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Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX (MATRIX)

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: NCT01433627
Recruitment Status : Unknown
Verified January 2015 by Italian Society of Invasive Cardiology.
Recruitment status was:  Active, not recruiting
First Posted : September 14, 2011
Last Update Posted : January 29, 2015
Sponsor:
Collaborator:
Eustrategy
Information provided by (Responsible Party):
Italian Society of Invasive Cardiology

Tracking Information
First Submitted Date  ICMJE September 12, 2011
First Posted Date  ICMJE September 14, 2011
Last Update Posted Date January 29, 2015
Study Start Date  ICMJE October 2011
Actual Primary Completion Date November 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 13, 2011)
  • the composite of Death, non-fatal myocardial infarction or stroke [ Time Frame: 30 days ]
    To demonstrate in ACS patients undergoing an early invasive management, i.e. diagnostic coronary angiogram+PCI or ad hoc planned PCI that trans-radial intervention as compared to femoral access site is associated to lower rate of the composite endpoint of death, MI or stroke within the first 30 days after randomization.
  • The composite of death, non-fatal myocardial infarction or stroke [ Time Frame: 30 days ]
    To demonstrate that in an ACS patients with an intended PCI treatment strategy or in whom upstream treatment was felt necessary by local investigators the use of bivalirudin as compared to unfractionated heparin (UFH) plus or minus Glycoprotein IIb/IIIa inhibitor (GPI) is associated to lower rate of the composite endpoint of death, MI or stroke within the first 30 days after randomization.
  • Death, non-fatal myocardial infarction, stroke, stent thrombosis or BARC-defined type 3 or 5 bleedings [ Time Frame: 30 days ]
    The primary hypothesis of this sub-randomization is that prolonged post-intervention bivalirudin infusion (long bivalirudin arm) will be superior to peri-PCI bivalirudin infusion only (short bivalirudin arm) with respect to the net composite outcomes consisting of any death, MI, stroke, stent thrombosis or BARC-defined type 3 and 5 bleeding events within 30 days.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 13, 2011)
  • the composite endpoint of death, MI, stroke or BARC-defined type 3 and 5 major bleeding complications [ Time Frame: 30 days ]
    Key secondary objective: To demonstrate that trans-radial intervention as compared to femoral access site is associated to lower rate of the composite endpoint of death, MI, stroke or BARC-defined type 3 and 5 major bleeding complications within the first 30 days after randomization.
  • Death, non-fatal MI, stroke or BARC-defined type 3 and 5 major bleeding [ Time Frame: 30 days ]
    To demonstrate that use of bivalirudin as compared to unfractionated heparin (UFH) plus or minus Glycoprotein IIb/IIIa inhibitor (GPI) is associated to lower rate of the composite endpoint of death, MI, stroke or BARC-defined type 3 and 5 major bleeding complications within the first 30 days after randomization.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX
Official Title  ICMJE Phase IIIb Study Minimizing Adverse Haemmhorragic Events by TRansradial Access Site and Systemic Implementation of angioX (MATRIX)
Brief Summary This protocol describes a study to compare intended trans-radial versus trans-femoral intervention and bivalirudin monotherapy versus current European standard of care consisting of unfractionated heparin (UFH) plus provisional use of glycoprotein IIb/IIIa inhibition via the use of one of the three available agents on the market (e.g. abciximab, tirofiban or eptifibatide) in patients (≥18 years) with ACS, that are intended for an invasive management strategy. This study will be conducted in compliance with Good Clinical Practices (GCP) including the Declaration of Helsinki and all applicable regulatory requirements.
Detailed Description

The use of combined antithrombotic therapies over the last two decades has decreased the risk of a heart attack after percutaneous coronary intervention substantially but has also been associated with a significant increase in bleeding risk. Therapies or strategies that maintain the benefits seen with currently available antithrombotic therapies but which have lower bleeding risk are therefore of great clinical importance. Indeed, major bleeding is currently the most common non-cardiac complication of therapy for patients with coronary artery disease who have undergone percutaneous coronary intervention (PCI).

Bleeding in patients with acute coronary syndrome (ACS) is associated with an increased risk of long term mortality and morbidity, and this relationship is currently thought to be causal. Therefore' reducing the frequency of bleeding events while maintaining efficacy is an important goal in the management of patients with ACS. The most common site of bleeding in invasively managed patients with ACS is at the femoral artery puncture site used for heart catheterization

The MATRIX study is a multi-centre, prospective, randomised, open-label, 2 by 2 factorial comparison of trans-radial vs. trans-femoral intervention and bivalirudin vs. unfractionated heparin and provisional use of glycoprotein IIb/IIIa inhibitor.

Objectives:

  1. To demonstrate that trans-radial intervention as compared to femoral access site is associated to lower rate of the composite endpoint of death, MI or stroke within the first 30 days after randomization in acute coronary syndrome patients undergoing early invasive management.
  2. To demonstrate that bivalirudin infusion as compared to standard of care therapy consisting of unfractionated heparin and provisional use of glycoprotein IIb/IIIa inhibitors are associated to lower rate of the composite endpoint of death, MI or stroke within the first 30 days after randomization in acute coronary syndrome patients undergoing early invasive management.

Patients randomly assigned to receive bivalirudin will be randomized to stop bivalirudin infusion at the end of PCI or to prolong bivalirudin at an infusion rate of 0.25 mg/kg/hour for at least 6 hours after completion of PCI. The primary hypothesis in this sub-randomization is that prolonged post-intervention bivalirudin infusion will be superior to no bivalirudin post-PCI infusion with respect to the net composite outcome consisting of any death, MI, stroke, urgent TVR, stent thrombosis and BARC-defined type 3 and 5 bleeding events within 30 days. Secondary objectives for the sub-randomization of prolonged bivalirudin versus no post-PCI infusion in the bivalirudin group will consist of each component of the primary composite endpoint through the entire follow-up duration

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Coronary Syndromes
  • STEMI
  • NSTEMI
Intervention  ICMJE
  • Other: trans-radial and short-term bivalirudin
    trans-radial intervention followed by Bivalirudin given immediately upon enrolment as bolus of 0.75 mg/kg followed immediately by an infusion of 1.75 mg/kg/h. This infusion should be run continuously until completion of PCI at which time the infusion should be stopped.
    Other Name: Access site selection and drug administration
  • Other: trans-radial and long-term bivalirudin infusion

    Trans-radial intervention: will be performed according to institutional guidelines and established local practice.

    Bivalirudin: given immediately upon enrolment as bolus of 0.75 mg/kg followed immediately by an infusion of 1.75 mg/kg/h. This infusion should be run continuously until completion of PCI at which time the infusion should be reduced to a dose of 0.25 mg/kg/h for at least 6 hours. An optional higher-dose infusion of 1.75 mg/kg/h is also permitted for up to 4 hours in the prolonged infusion arm but prohibited in the short bivalirudin group.

    Other Name: access site selection and drug administration
  • Other: trans-radial and standard of care pharmacology
    Unfractionated heparin (UFH) (100 IU/kg with no glycoprotein IIb/IIIa inhibitor (GPI) and 60 IU/kg with a GPI); +/- routine or bail out eptifibatide (two 180 μg /kg boluses with a 10 minute interval followed by an infusion of 2.0 μg /kg/min for 72-96 hours) or tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18 to 24 hours) or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours (maximum dose, 10 μg/min).
    Other Name: access site and drug administration
  • Other: Trans-femoral and Short-term bivalirudin

    Trans-femoral intervention: will be performed according to institutional guidelines and established local practice. Access closure devices are allowed as per local practice.

    Bivalirudin will be given immediately upon enrolment as bolus of 0.75 mg/kg followed immediately by an infusion of 1.75 mg/kg/h. This infusion should be run continuously until completion of PCI.

    Other Name: access site selection and drug administration
  • Other: trans-femoral and long-term bivalirudin infusion

    Trans-femoral intervention: will be performed according to institutional guidelines and established local practice. Access closure devices are allowed as per local practice.

    Bivalirudin will be given immediately upon enrolment as bolus of 0.75 mg/kg followed immediately by an infusion of 1.75 mg/kg/h. This infusion should be run continuously until completion of PCI at which time the infusion should be reduced to a dose of 0.25 mg/kg/h for at least 6 hours. An optional higher-dose infusion of 1.75 mg/kg/h is also permitted for up to 4 hours in the prolonged infusion arm but prohibited in the short bivalirudin group.

    Other Name: access site selection and drug administration
  • Other: trans-femoral and standard of care pharmacology
    Trans-femoral intervention: will be performed according to institutional guidelines and established local practice. Access closure devices are allowed as per local practice. Unfractionated heparin (UFH) (100 IU/kg with no glycoprotein IIb/IIIa inhibitor (GPI) and 60 IU/kg with a GPI); +/- routine or bail out eptifibatide (two 180 μg /kg boluses with a 10 minute interval followed by an infusion of 2.0 μg /kg/min for 72-96 hours) or tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18 to 24 hours) or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours (maximum dose, 10 μg/min).
    Other Name: access site selection and drug administration
Study Arms  ICMJE
  • Experimental: trans-radial and short-term Bivalirudin
    Patients will be randomized to receive a trans-radial intervention and concomitant bivalirudin infusion. bivalirudin will be stopped at the end of PCI.
    Intervention: Other: trans-radial and short-term bivalirudin
  • Experimental: trans-radial and long-term bivalirudin

    Trans-radial intervention: will be performed according to institutional guidelines and established local practice.

    Bivalirudin: given immediately upon enrolment as bolus of 0.75 mg/kg followed immediately by an infusion of 1.75 mg/kg/h. This infusion should be run continuously until completion of PCI at which time the infusion should be reduced to a dose of 0.25 mg/kg/h for at least 6 hours. An optional higher-dose infusion of 1.75 mg/kg/h is also permitted for up to 4 hours in the prolonged infusion arm but prohibited in the short bivalirudin group.

    Intervention: Other: trans-radial and long-term bivalirudin infusion
  • Experimental: trans-radial and standard of care pharmacology

    Trans-radial intervention: will be performed according to institutional guidelines and established local practice.

    unfractionated heparin (UFH) which may be followed by the addition of a glycoprotein IIb/IIIa inhibitor

    Intervention: Other: trans-radial and standard of care pharmacology
  • Experimental: trans-femoral and short-term bivalirudin

    Trans-femoral intervention: will be performed according to institutional guidelines and established local practice. Access closure devices are allowed as per local practice.

    Bivalirudin will be given immediately upon enrolment as bolus of 0.75 mg/kg followed immediately by an infusion of 1.75 mg/kg/h. This infusion should be run continuously until completion of PCI.

    Intervention: Other: Trans-femoral and Short-term bivalirudin
  • Experimental: Trans-femoral and long-term bivalirudin

    Trans-femoral intervention: will be performed according to institutional guidelines and established local practice. Access closure devices are allowed as per local practice.

    Bivalirudin will be given immediately upon enrolment as bolus of 0.75 mg/kg followed immediately by an infusion of 1.75 mg/kg/h. This infusion should be run continuously until completion of PCI at which time the infusion should be reduced to a dose of 0.25 mg/kg/h for at least 6 hours. An optional higher-dose infusion of 1.75 mg/kg/h is also permitted for up to 4 hours in the prolonged infusion arm but prohibited in the short bivalirudin group.

    Intervention: Other: trans-femoral and long-term bivalirudin infusion
  • Active Comparator: trans-femoral and standard of care pharmacology
    Trans-femoral intervention: will be performed according to institutional guidelines and established local practice. Access closure devices are allowed as per local practice. Unfractionated heparin (UFH) (100 IU/kg with no glycoprotein IIb/IIIa inhibitor (GPI) and 60 IU/kg with a GPI); +/- routine or bail out eptifibatide (two 180 μg /kg boluses with a 10 minute interval followed by an infusion of 2.0 μg /kg/min for 72-96 hours) or tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18 to 24 hours) or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours (maximum dose, 10 μg/min).
    Intervention: Other: trans-femoral and standard of care pharmacology
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: September 1, 2014)
7200
Original Estimated Enrollment  ICMJE
 (submitted: September 13, 2011)
6800
Estimated Study Completion Date  ICMJE December 2015
Actual Primary Completion Date November 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

NSTEACS definition: Patients with all of the following criteria will be eligible:

  1. history consistent with new, or worsening ischemia, occurring at rest or with minimal activity;
  2. enrollment within 7 days of the most recent symptoms;
  3. planned coronary angiography with possible indication to PCI;
  4. at least 2 of the following criteria: 1. Aged 60 years or older, 2. Troponin T or I or creatine kinase MB above the upper limit of normal; 3. Electrocardiograph changes compatible with ischemia, ie, ST depression of 1 mm or greater in 2 contiguous leads, T-wave inversion more than 3 mm, or any dynamic ST shifts;

STEMI definition: i) chest pain for >20 min with an electrocardiographic ST-segment elevation ≥1 mm in two or more contiguous electrocardiogram (ECG) leads, or with a new left bundle-branch block, or an infero-lateral myocardial infarction (MI) with ST segment depression of ≥1 mm in ≥2 of leads V1-3 with a positive terminal T wave and ii) admission either within 12 h of symptom onset or between 12 and 24 h after onset with evidence of continuing ischemia or previous lytic treatment.

Exclusion Criteria:

  1. Patients who can not give informed consent or have a life expectancy of <30 days
  2. Allergy/intolerance to Bivalirudin or unfractionated heparin.
  3. Stable or silent CAD as indication to coronary angiography
  4. Treatment with LWMH within the past 6 hours
  5. Treatment with any GPI in the previous 3 days
  6. Absolute contraindications or allergy that cannot be pre-medicated to iodinated contrast or to any of the study medications including aspirin or clopidogrel.
  7. Contraindications to angiography, including but not limited to severe peripheral vascular disease.
  8. If it is known pregnant or nursing mothers. Women of child-bearing age will be asked if they are pregnant or think that they may be pregnant.
  9. If it is known a creatinine clearance <30 mL/min or dialysis dependent.
  10. Previous enrollment in this study.
  11. Treatment with other investigational drugs or devices within the 30 days preceding
  12. Randomisation or planned use of other investigational drugs or devices in this trial.
  13. Severe uncontrolled hypertension (defined as persistent systolic blood pressure higher than 220 mmHg despite medical treatment).
  14. Subacute bacterial endocarditis
  15. PCI in the previous 30 days
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries Switzerland
 
Administrative Information
NCT Number  ICMJE NCT01433627
Other Study ID Numbers  ICMJE RFBU 11-I
2011-000430-11 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Italian Society of Invasive Cardiology
Study Sponsor  ICMJE Italian Society of Invasive Cardiology
Collaborators  ICMJE Eustrategy
Investigators  ICMJE
Principal Investigator: Marco Valgimigli, MD PhD Erasmus MC, Thoraxcenter, The Netherlands
PRS Account Italian Society of Invasive Cardiology
Verification Date January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP