COBRA REDUCE Randomized Control Trial

6-Month Interim Results1‡

World’s First and Only 14-Day DAPT Study

COBRA REDUCE is a global, randomized control trial evaluating ultra-short, 14-day dual antiplatelet therapy (DAPT) in percutaneous coronary intervention (PCI) patients at High Bleeding Risk (HBR).2*
The COBRA PzF NanoCoated Coronary Stent is not currently approved or indicated for high bleeding risk patients with 14-day DAPT.

COBRA Reduce 14 DAY DAPT Under Clinical Trial

Patients with ischemic symptoms (stable or
unstable angina or NSTEMI+ without thrombosis of the target lesion on coronary angiography) or evidence of myocardial ischemia undergoing PCI

Receiving oral anticoagulation currently or with a new indication for oral anticoagulation

Patients with ischemic symptoms (stable or unstable angina or NSTEMI+ without thrombosis of the target lesion on coronary angiography) or evidence of myocardial ischemia undergoing PCI

Receiving oral anticoagulation currently or with a new indication for oral anticoagulation

COBRA PzF NCS
+ 14-Day DAPT

DES
+ 3 or 6-Month DAPT

COBRA PzF NCS + 14-Day DAPT

DES + 3 or 6-Month DAPT

COBRA REDUCE Offers Promising New Evidence in a Highly Complex, High Bleeding Risk Patient Population With Just 14-Days DAPT

6-Month Interim Results Presented at TCT Connect 2020

We are pleased to provide interim data available on the COBRA PzF NCS arm. Complete data on both study arms will be provided once the primary endpoint analysis is complete.

It is encouraging to see that the COBRA stent demonstrated a very low stent thrombosis rate with just 14 days in this high-risk patient population.

—Roxana Mehran, MD

COBRA REDUCE HBR Criteria

Ultra HBR Patient Population With Highly Complex Lesions

COBRA REDUCE HBR Criteria

Ultra HBR Patient Population With Highly Complex Lesions

COBRA Patient Profile

100% NOAC/VKA (90%-Afib Diag) | 36% Diabetes | 20% Bifurcations | 68% B2/C Lesions

COBRA Patient Profile

100% NOAC/VKA (90%-Afib Diag) | 36% Diabetes | 20% Bifurcations | 68% B2/C Lesions

COBRA Delivers Strong Ischemic Performance With Just 14-Days DAPT

6-Month Results

2.3% Cardiac Death | 2.8% MI | .06% Def/Prob ST | 1.3% Stroke | 3.7% ID-TLR

COBRA Delivers Strong Ischemic Performance With Just 14-Days DAPT

2.3% Cardiac Death | 2.8% MI | .06% Def/Prob ST | 1.3% Stroke | 3.7% ID-TLR

Low Overall Bleeding Events Across All BARC Classes

6-Month Results

BARC 2-5 (After Randomized) - 11.7% | BARC 3-5 (After 14 Days) - 3.9% | BARC 3-5 (After Randomized) - 6.8% | BARC 1-5 (After Randomized) - 13.0%

Low Overall Bleeding Events Across All BARC Classes

BARC 2-5 (After Randomized) - 11.7% | BARC 3-5 (After 14 Days) - 3.9% | BARC 3-5 (After Randomized) - 6.8% | BARC 1-5 (After Randomized) - 13.0%

Complete 6-Month Follow-Up & 12-Month Data Coming Soon

COBRA REDUCE’s final co-primary endpoint analysis at 6 months and secondary endpoints, including composite of all-cause death, cardiac death, MI, ischemia-driven TLR, definite and probable stent thrombosis and ischemic stroke at 12 months are expected to be revealed in early 2021.

  • COBRA REDUCE Trial Design

    Study Hypothesis: In patients undergoing coronary intervention who are also receiving OAC, 14 days of DAPT after stenting with COBRA PzF NCS provides superior outcome in bleeding (BARC class ≥ 2) and non-inferior outcomes in composite of death, MI, stent thrombosis (definite and probable), and ischemic stroke versus 3 or 6 months of DAPT after stenting with standard, FDA-approved DES.

