated per subject.
- The target vessel must be a native coronary artery with a stenosis of ≥ 50% and < 100%.
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- The target lesion must be ≥ 10 mm and ≤ 30 mm in length.
- The target vessel reference diameter must be ≥ 2.5 mm and ≤ 4.0 mm.
- Female subjects of childbearing potential must have a documented negative serum pregnancy test within seven days before the procedure.
- The subject or the subject's legally authorized representative has been informed of the nature of the study and agrees to its provisions and has provided written informed consent as approved by the Institutional Review Board/Ethics Committee of the respective clinical site.
- The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits.
- The subject is capable of providing informed consent and has provided written consent prior to study entry.
Who cannot join
- Documented left ventricular ejection fraction < 30%.
- Known hypersensitivity or contraindication to aspirin, heparin, ticlopidine, clopidogrel, stainless steel, or sensitivity to contrast media, which cannot be adequately pre-medicated.
- Evidence of an acute myocardial infarction within 72 hours of the intended treatment [defined as: Q wave or non-Q wave infarction having creatine kinase (CK) enzymes ≥ 2 times the upper laboratory normal (with the presence of a CK-MB elevated above the Institution's upper limit of normal)] or acute myocardial infarction in progress at time of treatment.
- Previous coronary interventional procedure of any kind within the 30 days prior to the stent-placement procedure.
- Planned interventional treatment of either the target or any non-target vessel within 30 days post-stent placement procedure is required.
- Target lesion requires treatment with a device other than PTCA prior to stent placement (such as, but not limited to, directional coronary atherectomy, excimer laser, or rotational atherectomy).
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- Previous stenting anywhere in the target vessel.
- Target vessel has evidence of thrombus or is excessively tortuous (2 bends > 90° to reach the target lesion).
- Target lesion has any one of the following characteristics:
- Lesion location is aorto-ostial, an unprotected left main lesion, or within 5 mm of the origin of the left anterior descending coronary artery (LAD), left circumflex coronary artery (LCX), or right coronary artery (RCA);
- Involves a side branch > 2.0 mm in diameter;
- Is at or distal to a 45º bend in the vessel; or
- Is moderately to severely calcified.
- History of a stroke or transient ischemic attack within the prior 6 months.
- Active peptic ulcer or has had upper gastrointestinal (GI) bleeding within the prior 6 months.
- History of a bleeding diathesis or coagulopathy or will refuse blood transfusions.
- Concurrent medical condition with a life expectancy of less than 12 months.
- Any previous or planned treatment with other anti-restenosis therapies including, but not limited to, brachytherapy in the target vessel within 30 days of the stent placement procedure. [Note: Staged treatment of a non-target vessel is appropriate 30 days after enrollment.]
- Currently participating in an investigational drug or another device study that has not completed the primary endpoint or that clinically interferes with the current study endpoints. [Note: Trials requiring extended follow-up for products that were investigational, but have since become commercially available, are not considered investigational trials.]
- Unable to provide informed consent.
Trial locations and contacts
3 sites in 1 country.
Germany3 sites
Coburg Hospital - Cardiology Clinic
Coburg
Cardiology Clinic, University Hospital of Essen
Essen
University Hospital of Heidelberg, Cardiology Clinic
Heidelberg
About this study
Official title: APPRAISAL Trial: A Phase IIa Study to Evaluate the Safety and Preliminary Efficacy of RESTEN-MP® When Used in Conjunction With a Bare Metal Stent in de Novo Native Coronary Artery Lesions
The process of re-narrowing of a coronary artery following a revascularization procedure such as angioplasty, begins at the time of the procedure. Restenosis has long been considered a major problem for effective long-term interventional success. This often results in repeated procedures to deal with recurrent stenosis (or restenosis) of the original targeted vessel.
There is a substantial body of literature suggesting that local MYC protein production in the injured coronary artery is a major stimulus and potential cause of restenosis that appears after stent placement. This study is based upon the hypothesis that stopping MYC protein production in the vessel will help reduce restenosis (vessel re-narrowing).
Read more
AVI BioPharma Inc., has utilized its proprietary antisense chemistry to design a drug that interferes with MYC production.
