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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01121224
Recruitment Status : Completed
First Posted : May 12, 2010
Results First Posted : February 1, 2018
Last Update Posted : June 11, 2019
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

Brief 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 Neither bare metal (except for an outdated model) nor drug-eluting stents are FDA approved for use in SVGs.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.


Condition or disease Intervention/treatment Phase
Saphenous Vein Graft Atherosclerosis Device: Bare Metal Stent Device: Drug-Eluting Stent Drug: Blinded clopidogrel Drug: Placebo Drug: Thienopyridine (open-label) Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 597 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: CSP #571 - Drug-eluting Stents vs. Bare Metal Stents in Saphenous Vein Graft Angioplasty (DIVA)
Actual Study Start Date : January 11, 2012
Actual Primary Completion Date : December 31, 2016
Actual Study Completion Date : December 31, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Angioplasty

Arm Intervention/treatment
Active Comparator: BMS Group
Patients who receive a bare metal stent in the saphenous vein graft target lesion(s).
Device: Bare Metal Stent
Patients receive one or more bare metal stents in the saphenous vein graft target lesion.
Other Name: BMS

Drug: Placebo
For non-ACS patients with no other clinical indication for open-label thienopyridine who receive only BMS.

Drug: Thienopyridine (open-label)
For ACS patients who receive BMS or DES in their saphenous vein graft or patients for whom there is another clinical indication for open-label thienopyridine. Also for patients who receive a DES in a non-target lesion.

Experimental: DES Group
Patients who receive a drug-eluting stent in the saphenous vein graft target lesion(s).
Device: Drug-Eluting Stent
Patients receive one or more drug-eluting stents in the saphenous vein graft target lesion.
Other Name: DES

Drug: Blinded clopidogrel
For non-ACS patients with no other clinical indication for open-label thienopyridine who receive one or more DES in the target lesion.
Other Name: Plavix

Drug: Thienopyridine (open-label)
For ACS patients who receive BMS or DES in their saphenous vein graft or patients for whom there is another clinical indication for open-label thienopyridine. Also for patients who receive a DES in a non-target lesion.




Primary Outcome Measures :
  1. Number of Participants With Target Vessel Failure (TVF), Defined as the Composite of Cardiac Death [ Time Frame: 12 months ]
  2. Number of Participants With Target Vessel Failure (TVF), Defined as the Target Vessel Myocardial Infarction [ Time Frame: 12 months ]
  3. Number of Participants With Target Vessel Failure (TVF), Defined as the Target Vessel Revascularization [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Incremental Cost-effectiveness of DES Relative to BMS [ Time Frame: 12 months ]
  2. Procedural Success [ Time Frame: Discharge from Index Hospitalization (an average of 36 hours) ]
    The procedural success rate and the incidence of post-procedural myocardial infarction and post-procedural GUSTO moderate or severe bleeding were compared between the DES and BMS groups by the difference between two independent proportions. Cumulative incidence curves and stratified log-rank tests were used to compare the two stent groups on the incidence of the secondary clinical outcomes listed above. When appropriate, competing risks analyses with plots of cumulative incidence curves and comparisons of cumulative incidences with Gray's test and Fine and Gray's methods were done. Proportional hazards regression for sub-distributions of competing risks were also done. SAS 9.2 (TS2M3; SAS Institute, Cary, NC, USA) and R version 3.4.4 were used for the analyses.

  3. Number of Participant Deaths (All Cause and Cardiac). All Deaths Will be Considered Cardiac Unless an Unequivocal Non-cardiac Cause Can be Established. [ Time Frame: Entire Duration of Follow-up (median 2.7 years) ]
  4. Number of Participants With Myocardial Infarction (MI) [ Time Frame: Entire Duration of Follow-up (median 2.7 years) ]
  5. Number of Participants With Definite Stent Thrombosis as Defined Using the Academic Research Consortium (ARC) Definition [ Time Frame: 12 months ]

    Definite stent thrombosis will be considered to have occurred by either angiographic or pathologic confirmation.

    Angiographic Confirmation of Stent Thrombosis will be defined as the presence of thrombus originating in a study stent, or in the segment 5mm proximal or distal to the stent AND fulfillment of at least one of the following 5 criteria within a 48 hour time window:

    • Acute onset of ischemic symptoms at rest
    • New ischemic ECG changes suggestive of acute ischemia
    • Rise and fall of cardiac biomarkers
    • Nonocclusive intracoronary thrombus seen in multiple projections, or persistence of contrast material within the lumen, or a visible embolization of intraluminal material downstream
    • Occlusive intracoronary thrombus Pathological Confirmation of stent thrombosis will be defined as evidence of recent thrombus with the stent determined at autopsy or via examination of tissue retrieved following thrombectomy.