    Superiority in Bleeding Reduction

    (BARC class ≥ 2)

    Non-Inferior Outcomes for Thromboembolic Events

    (composite of death, MI, stent thrombosis, and ischemic stroke)

    Study Participants: PCI Patients at High Bleeding Risk 

    • High bleeding risk patients (>18 years of age) undergoing coronary intervention
    • With ischemic symptoms (stable or unstable angina or NSTEMI without thrombosis of the target lesion on coronary angiography) or evidence of myocardial ischemia in the presence of ≥ 50% de novo stenosis located in native coronary vessels (maximum 2 lesions in 1 or 2 separate vessels)
    • On oral anticoagulation with a non-vitamin K oral anticoagulant (NOAC) or a vitamin K antagonist

    Co-Primary Endpoints

    • BARC class ≥ 2 bleeding at 6 months post‐randomization
    • Composite endpoint of all-cause death, myocardial infarction, definite and probable stent thrombosis, or ischemic stroke at 6 months post‐randomization

    Secondary Endpoints

    • Composite of all-cause death, myocardial infarction, definite and probable stent thrombosis, ischemia‐driven target lesion revascularization or ischemic stroke at 12 months post‐randomization
    • Composite of cardiac death and myocardial infarction at 12 months
    • Ischemia-driven target lesion revascularization at 12 months
    • Definite and probable stent thrombosis at 12 months
    • Ischemic stroke at 12 months
    • BARC class 3‐5 bleeding at 6 months
    • TIMI major bleeding, TIMI major and minor bleeding at 6 months
    • Health economic utilities (total cardiovascular and bleeding related costs with cost-effectiveness based on events avoided)

    The data will only be collected from participating sites in the US, France, and Switzerland.

    Exclusion Criteria

    1. Cardiogenic shock
    2. Target lesion located in left main trunk
    3. Bifurcation interventions with a planned 2‐stent strategy
    4. Vessel size too small for implantation of a 2.5 mm stent by visual estimation
    5. Patients requiring staging PCI procedure within 6 months after the index procedure
    6. Patients requiring DAPT for more than 2 weeks after the index procedure
    7. Contraindications or allergy to cobalt, chromium, platinum, Polyzene‐F, Everolimus, Zotarolimus or the inability to take triple therapy for at least 6 months
    8. Relevant hematologic deviations: platelet count < 100 x 109 cells/L or > 600 x 109 cells/L
    9. Active bleeding, bleeding diathesis, recent trauma or major surgery in the last month, history of intracranial bleeding or structural abnormalities, suspected aortic dissection
      Malignancies or other comorbid conditions with life expectancy less than 12 months or that may result in protocol non‐compliance
    10. Pregnancy, present (positive pregnancy test), suspected or planned, breastfeeding
      Known allergy or intolerance to the study medications: aspirin, clopidogrel, Coumadin and its derivatives
      Patient’s inability to fully cooperate with the study protocol
  • High Bleeding Risk & PCI

    Approximately 1 in 5 Patients Is at High Risk of Bleeding Following PCI2

    Complications from bleeding occur more frequently than myocardial infarction and have a greater impact on mortality.3

    • The bleeding risk of a PCI patient increases considerably when you factor in major criteria such as use of oral anticoagulants, recent stroke, or nondeferrable surgery post-PCI.1
    • Defining bleeding risk is the first step toward addressing clinically meaningful risks and benefits in patients at HBR undergoing PCI.1

    Identify HBR Patients Prior to PCI

    Patients are considered HBR if they meet at least 1 major or 2 minor criteria per ARC-HBR guidelines.1

    MAJOR HBR CRITERIA

    Spontaneous bleeding requiring hospitalization or transfusion in the past 6 months or at any time if recurrent

    Active malignancy within the past 12 months

    Major surgery or major trauma within 30 days before PCI


    Nondeferrable major surgery on DAPT

    Hemoglobin < 11 g/dL for both men and women

    Moderate or severe baseline thrombocytopenia§ (platelet count
    < 100 × 109/L)

    Liver cirrhosis with portal hypertension

    Anticipated use of long-term oral anticoagulation

    Severe or end-stage chronic kidney disease (CKD) (eGFR < 30 mL/min)

    Chronic bleeding diathesis

    Previous spontaneous intracranial hemorrhage (ICH) at any time, previous traumatic ICH within the past 12 months, presence of a brain arteriovenous malformation (bAVM), moderate or severe ischemic stroke§ within the past 6 months

    MINOR HBR CRITERIA

    Age ≥ 75 years

    Moderate CKD (eGFR 30-59 mL/min)

    Hemoglobin 11.0-11.9 g/dL for women and 11.0-12.9 g/dL for men

    Long-term use of oral nonsteroidal anti-inflammatory drugs (NSAIDs) or steroids

    Spontaneous bleeding requiring hospitalization or transfusion in the previous 12 months not meeting the major criterion

    Any ischemic stroke at any time not meeting the major criterion

    The Academic Research Consortium for High Bleeding Risk (ARC-HBR) group has defined HBR as a BARC 3 or 5 bleeding risk of at least 4% at 1 year or an ICH risk of at least 1% at 1 year.*

    This tool is for illustrative purposes only and does not represent a diagnosis.

