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Phase 4 N=597 Randomized Triple-blind Treatment

Drug-Eluting Stents vs. Bare Metal Stents In Saphenous Vein Graft Angioplasty

Saphenous Vein Graft Atherosclerosis

Enrolled (actual)
597
Serious AEs
79.6%
Results posted
Feb 2018
Primary outcome: Primary: Number of Participants With Target Vessel Failure (TVF), Defined as the Composite of Cardiac Death — 16; 17 Participants

Study Design & Population

Study type
Interventional
Phase
Phase 4
Interventions
Bare Metal Stent (Device); Drug-Eluting Stent (Device); Blinded clopidogrel (Drug); Placebo (Drug); Thienopyridine (open-label) (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
VA Office of Research and Development
Primary completion
Dec 2016

Outcome Measures

OutcomeResultp-value
PRIMARY
Number of Participants With Target Vessel Failure (TVF), Defined as the Composite of Cardiac Death
16; 17
PRIMARY
Number of Participants With Target Vessel Failure (TVF), Defined as the Target Vessel Myocardial Infarction
20; 16
PRIMARY
Number of Participants With Target Vessel Failure (TVF), Defined as the Target Vessel Revascularization
34; 34
SECONDARY
Incremental Cost-effectiveness of DES Relative to BMS
20939; 21051
SECONDARY
Procedural Success
291; 274
SECONDARY
Number of Participant Deaths (All Cause and Cardiac). All Deaths Will be Considered Cardiac Unless an Unequivocal Non-cardiac Cause Can be Established.
51; 55
SECONDARY
Number of Participants With Myocardial Infarction (MI)
62; 53
SECONDARY
Number of Participants With Definite Stent Thrombosis as Defined Using the Academic Research Consortium (ARC) Definition
7; 6
SECONDARY
Number of Participants With Target Vessel Revascularization (TVR)
105; 108
SECONDARY
Patient-Oriented Composite Endpoint Will be Used as Secondary Outcome
68; 62
SECONDARY
In Patients Who Clinically Require Follow-up Angiography, Two Angiographic Endpoints Will be Assessed: (a) In-segment Binary Restenosis and (b) Angiographic Late In-segment Luminal Loss.
1.05; 0.96
SECONDARY
Number of Participants With Stroke
12; 10
SECONDARY
Incremental Cost-effectiveness Ratios (ICERs) for Subgroups of Patients, Such as Those With Highest Risk of Restenosis, Tallies of Cost by Type, and a Cost-outcomes Analysis Such as Cost Per Restenosis Avoided.
-2578.71; -2971.90; -17998.43; -11768.06; -5069.18; -14152
SECONDARY
In-stent Neointima Proliferation as Measured by Intravascular Ultrasonography
SECONDARY
Number of Participants With Target Lesion Revascularization (TLR)
40; 47
SECONDARY
Number of Participants With Target Vessel Myocardial Infarction
40; 35
SECONDARY
Number of Participants With Any Revascularization
53; 56
SECONDARY
Number of Participants With Definite or Probable Stent Thrombosis
30; 26
SECONDARY
Procedural Complications (Post-procedural Myocardial Infarction and Post-procedural Bleeding)
22; 15
SECONDARY
Device-oriented Composite Endpoint of Target Lesion Failure Will be Used as a Secondary Outcome
51; 45
SECONDARY
Number of Participants With Target Lesion Revascularization (TLR)
40; 47
SECONDARY
Number of Participants With Non-Target Revascularization
60; 69
SECONDARY
Number of Participants With Non-Target Revascularization
60; 69
SECONDARY
Patient-oriented (for Target Lesion Failure) Composite Endpoints Will be Used as Secondary Outcomes as Proposed by Cutlip et al, and as Recommended in the Draft FDA Guidance for Industry Statement.
127; 127
SECONDARY
Device-oriented (for Target Lesion Failure) Composite Endpoints Will be Used as Secondary Outcomes as Proposed by Cutlip et al, and as Recommended in the Draft FDA Guidance for Industry Statement.
95; 94
SECONDARY
Number of Participants With Stroke
12; 10
SECONDARY
Quality Adjusted Life Years of DES Relative to BMS
0.467; 0.503
SECONDARY
Quality Adjusted Life Years for Subgroups of Patients
-0.03; -0.04; -0.03; 0.03; 0.02; 0.04
SECONDARY
In Patients Who Clinically Require Follow-up Angiography, Two Angiographic Endpoints Will be Assessed: (a) In-segment Binary Restenosis and (b) Angiographic Late In-segment Luminal Loss.
1.05; 0.96

Summary

Patients who have undergone coronary bypass surgery have had a vein removed from the leg and implanted in the chest to "bypass" blockages in the coronary arteries. These veins are called saphenous vein grafts or SVGs. SVGs often develop blockages that can cause chest pain and heart attacks. SVG blockages can be opened by using small balloons and stents (metal coils that keep the artery open). Two types of stents are currently used: bare metal stents (BMS) and drug-eluting stents (DES). Both BMS and DES are made of metal. DES are also coated with a drug that releases into the wall of the blood vessel to prevent scar tissue from forming and re-narrowing the vessel. Both stents have advantages and disadvantages: DES require taking special blood thinners (called thienopyridines, such as clopidogrel or prasugrel) longer than bare metal stent and could have more bleeding but are also less likely to renarrow. Both BMS and DES are routinely being used in SVGs, but it is not known which one is better. Neither bare metal (except for an outdated model) nor drug-eluting stents are FDA approved for use in SVGs. The purpose of CSP#571 is to compare the outcomes after DES vs. BMS use in SVGs. In CSP#571 patients who need stenting of SVG blockages will be randomized to receive DES or BMS in a 1:1 ratio. Per standard practice, patients will receive 12 months of an open label thienopyridine if they have acute coronary syndrome (ACS), or if they have another clinical reason for needing the medication. Patients without ACS who receive DES also need to take 12 months of a thienopyridine whether or not they are in the study, but non-ACS patients who receive a BMS do not. In order to make sure patients do not know which stent they received, non-ACS patients who received BMS will receive 1 month of open label thienopyridine followed by 11 months of blinded placebo, while those who received DES will receive 1 month of open label thienopyridine followed by 11 months of blinded clopidogrel, which is a thienopyridine. All study patients will be followed in the clinic for at least 1 year after their stenting procedure to see if there is a difference in the rate of cardiac death, heart attack, or any procedure that is required in order to increase the flow of blood to and from the heart between the BMS and DES groups.

Eligibility Criteria

Inclusion Criteria

  • Age 18 years
  • Need for percutaneous coronary intervention of a 50-99% de novo SVG lesion that is between 2.25 and 4.5 mm in diameter and that is considered to cause clinical or functional ischemia
  • Intent to use a distal embolic protection device
  • Agrees to participate and to take prescribed medications as instructed
  • Has provided informed consent and agrees to participate

Exclusion Criteria

  • Planned non-cardiac surgery within the following 12 months
  • Presentation with an ST-segment elevation acute myocardial infarction
  • Target SVG is the last remaining vessel or is the "left main" equivalent
  • Any previous percutaneous treatment of the target lesion (with balloon angioplasty, stent, intravascular brachytherapy etc)
  • Any previous percutaneous treatment of the target vessel (of a lesion different than the target lesion) within the prior 12 months
  • Hemorrhagic diatheses, or refusal to receive blood transfusions
  • Warfarin administration required for the next 12 months and patient considered to be at high risk of bleeding with triple anticoagulation/antiplatelet therapy
  • Recent positive pregnancy test, breast-feeding, or possibility of a future pregnancy (defined as no prior hysterectomy or as <5 years elapsing since last menstrual period)
  • Coexisting conditions that limit life expectancy to less than 12 months
  • History of an allergic reaction or significant sensitivity to drugs such as sirolimus, paclitaxel, zotarolimus, or everolimus included in various DES. History of an allergic reaction or significant sensitivity to L-605 cobalt chromium alloy (cobalt, silicon, chromium, tungsten, manganese, iron, nickel), F562 cobalt chromium alloy (cobalt, chromium, nickel), 316L surgical stainless steel (iron, chromium, nickel, and molybdenum), or MP35N cobalt-based alloy (cobalt, nickel, chromium, molybdenum, titanium, iron, silicon, and manganese), or components of the platinum chromium alloy stent.
  • Allergy to clopidogrel in patients who do not present with an acute coronary syndrome (ACS), where ACS is defined as cardiac ischemic symptoms occurring at rest and 1 of the following 3 criteria: electrocardiographic changes suggestive of ischemia (ST-segment elevation or depression 1 mm in 2 contiguous leads, or new left bundle branch block, or posterior myocardial infarction); positive biomarker indicating myocardial necrosis (troponin I or T or creatine kinase-MB greater than the upper limit of normal); or coronary revascularization performed during hospitalization triggered by the cardiac ischemic symptoms
  • Participating in another interventional randomized trial (required condition for all CSP studies) for which dual enrollment with DIVA is not approved
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01121224). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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