This study will evaluate the safety and potential effectiveness of RESTEN-MP to reduce in-stent restenosis following balloon angioplasty and stent placement. The post-dose follow-up period is up to six-months.
RESTEN-MP is administered at the time a stent is successfully placed in a coronary artery, and again 24 hours later, via slow-push intravenous administration.
Read the detailed description
The process of restenosis, the re-narrowing of a coronary artery lumen following a revascularization procedure, begins at the time of percutaneous coronary intervention (PCI). Restenosis has long been seen as a major impediment of effective long-term interventional cardiology, necessitating repeated procedures to deal with in situ recurrent stenosis of the original targeted vessel. The restenosis rates are between 30 to 50% of patients treated with balloon angioplasty and between 15 to 30% of patients treated with bare metal stents. There is currently high enthusiasm for drug-eluting stents already approved for the market and which have an overall restenosis rate of < 3% as reported in published reports for most clinical trial patient populations. However, there are subsets of patients (e.g., diabetic patients and patients with diffuse small vessel disease) that have restenosis rates around 10% despite the use of drug-eluting stents. It is probably too early to conclude that the currently approved drug-eluting stents are a panacea to relieve coronary arterial obstruction due to atherosclerotic heart disease. In fact, with the increased usage of the current drug-eluting stents on the market, there are reports of problems such as late stent malposition, subacute and late thromboses, and aneurysm formations due to the vessel toxicity associated with this method of treatment. There remains a definite need for a simple, safe and durable solution to restenosis.
The development of devices such as intravascular ultrasound has led to a greater understanding of restenosis mechanisms, especially after coronary artery stenting. It is presumed that the pathogenesis of coronary artery restenosis after a revascularization procedure entails two major processes. The first component (viz., recoil and remodeling) involves the mechanical collapse and constriction of the treated vessel; however, coronary stents provide luminal scaffolding that eliminates recoil and remodeling. The second component of coronary artery restenosis after a revascularization procedure is the endothelial response to injury. Whereas, the former focus in modulating the pathophysiological mechanisms involved in restenosis centered mainly on inhibition of platelet aggregation and function, current targets of pharmaceutical agents for this condition have shifted to inhibitors of the cell cycle, smooth muscle cell proliferation and migration, synthesis of extra-cellular matrix, and inflammatory mediators. Many different agents are currently being evaluated in pre-clinical and clinical studies.
AVI-4126, the active ingredient of RESTEN-MP, is a proprietary antisense drug designed to interrupt the translation of the human <c-myc> gene by mRNA. Therefore, the basis for this study is to ascertain if RESTEN-MP is safe and has a therapeutic benefit. Slow-push intravenous administration of RESTEN-MP in pharmacological doses in the restenosis porcine model prevented subsequent in-stent stenosis.
This clinical study will evaluate the safety and potential effectiveness of RESTEN-MP to reduce in-stent restenosis following balloon angioplasty. In order to objectively assess the therapeutic value of RESTEN-MP compared to other drugs used in combination with coronary artery stents and to utilize a sensitive method to assess the effectiveness of RESTEN-MP as a neointimal hyperplasia inhibitor, late loss between the time of stent placement and 6 months later is the therapeutic endpoint in this study.
- Conditions
- Coronary Artery Disease, Coronary Restenosis
- Being tested
- RESTEN-MP
- Keywords
- Coronary artery disease, Restenosis, Coronary stent restenosis
- Medical subject headings
- Coronary Artery Disease, Coronary Restenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RESTEN-MPDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the potential efficacy of RESTEN-MP given intravenously upon confirmation of stent implantation and again at 24 hours post-stent implantation
The therapeutic endpoint to assess potential efficacy is the prevention of coronary late lumen loss 6 months after the stent placement procedure, based on quantitative coronary angiography (QCA).
Secondary outcomes (7)
Major adverse cardiac events (MACE) defined as cardiac death, MI (Q wave and non-Q wave), emergent cardiac bypass surgery, and clinically-driven target lesion revascularization (TLR) at Days 14 and 30, and Month 6, 9 and 12 post-stent placement
Target vessel failure (TVF) rate, defined as a composite of target vessel revascularization, recurrent MI (Q or Non Q-Wave), or cardiac death that could not be clearly attributed to a vessel other than the target vessel at Month 9 post-stent placement
Angiographic binary restenosis (≥ 50% diameter stenosis) at Month 6 post-stent placement
In-stent minimum lumen diameter (MLD) at Month 6 post-stent placement
In-segment MLD at Month 6 post-stent placement
Proximal and distal late loss at Month 6 post-stent placement.
In-stent and in-segment percent (%) diameter stenosis at Month 6 post-stent placement
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2005 (estimated)
- Study startSep 2005
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 Sarepta Therapeutics, Inc.The 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants
Sponsor and investigators
- Lead sponsor
- Sarepta Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Baim Institute for Clinical Research
- Investigators
- Stefan Sack, MD, Principal investigator, Cardiac Clinic, University of Essen, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00248066
- Sponsor's protocol ID
- AVI-4126-17
- Status last verified
- Feb 2007
- First submitted
- 1 Nov 2005
- Last updated
- 8 Feb 2007
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- APPRAISAL Trial: A Phase IIa Study to Evaluate the Safety and Preliminary Efficacy of RESTEN-MP® When Used in Conjunction With a Bare Metal Stent in de Novo Native Coronary Artery Lesions
- ClinicalTrials.gov ID
- NCT00248066
- Acronym / sponsor ID
- AVI-4126-17
- Conditions
- Coronary Artery Disease, Coronary Restenosis
- Keywords
- Coronary artery disease, Restenosis, Coronary stent restenosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants
- Lead sponsor
- Sarepta Therapeutics, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Baim Institute for Clinical Research
- Study start
- Sep 2005
- First posted
- 3 Nov 2005 (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 process of re-narrowing of a coronary artery following a revascularization procedure such as angioplasty, begins at the time of the procedure. Restenosis has long been considered a major problem for effective long-term interventional success. This often results in repeated procedures to deal with recurrent stenosis (or restenosis) of the original targeted vessel.
There is a substantial body of literature suggesting that local MYC protein production in the injured coronary artery is a major stimulus and potential cause of restenosis that appears after stent placement. This study is based upon the hypothesis that stopping MYC protein production in the vessel will help reduce restenosis (vessel re-narrowing).
AVI BioPharma Inc., has utilized its proprietary antisense chemistry to design a drug that interferes with MYC production.
This study will evaluate the safety and potential effectiveness of RESTEN-MP to reduce in-stent restenosis following balloon angioplasty and stent placement. The post-dose follow-up period is up to six-months.
RESTEN-MP is administered at the time a stent is successfully placed in a coronary artery, and again 24 hours later, via slow-push intravenous administration.
Detailed description
The process of restenosis, the re-narrowing of a coronary artery lumen following a revascularization procedure, begins at the time of percutaneous coronary intervention (PCI). Restenosis has long been seen as a major impediment of effective long-term interventional cardiology, necessitating repeated procedures to deal with in situ recurrent stenosis of the original targeted vessel. The restenosis rates are between 30 to 50% of patients treated with balloon angioplasty and between 15 to 30% of patients treated with bare metal stents. There is currently high enthusiasm for drug-eluting stents already approved for the market and which have an overall restenosis rate of < 3% as reported in published reports for most clinical trial patient populations. However, there are subsets of patients (e.g., diabetic patients and patients with diffuse small vessel disease) that have restenosis rates around 10% despite the use of drug-eluting stents. It is probably too early to conclude that the currently approved drug-eluting stents are a panacea to relieve coronary arterial obstruction due to atherosclerotic heart disease. In fact, with the increased usage of the current drug-eluting stents on the market, there are reports of problems such as late stent malposition, subacute and late thromboses, and aneurysm formations due to the vessel toxicity associated with this method of treatment. There remains a definite need for a simple, safe and durable solution to restenosis.
The development of devices such as intravascular ultrasound has led to a greater understanding of restenosis mechanisms, especially after coronary artery stenting. It is presumed that the pathogenesis of coronary artery restenosis after a revascularization procedure entails two major processes. The first component (viz., recoil and remodeling) involves the mechanical collapse and constriction of the treated vessel; however, coronary stents provide luminal scaffolding that eliminates recoil and remodeling. The second component of coronary artery restenosis after a revascularization procedure is the endothelial response to injury. Whereas, the former focus in modulating the pathophysiological mechanisms involved in restenosis centered mainly on inhibition of platelet aggregation and function, current targets of pharmaceutical agents for this condition have shifted to inhibitors of the cell cycle, smooth muscle cell proliferation and migration, synthesis of extra-cellular matrix, and inflammatory mediators. Many different agents are currently being evaluated in pre-clinical and clinical studies.
AVI-4126, the active ingredient of RESTEN-MP, is a proprietary antisense drug designed to interrupt the translation of the human <c-myc> gene by mRNA. Therefore, the basis for this study is to ascertain if RESTEN-MP is safe and has a therapeutic benefit. Slow-push intravenous administration of RESTEN-MP in pharmacological doses in the restenosis porcine model prevented subsequent in-stent stenosis.
This clinical study will evaluate the safety and potential effectiveness of RESTEN-MP to reduce in-stent restenosis following balloon angioplasty. In order to objectively assess the therapeutic value of RESTEN-MP compared to other drugs used in combination with coronary artery stents and to utilize a sensitive method to assess the effectiveness of RESTEN-MP as a neointimal hyperplasia inhibitor, late loss between the time of stent placement and 6 months later is the therapeutic endpoint in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- ≥ 18 years of age.
- An acceptable candidate for percutaneous transluminal coronary angioplasty (PTCA), coronary artery stenting, and emergent coronary artery bypass graft (CABG).
- Clinical evidence of ischemic heart disease or a positive functional study.
- The target lesion/vessel must meet the following criteria:
- Female subjects of childbearing potential must have a documented negative serum pregnancy test within seven days before the procedure.
Key exclusion criteria (20 listed)
- Documented left ventricular ejection fraction < 30%.
- Known hypersensitivity or contraindication to aspirin, heparin, ticlopidine, clopidogrel, stainless steel, or sensitivity to contrast media, which cannot be adequately pre-medicated.
- Evidence of an acute myocardial infarction within 72 hours of the intended treatment [defined as: Q wave or non-Q wave infarction having creatine kinase (CK) enzymes ≥ 2 times the upper laboratory normal (with the presence of a CK-MB elevated above the Institution's upper limit of normal)] or acute myocardial infarction in progress at time of treatment.
- Previous coronary interventional procedure of any kind within the 30 days prior to the stent-placement procedure.
- Planned interventional treatment of either the target or any non-target vessel within 30 days post-stent placement procedure is required.
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 |
|---|---|---|
| RESTEN-MP | Drug | – |
Primary outcome
Evaluate the potential efficacy of RESTEN-MP given intravenously upon confirmation of stent implantation and again at 24 hours post-stent implantation
The therapeutic endpoint to assess potential efficacy is the prevention of coronary late lumen loss 6 months after the stent placement procedure, based on quantitative coronary angiography (QCA).
7 secondary outcomes
Major adverse cardiac events (MACE) defined as cardiac death, MI (Q wave and non-Q wave), emergent cardiac bypass surgery, and clinically-driven target lesion revascularization (TLR) at Days 14 and 30, and Month 6, 9 and 12 post-stent placement
Target vessel failure (TVF) rate, defined as a composite of target vessel revascularization, recurrent MI (Q or Non Q-Wave), or cardiac death that could not be clearly attributed to a vessel other than the target vessel at Month 9 post-stent placement
Angiographic binary restenosis (≥ 50% diameter stenosis) at Month 6 post-stent placement
In-stent minimum lumen diameter (MLD) at Month 6 post-stent placement
In-segment MLD at Month 6 post-stent placement
Proximal and distal late loss at Month 6 post-stent placement.
In-stent and in-segment percent (%) diameter stenosis at Month 6 post-stent placement
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 8 Feb 2007.
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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.
Stefan Sack, MD principal investigator
Cardiac Clinic, University of Essen, Germany
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RESTEN-MP in people with Coronary Artery Disease and Coronary Restenosis, run by Sarepta Therapeutics, Inc. at 3 sites in Germany.
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 12 inclusion and 20 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 8 Feb 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Germany. 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 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?
Evaluate the potential efficacy of RESTEN-MP given intravenously upon confirmation of stent implantation and again at 24 hours post-stent implantation. The study lists 2 primary outcomes in all. 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 8 Feb 2007.