    Adapted from Urban P, Mehran R, Colleran R, et al. Defining high bleeding risk in patients undergoing percutaneous coronary intervention: a consensus document from the Academic Research Consortium for High Bleeding Risk. Eur Heart J. 2019;40(31):2632-2653.
    bAVM indicates brain arteriovenous malformation; CKD, chronic kidney disease; CNS, central nervous system; DAPT, dual antiplatelet therapy; eGFR, estimated glomerular filtration rate; HBR, high bleeding risk; ICH, intracranial hemorrhage; NSAID, nonsteroidal anti-inflammatory drug; OAC, oral anticoagulation and PCI, percutaneous coronary intervention.
    *This excludes vascular protection doses.
    †Baseline thrombocytopenia is defined as thrombocytopenia before PCI.
    ‡Active malignancy is defined as diagnosis within 12 months and/or ongoing requirement for treatment (including surgery, chemotherapy, or radiotherapy).
    §National Institutes of Health Stroke Scale score ≥ 5

  • Interim Data
    A Highly Complex, High Bleeding Risk Patient Population
    Baseline Patient Characteristics COBRA + 14-Day DAPT(N = 495)
    Age/Years 74.8 ± 8.7
    Female Gender 28%
    Diabetes 36%
    Hypertension 91%
    Current Smoker 9%
    Prior Heart Failure 28%
    Previous MI 14%
    Previous Stroke 13%
    Peripheral Vascular Disease 13%
    Over 90% of Study Patients Presented with Atrial Fibrillation
    Baseline Patient Characteristics COBRA + 14-Day DAPT(N = 495)
    Indication for PCI
    Acute Coronary Syndrome 27%
    Chronic Coronary Syndrome 73%
    Access Site
    Radial 68%
    Femoral 32%
    Indication for OAC
    Artrial Fibrillation 92%
    Mechanical Heart Valve 2%
    VTE/PE 5%
    Other 2%
    VKA 31%
    Dabigatran 5%
    Rivaroxaban 27%
    Apixaban 33%
    Edoxaban 4%
    Study Patients Had High Lesion Complexity and Bifurcations
    Baseline Patient Characteristics COBRA + 14-Day DAPT(N = 495)
    Target Vessel
    LAD 46%
    RCA 30%
    Left Circumflex 23%
    Left Main 0.2%
    Lesion Complexity, B2/C 68%
    Bifurcation 20%
    Chronic Total Occulation 1%
    Reference Vessel Diameter (mm) 2.89 ± 0.50
    Diameter Stenosis, pre (%) 63.5 ± 11.7
    Lesion Length (mm) 14.96 ± 8.98
    Maximum Balloon Pressure, atm 15.56 ± 4.06
    Diameter Stenosis, post (%) 21.2 ± 9.9
    Procedural Success 98.5%
    COBRA Delivered a Strong Thromboembolic Performance at 14 Days of DAPT
    6-Month Results
    Event COBRA + 14-Day DAPT
    Composite of Death, MI, Stent Thrombosis, Ischemic Stroke (Co-Primary Endpoint) 7.7%
    Death 4.1%
    Cardiac Death 2.3%
    MI 2.8%
    Def/Prob ST 0.6%
    Ischemic Stroke 1.3%
    ID-TLR 3.7%
    BARC 2-5 Bleeding (After 14 Days) (Co-Primary Endpoint) 7.5%
    BARC 2-5 Bleeding (After Randomization) 11.7%
    BARC 3-5 Days (After 14 Days) 3.9%
    BARC 3-5 Days (After Randomization) 6.8%
    BARC 1-5 Days (After Randomization) 13.0%

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Project Management: ISAResearch Centre | Deutsches Herzzentrum, Munich, Germany
Contributing Countries: US | Switzerland | France | Germany | Belgium | Denmark | Italy | Latvia


The COBRA PzF NanoCoated Coronary Stent is not currently approved or indicated for high bleeding risk patients with 14-day DAPT.
2016 ACC/AHA Guidelines for Duration of DAPT in Patients with Coronary Artery Disease.
Indications, Contraindications, Warnings & Precautions
*Patients on Oral Anticoagulants
†DAPT +OAC
‡Data presented reflects six-month follow-up data available as of October 15, 2020. Six-month follow-up data for N = 15 patients is pending. Readers should be aware that any aspect of the research, including the results and conclusions, may change as a result of the pending data and subsequent peer review.
References:
  1. Byrne R. Randomized Trial of COBRA PzF Stenting to REDUCE Duration of Triple Therapy (COBRA-REDUCE). Presented at: TCT 2020; October 15, 2020
  2. Urban P, Mehran R, Colleran R, et al. Defining high bleeding risk in patients undergoing percutaneous coronary intervention: a consensus document from the Academic Research Consortium for High Bleeding Risk. Eur Heart J. 2019;40(31):2632-2653.
  3. Généreux P, Giustino G, Witzenbichler B, et al. Incidence, Predictors, and Impact of Post-Discharge Bleeding After Percutaneous Coronary Intervention. JACC Cardiovasc Interv. 2015;66(9):1036-1045.