  6. Number of Participants With Target Vessel Revascularization (TVR) [ Time Frame: Entire Duration of Follow-up (median 2.7 years) ]
  7. Patient-Oriented Composite Endpoint Will be Used as Secondary Outcome [ Time Frame: 12 months ]

    The patient-oriented composite endpoint is defined as the composite of all-cause death, any myocardial infarction and target vessel revascularization.

    Target vessel (SVG) revascularization (TVR) will be defined as any repeat percutaneous intervention or surgical bypass of any segment of the target SVG and the native coronary vessel distal to the SVG anastomosis. Non-target vessel revascularization will be defined as any repeat percutaneous intervention or surgical bypass of any SVG or any native coronary vessel apart from the target SVG and the native coronary artery supplied by the target SVG.


  8. 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. [ Time Frame: 12 months ]
  9. Number of Participants With Stroke [ Time Frame: 12 months ]
  10. 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. [ Time Frame: 12 months ]
  11. In-stent Neointima Proliferation as Measured by Intravascular Ultrasonography [ Time Frame: 12 months ]
  12. Number of Participants With Target Lesion Revascularization (TLR) [ Time Frame: 12 months ]
  13. Number of Participants With Target Vessel Myocardial Infarction [ Time Frame: Entire Duration of Follow-up (median 2.7 years) ]
  14. Number of Participants With Any Revascularization [ Time Frame: 12 months ]
  15. Number of Participants With Definite or Probable Stent Thrombosis [ Time Frame: Entire Duration of Follow-up (median 2.7 years) ]

    Definite stent thrombosis will be considered to have occurred by either angiographic or pathologic confirmation.

    Probable Stent Thrombosis will clinically be considered to have occurred after index Saphenous Vein aortocoronary bypass Graft (SVG) stenting (the Percutaneous Coronary Intervention (PCI) immediately after randomization) in the following cases: a) any unexplained death within the first 30 days OR b) Irrespective of the time after the index procedure, any MI which is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis and in the absence of any other obvious cause.


  16. Procedural Complications (Post-procedural Myocardial Infarction and Post-procedural Bleeding) [ Time Frame: Discharge from Index Hospitalization (an average of 36 hours) ]
    Incidence of post-procedural myocardial infarction and post-procedural GUSTO moderate or severe bleeding were compared between the DES and BMS groups by the difference between two independent proportions. Cumulative incidence curves and stratified log-rank tests were used to compare the two stent groups on the incidence of the secondary clinical outcomes listed above. When appropriate, competing risks analyses with plots of cumulative incidence curves and comparisons of cumulative incidences with Gray's test and Fine and Gray's methods were done. Proportional hazards regression for sub-distributions of competing risks were also done. SAS 9.2 (TS2M3; SAS Institute, Cary, NC, USA) and R version 3.4.4 were used for the analyses.

  17. Device-oriented Composite Endpoint of Target Lesion Failure Will be Used as a Secondary Outcome [ Time Frame: 12 months ]

    The Device-oriented composite endpoint of Target lesion failure is defined as the composite of cardiac or unknown death, target vessel myocardial infarction, and target lesion revascularization.

    Target lesion revascularization (TLR) will be defined as any repeat percutaneous intervention of the target SVG lesion or bypass surgery of the target SVG lesion performed for restenosis or other complication of the target lesion. The target lesion will be defined as the treated SVG segment from 5 mm proximal to the stent to 5 mm distal to the stent.


  18. Number of Participants With Target Lesion Revascularization (TLR) [ Time Frame: Entire Duration of Follow-up (median 2.7 years) ]
  19. Number of Participants With Non-Target Revascularization [ Time Frame: 12 months ]
  20. Number of Participants With Non-Target Revascularization [ Time Frame: Entire Duration of Follow-up (median 2.7 years) ]
  21. 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. [ Time Frame: Entire Duration of Follow-up (median 2.7 years) ]
    The patient-oriented composite endpoint is defined as the composite endpoint of any death, any myocardial infarction, or target vessel revascularization.

  22. 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. [ Time Frame: Entire Duration of Follow-up (median 2.7 years) ]
    The device-oriented composite endpoint for target lesion failure is defined as the composite endpoint of cardiac death, target vessel myocardial infarction, or target lesion revascularization.

  23. Number of Participants With Stroke [ Time Frame: Entire Duration of Follow-up (median 2.7 years) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01121224


Locations
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Sponsors and Collaborators
VA Office of Research and Development
Investigators
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Study Chair: Emmanouil S Brilakis, MD PhD VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
Study Chair: Subhash Banerjee, MD VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT01121224    
Other Study ID Numbers: 571
First Posted: May 12, 2010    Key Record Dates
Results First Posted: February 1, 2018
Last Update Posted: June 11, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Keywords provided by VA Office of Research and Development:
Saphenous vein graft
Percutaneous coronary intervention
Stents
Additional relevant MeSH terms:
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Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Clopidogrel
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs